Displaying One Session

Exhibition area Poster Display session
Date
18.11.2017
Session Time
13:00 - 14:00
Session Room
Exhibition area
Basic science Poster lunch Poster Display session

3P - Prevalence and genotyping of HPV infection in Jiangsu, a high-risk region for esophageal cancer in China (ID 807)

Presentation Number
3P
Presentation Topic
Basic science
Lecture Time
13:00 - 13:00
Speakers
  • Y. Miao
Authors
  • Y. Miao
  • R. Liu
  • Y. Pu
  • L. Yin
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

An increasing number of studies have found HPV infection in esophageal carcinoma patients recently. However, reported rates of HPV infection as evidenced were divergent by differences in geographic regions of sample origin.

Methods

To detect the HPV status in Huai’an, China, a high-risk area for esophageal cancer (EC), ELISA was used to determine the seropositivity of HPV16/18 in the blood plasma of the high-risk population of Huai’an esophageal cancer. In the high-risk group, 937 volunteers were recruited by cluster sampling from high incident counties for esophageal cancer in Jiangsu during 2009 to 2013. For the patient group, HPV L1 DNA and HPV genotypes were identified in the cancerous tissues of 105 EC patients from the First People's Hospital in Huai’an by nested-PCR and dot blot hybridization.

Results

The results showed that the overall rate of HPV infection in the high-risk group and the patient group was 31.4% and 34.36%, respectively. HPV18/16 covered 77.3% of HPV infection among the high-risk group. In the EC patient group, only HPV18 was detected in cancerous tissues, and the prevalence of infection (24.2%) was integrally higher than most related reports in other areas.

Conclusions

In conclusion, the current study evaluates the prevalence and genotyping of HPV infection in a high-risk population and patients with esophageal cancer in Huai’an, Jiangsu, and HPV18 may be the highest risk subtype of HPV infection in the Jiangsu area.

Legal entity responsible for the study

School of Public Health, Southeast University

Funding

The National Science Foundation of China

Disclosure

All authors have declared no conflicts of interest.

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4P - Ganoderma Lucidum has immunostimulatory and antinflamatory effect in breast cancer patients (ID 1375)

Presentation Number
4P
Presentation Topic
Basic science
Lecture Time
13:00 - 13:00
Speakers
  • R. Othman
Authors
  • R. Othman
  • H. Saeed
  • N. Abdulkader
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

Breast cancer (BC) is the most common cancer among women. A key factor in tumour development is evasion of immune detection therefore, the search for alternative medicines with reduced toxicity towards normal tissues as well as ability to improve function of immune system and targets tumours cells has received growing interest. Ganoderma lucidum (GL) have been demonstrated to possess anti-tumour and immunomodulatory activities. Little is known about effects immunomodulatory effect of GL on BC patients when used with chemotherapeutic agents. We aim to investigate the level of immune biomarkers; interferon-γ (IF-γ), tumour necrotic factor-α (TNF-α), inteleukin-8 (IL-8) and adiponectin in these patients.

Methods

Forty female patients with BC were included and divided equally to two groups, group 1 received chemotherapy alone and group 2 received chemotherapy and GL capsules (1000 mg twice daily). Blood samples were obtained from all patients before and after 4 cycles of chemotherapy. These samples were analysed to identify the levels of IF-γ, TNF-α, IL-8 and adiponectin.

Results

After the treatment period, there was significant increase of IF-γ (P = 0.0024) and significant decrease in the mean serum levels of TNF-α (P = 0.0004) and non-significant increase in IL-8 (P = 0.019) in patients treated with concurrent GL and chemotherapy. A non-significant difference was found between pre and post treatment in the mean serum levels of TNF-α, IF-γ, and IL-8 in patients received chemotherapy only. The mean serum levels of adiponectin after receiving chemotherapy only or with GL did not show any significant difference when compared to pre-treatment levels.

Conclusions

Compared to BC patients treated with chemotherapy alone, patients treated with GL and chemotherapy showed significant increase of IF-γ (a marker for immune stimulation effect) and significant decrease in the levels of TNF-α (a marker for anti-inflammation).

Legal entity responsible for the study

Hawler Medical University/College of Pharmacy

Funding

None

Disclosure

All authors have declared no conflicts of interest.

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5P - PARK2 deficiency promotes cervical tumorigenesis by deregulation in cyclin activity via P53 dependent pathway (ID 2048)

Presentation Number
5P
Presentation Topic
Basic science
Lecture Time
13:00 - 13:00
Speakers
  • Z. Hafeez
Authors
  • Z. Hafeez
  • K. Fakhri
  • Z. Iqbal
  • M. Rizvi
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

Cervical cancer is the second most common cause of cancer in women worldwide. Genetic instability in cervical cancer is commonly associated with losses or gains of function of tumor suppressor genes/oncogenes. Parkin or PARK2 gene has been considered a new candidate tumor suppressor in various types of cancer. Mutation or deletion/inactivation of PARK2 has been identified frequently in human malignant tumors. It encodes an E3 ubiquitin ligase that targets a variety of candidate substrate proteins, resulting in proteosomal degradation. This study aimed to investigate the role of PARK2 in controlling the cell cycle regulatory protein cyclin. However, the underlying molecular mechanism by which PARK2 plays a role in cancer development remains to be fully understood.

Methods

PARK2 expression level was evaluated by immunohistochemical staining of 110 cases of cervix cancer tissue microarray (TMA) slide and 10 spot were normal adjacent tissue out of 110 spot. Further, PARK2 gene was specifically knocked down in a cervical cell line by using PARK2-specific SiRNA, then cell cycle study was performed by FACS and also evaluation of the expression levels of cyclin D, cyclin E and cyclin-dependent kinases and P53 by western blot in cervical cell line in vitro.

Results

Immunohistochemical staining of cervix tissues showed mild PARK2 expression in 41% of cases. However in most cases we found loss of expression but in all normal adjacent tissue higher expression was seen. We also observed a decrease in the expression level of PARK2 cervix cancer cell lines. We examined the in vitro cell proliferation after knock down of PARK2 and found increased growth rate. Further study revealed that following knock down of PARK2, we observed a significant number of cells entering into S Phase of cell cycle and also decrease in the number of cells in G1 phase. Increase in expression levels of cyclin D and cyclin E was observed but there were no significant changes found in the level of cdk2 and cdk6. We further found a decrease in expression of P53 after blocking of PARK2 in western blot analysis.

Conclusions

These data suggest that PARK2 controls the regulation of cell cycle progression and loss of PARK2 expression links with increase in cervical cancer progression both in vitro and in vivo.

Legal entity responsible for the study

ICMR

Funding

Indian Council of Medical Research (ICMR) and UGC, India.

Disclosure

All authors have declared no conflicts of interest.

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6P - Design, synthesis and evaluation of hybrid of quinazoline–triazine derivatives as FAK inhibitor with antitumor activity (ID 1929)

Presentation Number
6P
Presentation Topic
Basic science
Lecture Time
13:00 - 13:00
Speakers
  • A. Verma
Authors
  • A. Verma
  • V. Kumar
  • P. Pathak
  • P. Shukla
  • A. Kumar
  • U. Singh
  • A. Singh
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

Focal adhesion kinase (FAK), a cytoplasmic tyrosine kinase and scaffold protein localized to focal adhesions, is uniquely positioned at the convergence point of integrin and receptor tyrosine kinase signal transduction pathways. Amplified expression of FAK is found in a variety of human cancers. Evidence supports the idea that FAK appearance in endothelial cells is necessary for the construction of new blood vessels and for the endurance of endothelial cells. Overexpression of FAK in vascular endothelial cells directly promotes angiogenesis in transgenic mice. Taking this as a prime consideration we developed hybrid of quinazoline-triazine derivatives (QTD) as a potential inhibitor of FAK for anti-cancer activity.

Methods

Designing of (QTD) was done according to molecular field mapping and alignment parameters via comparison analysis through standard angiogenic inhibitor vandetanib. Docking calculations were performed by Auto dock 4.2 for most significant comparable designed derivatives on FAK protein (PDB ID: 2ETM). QTD were synthesized through a cost-effective synthetic approach. The derivatives were evaluated for in vitro anti-cancer activity on two different cell lines, MCF-7 (Breast Carcinoma) and TPC-1 (Human Thyroid carcinoma). Further in ovo angiogenic inhibition was performed on chick embryo through CAM assay.

Results

All the designed derivatives expressed more than 50% field similarity and their atomic field conjugations. Docking studies revealed significant results compared with standard drug. The 8d showed interaction with ILE428, CYS502, and LEU501 residue of protein fragment. In terms of activity IC50 report clearly marked that selected QTD have significant proliferative inhibition against a variety of cancer cell lines, and in ovo results explored that derivatives are non-toxic to normal cells as well as significantly active against cancer induced chick embryo.

Conclusions

It has been concluded that QTD could serve as a lead for future drug discovery in cancer therapy because of significant anticancer effect via inhibition of FAK and antiangiogenic effect.

Clinical trial identification

NA

Legal entity responsible for the study

N/A

Funding

None

Disclosure

All authors have declared no conflicts of interest.

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7P - Anti-breast cancer activity of folate-chitosan nanoparticles loaded with irinotecan (ID 1936)

Presentation Number
7P
Presentation Topic
Basic science
Lecture Time
13:00 - 13:00
Speakers
  • A. Singh
Authors
  • A. Singh
  • A. Singh
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

Breast cancer is considered as the second most common cause of cancer death among women in Europe and USA, while it has a highest incident rate among women of the Asian region. Irinotecan is used as a first- and second-line regimen for metastatic colorectal, small cell lung and some other cancer types. The objective of this study was to develop Irinotecan nanoparticles (NPs) using folate‐chitosan conjugate (FCC) for more effective delivery of Irinotecan on breast cancer cells.

Methods

In this study, we synthesized the FCC system using carbodiimide synthesis. Irinotecan loaded FCC NPs were synthesized by ionic cross-linking with sodium tripolyphosphate. The effect of several variables on the NPs’ characteristics was assessed, including the amount of drug and FCC ratio. The entrapment efficiency and the particle size distribution of irinotecan were optimized by changing these variables. The cytotoxicity of the particles was evaluated by cell viability assay (MTT assay) using breast cancer cell line (MCF‐7).

Results

NPs were spherical with a comparatively mono-dispersed size distribution (average size ≈93 nm) and negative zeta potential. Selected optimized formulation (F9) showed a suitable size distribution (≈105 nm) with relatively high drug entrapment (>75%). MTT assay showed a stronger cytotoxicity of F9 against MCF-7 cancer cells than control NPs and irinotecan free drug. Since breast cancer cells express folate receptors on their surface, these irinotecan loaded folic acid–Chitosan conjugated NPs could be used for targeted delivery against metastatic breast cancer with some modifications.

Conclusions

Our study findings demonstrated that the designed NPs show suitable characteristic and also great potential for further in vivo cancer evaluation.

Clinical trial identification

Not Applicable.

Legal entity responsible for the study

N/A

Funding

None

Disclosure

All authors have declared no conflicts of interest.

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8P - Discovery of novel 1,3,5-triazine-thiozolidine (DDDL-251) based dual PI3K/mTOR inhibitor against breast cancer (ID 1982)

Presentation Number
8P
Presentation Topic
Basic science
Lecture Time
13:00 - 13:00
Speakers
  • U. Singh
Authors
  • U. Singh
  • A. Verma
  • H. Bhat
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

The targeting of phosphatidylinositol 3-kinase (PI3K) by selective inhibitors has emerged as a newer therapeutic option to reduce the burden of the cancer. The involvement of PI3K/mTOR in the progression of breast cancer is widely documented, and, as a result, numerous compounds are being assessed in clinical trials. In our previous study, we have discovered novel small molecules targeting breast cancer both in vitro and in vivo in micromolar concentration. Thus, in the present study, we intended to develop novel 1,3,5-triazine-thiozolidine based dual PI3K/mTOR inhibitor against breast cancer.

Methods

The compounds were synthesized in excellent yield and subsequently tested for anticancer activity against ER-positive (MCF-7) and ER-negative (MDA-MB-231) human breast cancer cell lines and MCF 12A (normal epithelial breast cell line) using MTT assay. The inhibitory activity against PI3K and mTOR were also estimated. The 3D-crystal structure of both PI3K and mTOR was used for the docking with DDD-251 to explore key structural contacts.

Results

The anticancer activity data revealed that compound DDDL-251 exhibits potent anticancer activity against MCF-7 and MDA-MB-231 cell lines, with the IC50 of 0.34 µM and 0.98 µM, respectively. The results of cell cycle analysis indicated that DDDL-251 causes G1/S cell cycle arrest. It was also shown to attenuate the PI3K and mTOR with IC50 of 4.05 µM and 6.55 µM, respectively. The docking analysis suggests that, DDDL-251 was able to fit into the ATP pocket of catalytic site of both PI3K amd mTOR with the Ki of 5.02 µM and 8.62 µM, respectively. Moreover, the compound was found non-toxic to the MCF 12A cells.

Conclusions

Based upon the potent anti-breast cancer activity, non-toxicity and selective targeting of both PI3K and mTOR, compound DDDL-251 could serve as a lead for future inhibitors.

Legal entity responsible for the study

Sam Higginbottom University of Agriculture, technology and Sciences.

Funding

Sam Higginbottom University of Agriculture, Technology and Sciences.

Disclosure

All authors have declared no conflicts of interest.

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9P - Anti-metastatic effect of riluzole on Mat-LyLu rat prostate cancer cell line (ID 904)

Presentation Number
9P
Presentation Topic
Basic science
Lecture Time
13:00 - 13:00
Speakers
  • S. UZUN
Authors
  • S. UZUN
  • S. Altun
  • İ. Bugan
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

Prostate cancer (PCa) is the most frequently diagnosed type of cancer among males. Deaths resulting from PCa occur due to the metastatic outcome rather than primary tumors. The increase in the expression of voltage-gated sodium channels (VGSCs) located on the cell membrane promotes the motility of cells and supports the metastatic potential. To this end, the inhibition effects of cells with metastatic characteristics on the motility of cells are examined using agents/drugs that block VGSCs. Mat-LyLu cells, a rat PCa cell line with a highly metastatic character, are known to have a high expression of VGSCs. Studies conducted with RIL, acting as a VGSC blocker, have shown that human PCa cell proliferation is inhibited. In this study, the effects of RIL on the lateral motility of rat PCa Mat-LyLu cells with the high VGSC expression will be investigated.

Methods

Mat-LyLu cells were cultured in RPMI-1640 with serum (FBS). The trypan blue method was used to assess the toxicity of RIL on Mat-LyLu cells and cell proliferation was determined by the MTT method. 'Wound healing' was applied to evaluate the lateral motility of the cells. 1, 3, and 5 μM RIL, that have no effect on cell proliferation, and tetrodotoxin (TTX), as a positive control, were used in the investigation of lateral motility. Furthermore, the control-DMSO group was added to all experiments. All experiments were repeated at least three times, and were evaluated statistically.

Results

The result of the RIL administration to Mat-LyLu cells showed that the 48h results from the control and experimental groups (1, 3 and 5 μM) did not affect the cell proliferation. However, with higher RIL concentrations, such as 10 and 20 μM, cell proliferation was significantly reduced. In the positive control group with TTX, a specific VGSC blocker, lateral motility was significantly inhibited. The lateral motility of Mat-LyLu cells in the experimental groups (1, 3 and 5 μM) decreased (P < 0.05) compared with the control groups.

Conclusions

The data obtained from the study show that RIL inhibits the lateral motility of highly metastatic rat PCa cells, Mat-LyLu, by blocking VGSCs. These first in vitro results demonstrating the potential of RIL to be used as an anti-metastatic drug suggest that the effect of RIL on the VGSCs should also be assessed in vivo.

Legal entity responsible for the study

Sercan Uzun

Funding

Istanbul University Scientific Research Projects

Disclosure

All authors have declared no conflicts of interest.

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10P - Oleic acid induced SKOV3 ovarian carcinoma cell metastasis via uPA/uPAR signaling pathway (ID 905)

Presentation Number
10P
Presentation Topic
Basic science
Lecture Time
13:00 - 13:00
Speakers
  • W. Kuan
Authors
  • W. Kuan
  • M. Tan
  • Y. Goan
  • C. Tsai
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

The highly relevant association between obesity and female cancer as well as free fatty acids (FFAs) increasing the risk of female cancer development have been shown in several epidemiological studies. Oleic acid (OA) is an abundant FFA in adipose tissue. It can promote metastatic ability of breast cancer through adjusting MMPs expression which was observed in previous studies. However, the effect of OA on the development of ovarian carcinoma still unclear.

Methods

In this study, we used an ovarian cancer cell lines, SKOV3, as a cell model to elucidate the relationship between OA and ovarian cancer. The cell viability effect of oleic acid treatment was detected by MTT assay. Metastatic ability of cancer cell was observed by Boyden chamber experiment. The highly potential target genes involved in this study were screened by microarray experiment. Antibody neutralization blocked specific receptor function and shRNA transfection were used to validate the signaling pathway of oleic acid in ovarian cancer.

Results

The result of MTT assay revealed that OA didn’t have significant influence on cell viability. However, Boyden chamber assay showed that OA can increase migration and invasion ability of SKOV3 which related to metastatic potential of cancer cell. Urokinase-type plasminogen activator receptor (uPAR) was three times higher than control group in microarray assay. In our data, uPAR expression significantly increased at 6 hours after OA treatment and the effect of overexpression can last to 48 hours in both RNA and protein levels. After blocking uPA/uPAR signaling pathway with uPAR neutralization antibody, the number of cancer cell migrating through the chamber reduced. Furthermore, cancer metastatic ability such as migration and invasion was also inhibited by knockdown uPAR expression with shRNA.

Conclusions

The result of our study demonstrated that oleic acid might involve in SKOV3 metastasis via uPAR and uPA/uPAR signaling pathway. This finding is consistent with the observation of previous studies concerning uPAR to cancer metastasis and proliferation. Accordingly, our result provides a possible linkage between obesity and ovarian cancer aggressiveness.

Legal entity responsible for the study

Tan, Main-Shin

Funding

None

Disclosure

All authors have declared no conflicts of interest.

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11P - hTERT mediated c-MET expression is p53 dependent in cancer cells (ID 1599)

Presentation Number
11P
Presentation Topic
Basic science
Lecture Time
13:00 - 13:00
Speakers
  • R. Prasad
Authors
  • R. Prasad
  • D. Mishra
  • M. Kumar
  • A. Sharma
  • P. Yadava
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

Telomerase is a ribonucleoprotein that participates in telomere maintenance. Telomerase protein component (hTERT) has been significantly involved in cancer cell survivability and proliferation. c-MET is a heterodimeric receptor protein consisting of extracellular α-subunit along with a β-subunit comprised of the extracellular, transmembrane and intracellular domains. It is activated by its ligand HGF in both paracrine and autocrine manner that triggers downstream signaling pathways; like PI3K, Gab1, STAT, and β-catenin. c-MET is overexpressed in most of cancer cells.

Methods

A549, H1299, and HCT116 cancer cells were used for investigation. RNA interference and expression vectors were used in the study. Gene expression was assayed by real-time PCR, western blotting, and immunofluorescence.

Results

hTERT down-regulation by shRNA causes a reduction in c-MET expression while hTERT overexpression increases the c-MET level in the cell. The low luciferase activity of c-MET promoter under hTERT reduced cells reflects the transcriptional regulation of the receptor protein. The c-MET promoter has known p53 binding elements, and hTERT has the negative association with p53 expression in cancer cells. To understand this crosstalk, we overexpressed p53 in A549 and H1299 cells that reflected the decreased expression of c-MET while p53 knockdown caused increased c-MET expression. Further, c-MET and hTERT knockdown have shown slow growth, proliferation and migration potential in both A549 and H1299 cells.

Conclusions

hTERT is differentially overexpressed in 90% of cancer cells. Its negative association with p53 helps in proliferation and survivability. Here, we have for the first time shown that c-MET is positively associated with hTERT expression in cancer cells. This hTERT dependant c-MET expression is mainly controlled by p53 that acts as a repressor in the c-MET promoter. Our findings suggest that the increased expression of hTERT in cancer cells downregulate p53 that triggers the c-MET expression in cells. The increased c-MET expression results in high proliferation, growth, and invasive potential in cancer cells. Although it is a preliminary finding, it suggests its role in cancer aggressiveness which makes this pathway significant in cancer therapeutics.

Legal entity responsible for the study

Prof. Pramod Kumar Yadava

Funding

Department of Science & Technology, Jawaharlal Nehru University, University Grants Commission.

Disclosure

All authors have declared no conflicts of interest.

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12P - BET inhibitors induce apoptosis through ATAD2 suppression in AR positive triple negative breast cancer cells (ID 1879)

Presentation Number
12P
Presentation Topic
Basic science
Lecture Time
13:00 - 13:00
Speakers
  • H. YANG
Authors
  • H. YANG
  • S. Shim
  • K. Lee
  • I. Park
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

Triple negative breast cancer (TNBC) is a heterogeneous disease entity with inferior outcomes to those of other subtypes. The androgen receptor (AR) is present in up to 30% of patients with TNBC.

Methods

In this study, we investigated the effect of bromodomain inhibitor (BETi), JQ1 combined with AR targeted therapy in AR positive TNBC. The activity of enzalutamide, anti-androgen drug was moderate with IC50 >10μM even in AR strong positive MDA-MB-453 TNBC cell line. JQ1 demonstrated significant anti-tumor activity in TNBC cell lines (MDA-MB-231, MDA-MB-453, MDA-MB-468, BT-20) and IC50 values were in 0.2-0.3μM range.

Results

JQ1 induced apoptosis in a dose-dependent manner, evidenced by increased levels of cleaved caspase 3, caspase 9, and PARP. Further, JQ1 treatment induced G0-G1 arrest and downregulation of cyclin E1 and cyclin A2. The treatment of JQ1 reduced cell viability synergistically when combined with enzalutamide in AR expressing TNBC cell lines. After JQ1 treatment, MYC expression had significantly reduced over 72 hrs. In addition, ATAD2, a conserved factor harboring both ATPase domain and a bromodomain, expression levels were significantly repressed with JQ1 treatment in both cell lines. Suppression of ATAD2 was more significant when JQ1 was treated in siRNA of AR treated TNBC cells.

Conclusions

Taken together, our study showed that BET inhibitor with AR targeting strategy is a promising new therapeutic option for AR positive TNBC. Further studies including in vivo analysis is planned.

Clinical trial identification

not applicable

Legal entity responsible for the study

In Hae Park

Funding

None

Disclosure

All authors have declared no conflicts of interest.

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13P - Investigate the efficacy of Photodynamic Therapy on nasopharyngeal carcinoma multicellular tumor spheroids (ID 1961)

Presentation Number
13P
Presentation Topic
Basic science
Lecture Time
13:00 - 13:00
Speakers
  • R. Wu
Authors
  • R. Wu
  • E. Chu
  • J. Yuen
  • Z. Huang
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

Nasopharyngeal Carcinoma (NPC) is one of the top ten cancers with the annual incidence of over 800 new cases in Hong Kong. Chemo-radiotherapy is the conventional treatment for NPC yet failure of therapies is found to be associated with the advanced staging, distant recurrence and multi-drug resistance properties. Photodynamic Therapy (PDT) is one of the alternative therapeutic approaches proved to be effective on NPC. In this study, multicellular tumor spheroid models established were used to evaluate the effect of PDT.

Methods

To evaluate the effect of a photosensitizer, FosPeg®, multicellular tumor spheroids were generated with multi-cellular layer (MCL) and multi-cellular spheroid (MCS) models using NPC/C666-1 cells. 1 x 105 cells were cultured in 96 well plate for 2D, 3D MCL (agarose basement) and MCS (hanging drop) models. PDT efficacy were revealed via phototoxicity assay (MTT assay) and photobleaching analysis. Photobleaching effect after laser activation was evaluated using fluorescence microscopy and ImageJ software. The photobleaching effect was evaluated and presented as the percentage of photobleaching.

Results

Multicellular tumor spheroids were obtained in day 3 in both models. The drug was incubated for 24 hours in both 2D and 3D spheroids models. FosPeg® PDT was effective in all NPC cell culture models with no dark toxicity identified. As expected, FosPeg® PDT was more effective on 2D model than 3D models. LD25 and LD50 were obtained at 0.001 μg/mL and 0.0025 μg/mL of FosPeg® in 2D model and at 0.1 μg/mL and 1 μg/mL of FosPeg® in both MCL and MCS models. This finding was echoed with the photobleaching analysis that FosPeg® was photobleached after laser activation in a time dependent manner, with 19.9%, 18.1% and 17.8% of photobleaching obtained at 10 minutes post PDT in 2D, MCL and MCS models respectively.

Conclusions

FosPeg® PDT was more effective in 2D model than 3D multicellular tumor spheroids models. Further investigation is needed on PDT mediated cellular changes using multicellular tumor spheroids models.

Acknowledgement: The work described here was fully supported by a grant from the Research Grants Council of the Hong Kong Special Administrative Region, China (project no.: 2015-00-74-RGC150201).

Clinical trial identification

NIL

Legal entity responsible for the study

None

Funding

Research Grants Council of Hong Kong Special Administrative Region

Disclosure

All authors have declared no conflicts of interest.

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14P - Evaluating anti-oxidant potential of Callistemon viminalis leaves extracts and their compounds in STAT 3 pathway in liver cancer (ID 918)

Presentation Number
14P
Presentation Topic
Basic science
Lecture Time
13:00 - 13:00
Speakers
  • K. Ahmad
Authors
  • K. Ahmad
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

Aim of this study was to identify antioxidant and anticancer compounds present in the C. viminalis leaves extracts and its anticancer activity against liver cancer cell lines by inhibiting STAT3 protein.

Methods

The free radical scavenging potential of various extract of C. viminalis leaves were determined by the DPPH, superoxide anion radical scavenging, hydrogen peroxide scavenging, nitric oxide scavenging and reducing power assay. The anticancer activity of C. viminalis leaves extracts have been evaluated against human embryonic kidney (HEK-293) cell line, human liver cancer (HepG-2) and breast cancer (MCF-7) cell lines. The chemical composition of C. viminalis is analyzed by gas chromatography/mass spectrometry (GC-MS).

Results

The results were revealed that ELE and MLE extracts of C. viminalis are better sources of antioxidants. ELE and MLE extracts reduced HepG-2 cell growth and ROS generation. Interestingly, our result indicates that reduction in potential of cell migration enhances anti-metastasis activity of ELE and MLE and induction of apoptosis and cell cycle arrest in G0/G1 and S phase, suggesting the ELE and MLE extracts induced apoptosis and reduce the cell proliferation. ELE and MLE reduced the STAT3 mRNA expression and increased the p53 mRNA expression, as confirmed by RTPCR and also reduced the STAT3 protein expression and increased the p53 protein expression, as confirmed by western blot. The anticancer activity of ELE and MLE extracts against liver cancer cell lines by inhibiting of STAT3 protein are possibly due to presence of active anticancer compounds identified by GC/MS. Molecular docking results revealed that the hydrophobic and hydrogen bond interactions are the main force for binding of compounds of extracts ELE and MLE with the STAT3.

Conclusions

The ELE and MLE extracts reduces the cell proliferation against liver cancer cell lines by inhibiting of STAT3 protein and can be successfully exploited in the herbal formulation of cancer chemoprevention and chemotherapy.

Legal entity responsible for the study

Jamia Millia Islamia

Funding

None

Disclosure

All authors have declared no conflicts of interest.

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15P - The n-hexane fraction of Myrmecodia pendans suppresses survival and proliferation in colon cancer cells (ID 1392)

Presentation Number
15P
Presentation Topic
Basic science
Lecture Time
13:00 - 13:00
Speakers
  • Y. Ruswandi
Authors
  • Y. Ruswandi
  • S. Hidayat
  • F. Huda
  • T. Putri
  • N. Qomarilla
  • D. Kurnia
  • M. Satari
  • M. Bashari
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

Colon cancer is a major cause of morbidity and mortality in the world. Some patients develop resistance to chemotherapeutic agents, therefore discovering a novel anti-cancer agent is urgently needed. Myrmecodia pendans, sarang semut (local name), is one of Indonesia’s potential natural resources for cancer therapy that has been studied in some cancer entities. The aims of this study were to determine anti-tumor activities of sarang semut in colon cancer cell lines.

Methods

Anti-tumor activities of sarang semut were evaluated in Caco-2 and HCT-116 cells using MTT assay for cell death and inhibitory concentration (IC50), clonogenic assay for plating efficiency (%), and colony area per cell seeded (mm2) as well as serial trypan blue exclusion assay for doubling time and cell growth curve. Data were considered significantly different if p < 0.05.

Results

Survival of Caco-2 cells was prominently decreased by the n-hexane fraction of sarang semut than the methanol extract or ethyl acetate fraction. The IC50 of the n-hexane fraction was 24 ppm and 30 ppm in Caco-2 and HCT-116 cells, respectively. Moreover, the n-hexane fraction of sarang semut inhibited colony formation in Caco-2 cells, shown by the difference of plating efficiency (p < 0.05) and colony area per seed (p < 0.001) of control group compared with the treatment group. In addition, the n-hexane fraction of sarang semut triggered prolongation of doubling time of Caco-2 cells.

Conclusions

The n-hexane fraction of sarang semut demonstrates potent antitumor activity in colon cancer cells; in particular it inhibits cell survival and proliferation.

Legal entity responsible for the study

Muhammad Hasan Bashari

Funding

Fundamental Research Grant from Universitas Padjadjaran for MHB (no.855/UN6.3.1/PL/2017).

Disclosure

All authors have declared no conflicts of interest.

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16P - Is there a link between BRCA1 and BRCA2 mutations and obesity, high blood pressure and diabetes mellitus in Romanian high-risk breast cancer cases? (ID 1719)

Presentation Number
16P
Presentation Topic
Basic science
Lecture Time
13:00 - 13:00
Speakers
  • N. Antone
Authors
  • N. Antone
  • L. Pop
  • E. Dronca
  • A. Stoian
  • R. Matei
  • M. Ligtenberg
  • H. Ouchene
  • A. Onisim
  • O. Rotaru
  • R. Eniu
  • A. Eniu
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

A systematic analysis to determine the frequency of obesity, high blood pressure (HBP) and diabetes mellitus (DM) for high-risk breast cancer(BC) patients (pts) BRCA1/2 (B1, B2) mutated vs pts without B1/B2 mutations.

Methods

This prospective study evaluated 44 pts with B1/B2 pathogenic mutations vs 191 non-mutated high-risk BC pts, tested in IOCN during 2015-2016. Inclusion criteria: triple negative BC < 50, or having conventional family history criteria. HBP and DM data were ascertained by self-reported personal history. Obesity was determined by calculating BMI at first breast cancer diagnosis. All pts signed the informed consent. B1/B2 testing was performed using an AmpliSeq-based sequencing analysis, on the Ion Torrent Personal Genome Machine at RCFG. Pathogenic mutations were validated using Sanger technology. MLPA was performed for all pts.

Results

Out of 44 BC pts, 29 (11.6%) pts B1 mutated, 15 (6%) pts B2 and 191 pts had no B1/B2 deleterious mutations. The median age at diagnosis was 39 yo (28-74) in the B1/B2 mutated group and 37 yo (23- 80) for pts without B1/B2 mutations, p = 0.1122. In B1/B2 mutated pts, 22(50%) had normal weight, 13(29.54%) were overweight and 9 (20.45%) were obese. In the non-mutated group 4 (2.11%) pts were underweight, 114 (60.31%) had normal weight, 49(25.92%) pts were overweight and 22(11.64) were obese, p = 0.0742. Regarding HBP, in the B1/B2 mutated, 9 (20.45%) pts presented the condition in their personal history, while 35(79.54%) had no history of HBP, and in the non-mutated group, 15 (7.98%) pts related history of HBP and 173 (92.02%) pts did not have HBP, p = 0.0246, statistically significant when comparing the subgroups. In the B1/B2 mutated group, only 1 (2,27) patient related DM as comorbidities, while 43(97.23%) pts did not present the disease vs 5(2. 80%) pts with DM and 174 (97.20%) pts who did not have DM in the non- mutated group, p = 0.9999.

Conclusions

This prospective study represents the first analysis of conditions such as obesity, HBP and DM in Romanian high-risk BC pts. Our results indicate that HBP is a more frequent comorbidity in Romanian high risk BC B1/B2 mutated pts when compared with pts without B1/B2 deleterious mutations.

Clinical trial identification

NCT02317120.

Legal entity responsible for the study

Alexandru Eniu

Funding

International Innovation Grant-Conquer Cancer Foundation

Disclosure

All authors have declared no conflicts of interest.

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17P - Endocrine disrupting chemicals, bisphenol A alters cardiomyocytes beating rate and cell morphology (ID 1835)

Presentation Number
17P
Presentation Topic
Basic science
Lecture Time
13:00 - 13:00
Speakers
  • S. Sheikh Abdul Kadir
Authors
  • S. Sheikh Abdul Kadir
  • Z. Rasidi
  • N. Hanafi
  • R. Kamaludin
  • S. Ab. Rahim
  • R. Siran
  • M. Othman
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

Endocrine disrupting chemicals such as Bisphenol A (BPA) has the potential to cause adverse effects to health by disrupting normal human homeostasis. BPA is widely used plasticizer and it is an ideal polymer for epoxy resins and polycarbonates. Therefore, humans are regularly exposed to this chemical through ingestion of water, food and beverages which are contaminated with BPA. Studies have linked BPA exposure in humans with the risk of cardiovascular disease development, yet the direct effects of BPA on cardiomyocytes morphology have not been entirely explored. In here we aimed to investigate the cytotoxic effects of BPA on cells structure of isolated neonatal rat cardiomyocytes culture.

Methods

Cardiomyocytes were isolated from newborn Sprague Dawley rats. Cardiomyocytes were treated with 10-7 to 10-4 M of BPA and subjected for beating rates experiment, cell viability assay and Scanning Electron microscopy. In beating rate experiment, significant reduction in rates (50% -55%, ± 1.5275, p ≤ 0.05) were observed in cardiomyocytes treated with 10-7 to 10-4 M of BPA.

Results

In beating rate experiment, significant reduction in rates (50% -55%, ± 1.5275, p ≤ 0.05) were observed in cardiomyocytes treated with 10−7 to 10−4 M of BPA. Interestingly, cell viability was markedly reduced (54%, ± 0.0026, p ≤ 0.05) in cardiomyocytes treated with 10−7 M of BPA compared to cells in untreated group and others BPA concentration. Cardiomyocytes show altered cell surface homogeneity after BPA exposure. The signs of flattening cardiomyocytes cell surface, reduction of the size, and blurring of the cell borders were observed and evident after exposure to 10−7 to 10−4 M of BPA.

Conclusions

This study provides in vitro evidence of the potential adverse effects of BPA on cardiomyocytes morphology. However, further investigation would be required to understand how BPA is likely to be potentially hazardous to heart and other heart cells.

Legal entity responsible for the study

Universiti Teknologi MARA Animals Ethics Committee

Funding

None

Disclosure

All authors have declared no conflicts of interest.

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18P - Surface engineered nanocapsules of crocetin as a novel inhibitor of VEGFR2 on cancer induced chick embryo (ID 1925)

Presentation Number
18P
Presentation Topic
Basic science
Lecture Time
13:00 - 13:00
Speakers
  • V. Kumar
Authors
  • V. Kumar
  • M. Rahman
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

Angiogenesis plays a fundamental and decisive role in the development of solid tumor growth and progression of chronic inflammation. Malignancies constantly generate certain mediators which are inducing proliferation, expression, angiogenesis and permitting tumor cells. Judah Folkman and colleagues suggested the concept of angiogenic inhibition of tumor growth. Vascular endothelial growth factor (VEGF) is a multifunctional protein, expressed and secreted during wound healing and tumor angiogenesis via pro-angiogenic factors. VGEF is a prime target for scrutinizing therapeutic agents because it is a validated significant pathway. Considering this we have fabricated the surface engineered nanocapsules of crocetin as a potential VEGFR2 kinase inhibitor for anticancer effect.

Methods

Emulsion solvent evaporation technique was used for the preparation of crocetin-loaded PLGA nanoparticles (CA-PLGA-NP) and poly-disparity, particle size, drug release potency and zeta potential were scrutinized, respectively. Further docking study was performed via using the docking server for scrutinized the cost effective drug. Flow cytometirc, MTT assay and confocal microscope analyses were performed on human hepatocellular carcinoma cell lines HepG2 and HuH-7, and further chick embryo was used for determination of in ovo angiogenic inhibition. The formulation was further labeled with technetium-99m to scrutinize the biodistribution, and scintigraphic study following intravenous administration in solid tumor bearing mice was also performed.

Results

The prepared formulation of crocetin showed the smooth spherical small surface with relative narrow size distribution. In cell lines study, the formulation demonstrated higher cyto-toxicity compared with the free drug due to enhanced cellular uptake (in vitro). CA showed the potent protein inhibitor of VEGFR2 in docking study. IC50 value clearly showed that CA-PLGA-NP has significant anti-proliferative effect against HCC cell lines, and in ovo study clearly suggested that CA-PLGA-NP is nontoxic to normal cells. The scintigraphic image and radiolabeled CA-PLGA-NP showed slower blood clearance and higher uptake of formulation into the tumor site.

Conclusions

Collectively, we can conclude that we have developed a novel formulation for hepatic cancer.

Clinical trial identification

None

Legal entity responsible for the study

Sam Higginbottom University of Agriculture, Technology & Sciences (SHUATS)

Funding

None

Disclosure

All authors have declared no conflicts of interest.

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19P - Effectiveness of Liposomal Doxorubicin on MDR-1-Related Drug Resistance in Dedifferentiated Chondrosarcoma In vitro 2D and 3D Culture (ID 1096)

Presentation Number
19P
Presentation Topic
Basic science
Lecture Time
13:00 - 13:00
Speakers
  • E. Cakiroglu
Authors
  • E. Cakiroglu
  • T. Uysal
  • Y. Baskin
  • H. Ellidokuz
  • I. Oztop
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00
Basic science Poster lunch Poster Display session

20P - Discovery of novel 2beta-hydroxybetulinic acid 3beta-oliate via NF-κB pathway in diethylnitrosamine induced hepatocellular carcinoma in rats (ID 1912)

Presentation Number
20P
Presentation Topic
Basic science
Lecture Time
13:00 - 13:00
Speakers
  • D. Ahmed
Authors
  • D. Ahmed
  • M. Sharma
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

Hepatocellular carcinoma (HCC) is the one of the major health problem in the world, is a leading cause of cancer related mortality. NF-kB pathways is considered as the singling pathway which activates the various cellular function including cell expansion, survival, proliferation and vesicular transport and found frequently dysregulated pathway in HCC. Consequently, natural product based inhibitors play a significant role in the NF-kB pathway and extensively scrutinized in the targeting the cancer in recent years. Present study was aimed to scrutinize the effect of 2beta-hydroxybetulinic acid 3beta-oliate (HBO) as NF-kB inhibitors for hepatic cancer.

Methods

Swiss albino Wistar rats (48) were divided into four groups. Diethylnitrosamine (DEN) (200 mg/kg) dose was used for induction the HCC in rats and treated with the HBO for 22 weeks. Pro-inflammatory cytokines including IL-6, TNF-α, IL-1β and NF-κB expression were estimated, respectively. Docking analysis was also performed with NF-kB (PDB:1NFK) to explicate imperative structural residues essential for bioactivity.

Results

HBO significantly (p < 0.001) altered the hepatic parameters such as AFP, AST, ALT along with the biochemical and antioxidant parameters. DEN group rats suggest the expansion of hepatic nodules, which was reduced by HBO dose dependently. DEN up-regulated the proinflammatory cytokines including IL-6, TNF-α, IL-1β and NF-κB, which suggest the expansion of hepatic inflammation during cancer and down-regulated by HBO. Whereas, docking research results exhibits that compound HBO was found to be efficient to inhibit NF-kB by binding the ATP pocket through interaction with SER888, GLY705, PRO853, TRP707 and GLY893.

Conclusions

Collectively, we may conclude that HBO has shown excellent activity towards down-regulation of HCC via inhibition of NF-kB pathways supported by molecular docking research analysis. Therefore, HBO could be a potential candidate for hepatic cellular carcinoma.

Legal entity responsible for the study

SHUATS

Funding

SHUATS

Disclosure

All authors have declared no conflicts of interest.

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21P - Liposomal nanoparticles for photomagnetic controlled drug release with radical pair mechanism (ID 2114)

Presentation Number
21P
Presentation Topic
Basic science
Lecture Time
13:00 - 13:00
Speakers
  • H. Nakagawa
Authors
  • H. Nakagawa
  • M. Ohuchi
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

It is generally well known that the use of magnetic fields has an undoubtedly long-range potential when aided with high substance permeability, although their essential forces must be of low energies. That’s why numerous techniques have been developed to investigate magnetic nanoparticles for biomedical engineering applications to drug-delivery systems (DDSs). On the other hand, judging from the best of our knowledge, there are almost no reported studies of the application of radical pair mechanisms (RPMs) to drug-release controlling under exposure to magnetic fields.

Methods

The triplet yield ΦTT affected by magnetic field effects (MFEs), which is equivalent to escape-radical yields with the effects, can be calculated based on RPM as follows: ØT = kT|CT|2/kT|CT|2 + kS(1–|CT|2) where kTT is the release-rate constant of free radicals derived from a triplet radical pair, kSS is the formation-rate constant of a cage product derived from a singlet radical pair, and |CTT|2 is the existence probability of the triplet radical pair. Moreover, in the definite case of kTT=kSS=k, the yield ΦTT as a function of the field strength can be approximated as follows: ØT = k∫0|CT|2e–ktdt The preparation of flutamide (FM)-containing liposomes and the field-effect measurements with FM release were carried out in the same way as in our previous reports.

Results

When the magnetic field strength was set up in the range of 0.1–0.2 T, competition between MFEs and the FM-related escape-radical release was observed depending on the field strength. In contrast, MFEs with a field of 40 mT were not extensive under our experimental conditions. Concerning three kinds of liposomes prepared in this study, the field effects obtained using a homogenous field of 0.2 T were more extensive on the order of 67%–75%, than those obtained at a geomagnetic field.

Conclusions

In this study, we considered applying the RPM to DDS methodologies for the best possible balance between clinical performance and low invasivity. Our liposomal drug-release technology with magnetic controls must be one of the most adaptable DDS.

Legal entity responsible for the study

N/A

Funding

Japan Society for the Promotion of Science (JSPS)

Disclosure

All authors have declared no conflicts of interest.

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22P - Non-coding MIR491 is associated with less EGFr expression and greater radiosensitivity in human head and neck cancer cell lines (ID 2133)

Presentation Number
22P
Presentation Topic
Basic science
Lecture Time
13:00 - 13:00
Speakers
  • J. Bonner
Authors
  • J. Bonner
  • E. Yang
  • H. Trummell
  • S. Nozell
  • C. Willey
  • M. Bredel
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

Non-coding RNAs, such as microRNAs (miRs), are often affected by loss or amplification of adjacent tumor suppressor genes or oncogenes, respectively. MIR491 is located in close proximity to the CDKN2A locus and is frequently co-deleted with CDKN2A. MIR491 expression has correlated with inhibition of EGFr. Also, knockdown of MIR491 has been shown to increase cellular proliferation and invasion in glioma cells [Li, X et al. Oncogene, 34(13):1619-1628, 2015]. Since MIR491 deletion has been demonstrated in head and neck cancer, we sought to assess the effect of increasing MIR491 expression on EGFr expression as well as downstream signaling events and radiosensitivity.

Methods

Four human head and neck squamous cell carcinoma cells lines were studied (UM-SCC-1, UM-SCC-1R, UM-SCC-6 and UM-SCC-6R). The UM-SCC-1R and UM-SCC-6R cells were developed as cetuximab resistant cells after several months of continuous exposure to cetuximab. Previously published methods were used to transfect cells with MIR491. Also, previously described methods were used for assessments of EGFr and other downstream proteins (by immunoblot), cell proliferation, colony formation and apoptosis (annexin assay). [Bonner JA. Radiother Oncol, 92:338-344, 2009].

Results

MIR491 transfected human head and neck squamous cell carcinoma cells (UM-SCC-1, UM-SCC-1R, UM-SCC-6 and UM-SCC-6R) showed decreased expression of phosphorylated EGFr and phosphorylated AKT by immunoblot. Furthermore, these decreases in EGFr and EGFr-signaling proteins correlated with enhanced radiosensitivity as assessed by cell proliferation and colony formation. This enhanced radiosensitivity correlated with greater radiation-induced apoptosis.

Conclusions

These results suggest that MIR491 is a negative regulator of EGFr in head and neck cancer and that deletions of the non-coding MIR491 gene may be associated with radiation resistance, and may contribute to poor outcomes for certain tumors that are treated with radiotherapy. Further work will be necessary to determine if MIR491 deletions are associated with greater tumor recurrence following radiation or other DNA-damaging cancer treatments.

Clinical trial identification

N/A

Legal entity responsible for the study

James Bonner

Funding

University of Alabama Health Services Foundation

Disclosure

J.A. Bonner: Occasional consultant/honoraria for Bristol-Myers Squibb Company, Eli Lilly and Company, Merck Serono, and Cel-Sci. E.S. Yang: Advisory Board SRATA Oncology, Research Support Eli Lilly, Novartis Research Support-AACR, Bayer C. Willey: North, Pursell & Ramos, PLC - medical-legal consultations for malpractice case review.

All other authors have declared no conflicts of interest.

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25P - Utility of neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and mean platelet volume (MPV) predictive and prognostic biomarkers in patients with hepatocellular carcinoma, prostate carcinoma, stomach carcinoma, aplastic anemia (ID 2092)

Presentation Number
25P
Presentation Topic
Biomarkers
Lecture Time
13:00 - 13:00
Speakers
  • V. Srikanth
Authors
  • V. Srikanth
  • M. Pillai
  • T. Tushar
  • J. Ashwin
  • K. Cinzia
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

Malignancies like hepatocelluar carcinoma, carcinoma stomach, aplastic anemia, prostate cancer which can be easily missed if not strongly suspected, these group of population generally reach the hospital at the later stage of the diseases where their treatment option becomes limited. In this study, we have evaluated the predictive and prognostic utility of NLR, PLR and MPV for earlier predicting as a biomarker.

Methods

We have conducted this study by screening all the patients who got admitted between January 2013 and June 2017. The data collected were analyzed for neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, mean platelet of 100 cases in each group of hepatocellular carcinoma, carcinoma stomach, aplastic anemia, prostate cancer. Control group of with no known comorbidities were taken to find the normal cut off value of NLR, PLR and MPV and was validated with other similar studies. Inclusion criteria were all the patients with admitted with a diagnosis of hepatocellular carcinoma, carcinoma stomach, aplastic anemia, prostate cancer. Exclusion criteria: all cases other than the test group. Patients with other associated malignancies and inflammatory state.

Results

Male preponderance was seen in all the malignancies. The incidence of hepatocellular carcinoma was more in the low socio-economic group where other malignancies were equally prevalent in all the socio-economic groups. NLR and PLR were highly significant with a p – value 0.001 and p – 0.001 to be used as a biomarker in predicting the malignant conditions. MPV was statistically insignificant to use a prognostic biomarker.

Conclusions

From our study, we conclude that NLR, PLR are better and cost-effective predictor and prognostic biomarker in malignant condition. These ratios of NLR and PLR can be interpreted from a peripheral smear at the primary health care level in rural part of the developing country like India. This simple and cost-effective test will reduce the financial burden and better patient care in early identification and monitoring the prognosis of diseases.

Legal entity responsible for the study

Dr. V.S. Srikanth

Funding

None

Disclosure

All authors have declared no conflicts of interest.

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26P - Essential roles of microRNA-222 containing exosomes in breast cancer with chemotherapeutic resistance (ID 1416)

Presentation Number
26P
Presentation Topic
Biomarkers
Lecture Time
13:00 - 13:00
Speakers
  • S. Yang
Authors
  • J. Tang
  • S. Yang
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

To date, although many significant advances have been made in chemotherapy, chemo-resistance still remains a major obstacle to successful treatment of breast cancer. For poor understanding of the mechanisms underlying chemo-resistance, it is necessary to identify the possible biomarkers and pathways in breast cancer resistant to chemotherapy. On the basis of our previous finding that drug-sensitive breast cancer cells could partly increased their resistance capacity by the uptake of drug-resistant cell-derived exosomes, which contain some higher levels of miRNAs (miR-100, miR-222, and miR-30a).

Methods

To identify the mechanism of exosome-mediated drugresistance, we compared the characteristics of exosomes derived from MCF/7-ADR and MCF/7-S cell lines.

Results

A marked increase in the exosome release was observed in ADR-resistant cells compared with sensitive cells. Then, we confirmed that exosomes from MCF/7-ADR cells confer drug-resistance to sensitive cells, with the modulation of the miR-222 level. To exclude effects of other relevant factors on resistance, we chose exosomes produced by HBL-100 cells as a suitable carrier for loading miR-222 mimic (or inhibitor), which was achieved by electroporation. The electroporation conditions were optimized in terms of the voltage and exosome concentration. Importantly, we further examined the influence of miR-222 inhibitor-containing exosomes (inhibitor-exos) on the pathways downstream of miR-222 and the potential therapeutic effects both in vitro and in vivo. Mice bearing MCF-7/ADR xenograft tumors that were injected with inhibitor-exos showed greatly suppressedtumor growth, along with a lower miR-222 level and higher PTEN expression. Similar results for the miR-222 and PTEN levels were observed in serum exosomes from the mice injected with inhibitor-exos compared with the control mice. More importantly, for the first time, we detected the levels of miR-222 and its target gene, PTEN, along with the exosomal marker TSG101, in breast cancer patients who received anthracycline/taxane-based chemotherapy to explore the potential clinical implications of miR-222-containing exosomes in chemotherapy.

Conclusions

These findings demonstrate that miR-222-containing exosomes transmit drugresistance by modulating the miR-222 pathway; furthermore, miR-222-containing exosomes may be a promising biomarker for predicting the efficiency and outcome of chemotherapy in breast cancer patients.

Legal entity responsible for the study

Nanjing Medical University

Funding

None

Disclosure

All authors have declared no conflicts of interest.

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27P - High-throughput proteome identifies ANHAK as a novel biomarker for bladder urothelial carcinoma diagnosis in liquid-based cytology (ID 1520)

Presentation Number
27P
Presentation Topic
Biomarkers
Lecture Time
13:00 - 13:00
Speakers
  • H. Lee
Authors
  • H. Lee
  • H. Ryu
  • D. Han
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

Urine cytologic examination is the most widely used noninvasive pathologic test to screen bladder urothelial carcinoma (BLCA). However, inadequate diagnostic accuracy remains the major challenge to be solved. We performed high-throughput proteomcis in ten paired samples of BLCA and benign urothelial lesion (BUL) to identify ancillary proteomic markers in liquid-based cytology (LBC).

Methods

All samples were analyzed by in-depth quantitative protomics mass spectrometry (MS) to indicate differentially expressed proteins (DEP) between two groups. MS data were analyzed using a combination of MaxQuant and Perseus computational platforms, and a total of 4,839 proteins were identified, and 112 DEP were confirmed to be significantly altered proteins in BLCA group compared with BUL group (FDR q value <0.05). Independent MS-based proteomic data using tissue samples and comparative mRNA expression profiles in TCGA were analyzed for biomarker discovery using the matching method.

Results

As a consequence, 12 proteins including ACACA, AHNAK, ATP1A1, DSG1, EIF4A1, EPPK1, HSP90AB1, MYH14, RPS8, TOP2B, TUBB and YWHAZ were identified as putative candidates to apply to immunostaining. To determine immunocytochemical expression in LBC, protein expression was screened according to The Human Protein Atlas and six proteins finally enrolled to validate immunoreactivity in independent LBC cohorts where AHNAK was confirmed a unique intracellular protein translocation in immunostaining depending on tumor or non-tumor cells.

Conclusions

This finding provided a new biomarker which can be applicable to discriminate between BLCA and BUL in LBC. To our knowledge, the present study provides the first evidence of the identification of a clinical biomarker from LBC based on in-depth proteomics.

Legal entity responsible for the study

N/A

Funding

None

Disclosure

All authors have declared no conflicts of interest.

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28P - Next generation proteomic profiling to predict the response to neoadjuvant chemotherapy in breast cancer (ID 1598)

Presentation Number
28P
Presentation Topic
Biomarkers
Lecture Time
13:00 - 13:00
Speakers
  • H. Ryu
Authors
  • H. Ryu
  • D. Han
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

Since GEPARDUO trial reported the therapeutic benefit of combined doxorubicin and cyclophosphamide regimen in sequential administration with docetaxel, the combination regimen has become a standard therapeutic strategy in neoadjuvant systemic therapy for patients with operable breast cancers. However, pathologic complete response (pCR) rate is still low, ranging from 28% to 47%. Therefore, the need for a marker predictive of response to a particular cytotoxic regimen, especially before neoadjuvant chemotherapy, is becoming all the more necessary to optimize therapeutic efficacy and to avoid unnecessary complications caused by systemic therapy. Various predictive models and parameters for chemotherapeutic response have been reported thus far, especially based on transcriptional gene signatures; however, there remain difficulties employing them in routine practice due to lack of consistency and reproducibility caused by tumor heterogeneity, in breast cancer. The rapid advances of proteomic technologies with computational algorithms and biochemical technologies have recently enabled quantitative analyses to evaluate novel diagnostic markers’ discovery in practical quantities of tumor tissues.

Methods

We performed high-throughput proteomics in twenty paired core needle biopsy samples with operable breast cancer who received preoperative NAC followed by surgical resection. All samples were analyzed by in-depth quantitative protomics mass spectrometry (MS) to indicate differentially expressed proteins (DEP) between two groups.

Results

MS data were analyzed using a combination of MaxQuant and Perseus computational platform, and a total of 6,900 proteins were identified identified and 254 DEP were confirmed to be significantly altered proteins related to chemotherapeutic response.

Conclusions

To our knowledge, the present study provides the first evidence to identify a predictive biomarker for chemotherapeutic response based on in-depth proteomics.

Legal entity responsible for the study

N/A

Funding

None

Disclosure

All authors have declared no conflicts of interest.

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29P - Clinical significance of the wild-type p53-induced phosphatase 1(Wip1) expression in invasive breast cancer (ID 855)

Presentation Number
29P
Presentation Topic
Biomarkers
Lecture Time
13:00 - 13:00
Speakers
  • Y. Inoue
Authors
  • Y. Inoue
  • N. Yamashita
  • E. Tokunaga
  • H. Saeki
  • E. Oki
  • H. Kitao
  • Y. Maehara
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

Wild-type p53 inducible phosphatase 1 (Wip1), encoded by the protein phosphatase magnesium dependent 1 delta (PPM1D), inhibits p53. PPM1D amplification has been reported in breast cancer. Breast cancer can be partly developed without TP53 mutation. In such cases, the p53 pathway may be disrupted by alternative mechanisms, and Wip1 is reported to be one of the key molecules.

Methods

Primary invasive ductal carcinoma specimens were obtained from 201 patients. We evaluated Wip1 mRNA expression, Wip1 and p21 protein expression, PPM1D DNA copy number and their relationships with the clinicopathological factors and the prognosis.

Results

Nuclear expression of Wip1 protein was positive in 21 cases (10.4%). PPM1D DNA copy number was significantly correlated with Wip1 protein expression. All cases with PPM1D amplification by single-nucleotide polymorphism-comparative genomic hybridization array showed positive nuclear Wip1 expression. Wip1 protein expression was positively correlated with p21 expression. Wip1 protein expression was significantly associated with poor recurrence-free survival (RFS) (p = 0.0274). However, there was no significant correlation between Wip1 protein expression and overall survival (OS). There was no significant correlation between p21 expression and prognosis. In terms of the combination analysis of Wip1 and p21 expression, Wip1 positive and p21 negative cases showed the significantly shorter PFS and relatively shorter OS compared to the other groups.

Conclusions

Wip1 protein expression may be regulated by PPM1D amplification, independent of TP53 status. Positive Wip1 and negative p21 expression showed the poorest prognosis and suggests the loss of p53 function.

Legal entity responsible for the study

Kyushu University

Funding

None

Disclosure

All authors have declared no conflicts of interest.

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30P - A liquid biopsy gene panel for pancreatic cancer detection (ID 1220)

Presentation Number
30P
Presentation Topic
Biomarkers
Lecture Time
13:00 - 13:00
Speakers
  • K. Kato
Authors
  • K. Kato
  • K. Ohkawa
  • R. Takada
  • H. Uehara
  • Y. Kukita
  • K. Katayama
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

Since surgical resection of localized pancreatic cancer improves overall survival, its early detection would have substantial benefits. Circulating tumor DNA, which is drawing attention as a part of liquid biopsy, might be useful for pancreatic cancer detection. Although KRAS mutations appear in the majority of pancreatic cancer cases, screening for other gene mutations in plasma may improve detection.

Methods

We used the non-overlapping integrated read sequencing system (NOIR-SS), a next-generation sequencing method with improved accuracy, to sequence a panel of pancreatic cancer-related genes including KRAS, TP53, SMAD4, CTNNB1, CDKN2A, GNAS, HRAS, and NRAS (comprising 2.8 kb of genomic DNA) in plasma DNA. NOIR-SS eliminates PCR/sequencing errors by building a consensus sequence from reads with the same molecular barcode.

Results

Of 77 patients with localized pancreatic cancer, 9 (11.7%) and 16 (20.8%) patients were variant-positive for KRAS and any of the aforementioned genes. Of 67 patients with metastatic pancreatic cancer, 28 (52.2%) and 35 (41.8%) patients were variant-positive for KRAS and any of the aforementioned genes. No variant was detected in 12 healthy individuals. Of 20 patients with intra-ductal papillary mucous neoplasms (IPMN), only one mutation in TP53 was found.

Conclusions

The sequencing system removed artifacts during the assay process, and achieved near complete elimination of variant detection in control populations, namely in healthy individuals and IPMN. Sequencing of pancreatic cancer-related genes revealed an approximately 10% increase in detection rate from that with KRAS alone, thus demonstrating the merit of analyzing multiple genes.

Legal entity responsible for the study

Osaka International Cancer Institute

Funding

None

Disclosure

K. Kato: Employment (part time): DNA Chip Research Inc. All other authors have declared no conflicts of interest.

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31P - Cell-free circulating tumor DNA (CFTDNA) – in cervical carcinoma: A diagnostic and screening marker (ID 1361)

Presentation Number
31P
Presentation Topic
Biomarkers
Lecture Time
13:00 - 13:00
Speakers
  • H. Govardhan
Authors
  • H. Govardhan
  • I. Khaleel
  • N. Sarkar
  • S. Supriya
  • M. Suma
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

There are many diagnostic modalities are developed or under development to improve the diagnostic ability and to prognosticate in patients with cervical carcinoma. Cell-free circulating tumor DNA (CFTDNA) is one among them. In this study we are aiming to know the diagnostic ability at diagnosis of CFTDNA and to create genetic screening tool to detect cervical carcioma.

Methods

A total of 25 patients with locally advanced squamous cell carcinoma of cervical cancer (stage IIA-IIIB) were tested prospectively with a 50-gene tumor panel in a NABL accredited laboratory. 4 ml serum was collected, CfTDNA was isolated and they were checked for single nucleotide variants (SNVs) genes/copy number variants (CNVs) by using NGS and tumor FFPE blocks were again rechecked by NGS or PCR for the same genetic alterations.

Results

Average patient age was 50.5 (range 35-83). In 23/25 (88.8%) patients, CfTDNA was detected and sufficient to carry under NGS. Out of 50 genes, around 31 genetic alterations were detected. Mean genetic alteration was 4.7 (2-15). In 4/23 (17%) patients are more than 8 genomic alteration detected, 4/23 (17%) patients had 5-8 genetic alteration, remaining 15/23 (67%) patients had less than 4 genetic alteration. Most common SNVs detected included were, CDKN2A- 12/23 patients, PIK3CA-11/23 patients, TP53 -11/23 (87.5%) patients, PTEN -7/23 patients, BRAF-7/23 patients, STK11- 7/23 patients, VHL- 6/23 patients, EGFR, CTNNB1, GNAS, KIT, SMAD3 were 5/23 patients, SMARCB1, SMO, RET, FBXW7, ERBB2, CSF1R, CDH1, APC- 3/23 each, AKT1, EBB4, FGFR3, FGFR3. FLT3, HRAS, JAK3, MET, NOTCH1, NPM1, KRAS, PTPN11- 1 or 2/23 patients. On combination of these genetic alterations - EGFR, KIT, PTEN, PIK3CA, TP 53, VHL are the main alterations and combination of these gene (Govardhan Diagnostic and Screening Genetic Module for Cervix Cancer), at least one genetic alteration among combination was found in 100% patients at any point of time.

Conclusions

CfTDNA can be easily demonstrable and can be used as a noninvasive diagnostic tool in cervical carcinoma. The proposed genetic screening module needs to be further investigated at large scale with different races, ethnicities and countries.

Legal entity responsible for the study

N/A

Funding

None

Disclosure

All authors have declared no conflicts of interest.

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32P - SPARCL1, a novel prognostic predictive factor for GI malignancies: A meta-analysis (ID 1514)

Presentation Number
32P
Presentation Topic
Biomarkers
Lecture Time
13:00 - 13:00
Speakers
  • H. Hu
Authors
  • W. Cai
  • H. Hu
  • W. Ge
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

Secreted protein acidic and rich in cysteines-like 1 (SPARCL1) is abnormally expressed in gastrointestinal (GI) malignancies. However, the correlation between SPARCL1 expression and the prognosis of patients remains unknown. Therefore, we performed a meta-analysis to investigate the potential value of SPARCL1 as a prognostic predictive marker for GI malignancies.

Methods

The PubMed, Embase, EBSCO, CNKI, and Wanfang databases were systematically searched for studies examining SPARCL1 and clinicopathological features, including the prognoses of patients. Hazard ratios (HRs) and odds ratios (ORs) from individual studies were calculated and pooled using a random-effects or fix-effects model. Heterogeneity and publication bias analyses were performed.

Results

Data from 8 studies, including a total of 2,356 patients, were summarized. The expression of SPARCL1 suggested a better prognosis (HR = 0.57, 95% CI: 0.445-0.698, P = 0.000) and was associated with clinicopathological features of GI malignancies, including distant metastasis (OR = 0.44, 95% CI: 0.23-0.85, P = 0.014), lymph node metastasis (OR = 0.56, 95% CI: 0.39–0.81, P = 0.002) and tumor differentiation (OR = 2.21, 95% CI: 1.82–2.69, P = 0.000). Subgroup analyses based on cancer type revealed that the expression of SPARCL1 had no effect on lymph node metastasis in colorectal cancer, and it did not influence tumor differentiation in gastric cancer. (all P > 0.05).

Conclusions

SPARCL1 could be a novel prognostic predictive factor for GI malignancies. The expression of SPARCL1 could influence the clinicopathological features of GI malignancies. Further large-scale studies are essential to confirm SPARCL1’s prognostic predictive value, and more fundamental experimental studies are needed to illustrate the mechanisms.

Legal entity responsible for the study

Hanguang HU

Funding

None

Disclosure

All authors have declared no conflicts of interest.

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33P - Prognostic significance of serum Beta 2 Microglobulin in Non-Hodgkin Lymphoma (ID 1584)

Presentation Number
33P
Presentation Topic
Biomarkers
Lecture Time
13:00 - 13:00
Speakers
  • G. Gupta
Authors
  • G. Gupta
  • V. Ghalaut
  • V. Lokanathan
  • P. Sharma
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

Lymphoma has been described as the proliferation of lymphoid cells, arising as discrete tissue masses. 85% of all the malignant lymphoma are found to be NHL. Beta 2 microglobulin (B2M) is a small (11,800-dalton) protein, present in nearly all nucleated cells and biological fluids, including serum, urine, and synovial fluid. It forms the light chain subunit of the MHC class I antigen. The objective of this study was to determine the role of serum levels of B2M in the prognosis of patients with NHL so as to strengthen its potential role as a convenient non-invasive biomarker.

Methods

Fifty diagnosed cases of NHL and fifty age and sex matched healthy controls were taken. Serum levels of B2M were estimated in newly diagnosed patients before initiating treatment and in controls by ELISA. The patients were treated with CHOP Regimen (cyclophosphamide, hydroxydaunomycin, oncovin, and prednisolone). Serum B2M was estimated again upon completion of six chemotherapeutic cycles.

Results

Serum B2M levels significantly higher (P< 0.01) in NHL patients (5.66±2.14 μg/ml) than in controls (1.47± 0.60 μg/ml); they were also higher in patients in advanced stages (stage III and IV) (8.30±0.096 μg/ml) than those in early (stage I and stage II) (3.4804±.085μg/ml) (P<0.01). The levels significantly decreased after therapy (P< 0.01) and were also lower in patients achieving remission (3.92 ±1.78 μg/ml) than in those who did not show remission (8.52 ± 1.58 μg/ml).

Conclusions

The data obtained shows that serum B2M test can be an important prognostic tool for assessment of treatment response in NHL patients, as serum levels were significantly higher in the pretreatment group than post treatment group; they also declined significantly only in patients achieving remission. Further, as B2M levels were also correlated with advanced stage, they may reflect the total amount or turnover of malignant cells in the body. Therefore, repeated determinations of serum B2M in these patients might be useful as an estimate of the residual malignant cell mass after therapy. Thus, whereas elevated B2M levels indicated high turnover of lymphoma cells, low levels after chemotherapy might indicate the achievement of remission in NHL cases.

Legal entity responsible for the study

PGIMS Rohtak

Funding

None

Disclosure

All authors have declared no conflicts of interest.

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34P - AFR as a prognostic biomarker to predict clinical outcome of NSCLC individuals (ID 1880)

Presentation Number
34P
Presentation Topic
Biomarkers
Lecture Time
13:00 - 13:00
Speakers
  • S. Li
Authors
  • S. Li
  • Y. Jiang
  • X. Wang
  • H. Ying
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

Chronic inflammation is one of the critical causes to promote initiation and metastasis of solid malignancies including lung cancer. Inflammatory biomarkers, fibrinogen (Fib) and albumin (Alb), are significantly correlated with survival of other cancer. Here, we aim to investigate the prognostic roles of Alb to Fib ratio (AFR), Fib and Alb in lung cancer and to establish a novel effective nomogram combined with AFR.

Methods

412 lung cancer (LC) patients diagnosed between Feb 2005 and Dec 2014 were recruited in this retrospective study. the survival data were obtained by 3 years’ following-up. The prognostic roles of AFR, Fib, Alb, NLR, PLR and MLR were identified by X-tile software, Kaplan-Meier curve, Cox regression model and time-dependent ROC.

Results

In our study, the optimal cut-off values of AFR, Fib, Alb, NLR, PLR and MLR were 7.8, 3.3 mg/dL, 39.0 g/L, 2.7, 144.0 and 0.2, respectively. Low AFR (adjusted HR = 1.820, 95%CI=1.250-2.652 for LC; adjusted HR = 2.308, 95%CI=1.478-3.606 for NSCLC), high Fib (adjusted HR = 1.575, 95%CI=1.108-2.238 for LC; adjusted HR = 1.892, 95%CI=1.257-2.846 for NSCLC), low Alb (adjusted HR = 1.524, 95%CI=1.157-2.006 for LC; adjusted HR = 1.811, 95%CI=1.326-2.474 for NSCLC) were significantly associated with increased risk of death for LC patients, especially for NSCLC patients in all stages; high NLR was obviously associated with poor survival in LC individuals (adjusted HR = 1.405, 95%CI=1.066-1.852), particularly NSCLC (adjusted HR = 1.552, 95%CI=1.129-2.133) and TNM IV stage (adjusted HR = 1.92, 95%CI=1.201-3.071) patients, and high PLR (adjusted HR = 1.391, 95%CI=1.064-1.820 for LC; adjusted HR = 2.186, 95%CI=1.186-4.033 for TNM IV stage) was significantly increased risk of death for advanced stage LC patients. Moreover, the area under curves (AUCs) within AFR, Fib, NLR were higher than that within Alb and PLR for prediction of survival of NSCLC patients; c-index of predicted nomogram for NSCLC including AFR was higher than that without these additional parameters (c-index= 0.731 vs.0.719).

Conclusions

Our findings demonstrated that circulating pre-treatment AFR was a promising prognostic biomarker to improve the predicted efficacy of nomogram for NSCLC.

Legal entity responsible for the study

The Ethical Committees of the two hospitals The second Affiliated Hospital of Nanchang University (Jiangxi, China) and The first Affiliated Hospital of Nanchang University (Jiangxi, China).

Funding

The National Natural Science Foundation of China under Grant (No. 81360083, No. 81271912 and No. 81560033); and 2016 Jiangxi Province Postgraduate Innovation Special Fund under Grant (No. YC2016-S057).

Disclosure

All authors have declared no conflicts of interest.

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35P_PR - Analysis of EGFR mutation status in blood and CSF in lung adenocarcinoma patients with EGFR mutation and CNS metastasis by ddPCR (ID 1934)

Presentation Number
35P_PR
Presentation Topic
Biomarkers
Lecture Time
13:00 - 13:00
Speakers
  • Y. Sen
Authors
  • Y. Sen
  • Q. Wang
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

Patients with non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations benefit a great deal from EGFR tyrosine kinase inhibitors(TKIs). However, most patients recrudesce within one or two years, and many of them progress in the central nerve system (CNS). Owing to the blood–brain barrier, detecting tumor-derived cell-free DNA (cfDNA) in the blood of brain metastasis tumor patients is challenging. Detecting tumor-specific mutations in cerebral spinal fluid (CSF) may become an alternative method.

Methods

41 initial or progressed lung adenocarcinoma patients with EGFR mutation and CNS metastasis from Henan Cancer Hospital were included in this study. 41 patients were all detected EGFR mutation status in CSF with dropplet digital PCR (ddPCR) and 37 in 41 patients were detected EGFR mutation status in blood with the same method. Their clinical information were also collected at the same time.

Results

The rate of EGFR mutations in blood (15/41, 36.6%) was obviously higher than that in CSF (24/37, 64.9%) (P = 0.013), especially in those with EGFR exon 19del mutation patients (13/16 vs 7/18, P = 0.017), without EGFR TKIs treated patients (8/11 vs 3/13, P = 0.038) and less than 60 years patients (17/22 vs 10/25, P = 0.010). In patients with CNS symptoms positive, the rate of EGFR mutations in CSF was higher than those negative (13/27 vs 2/14, P = 0.033). In patients with MRI indicating leptomeningeal metastasis, the rate of EGFR mutations in CSF was higher than those not indicating (8/11 vs 7/30, P = 0.003).

Conclusions

The EGFR mutation status in blood are different from that in CSF in patients with EGFR mutations and CNS metastasis. CNS symptoms and MRI indicating leptomeningeal metastasis are closely related with EGFR mutations status in CSF. Detecting EGFR mutation status in both extracranial and intracranial tumors will be helpful to make precise treatment, and detecting in blood and CSF with ddPCR may be an alternative.

Legal entity responsible for the study

The Affiliated Cancer Hospital of Zhengzhou University

Funding

None

Disclosure

All authors have declared no conflicts of interest.

Characteristicn (%)
Gender
Male23 (56.1)
Female18 (43.9)
Age
≥ 6016 (39)
< 6025 (61)
Smoking status
Yes12 (29.3)
No29 (70.7)
Brain metastases (MRI)
Only metastatic tumors30 (73.2)
With meningeal lesions11 (26.8)
Brain metastatic tumor number
Single10 (24.4)
Multiple31 (75.6)
Neurological symptoms
Positive15 (36.6)
Negative26 (63.4)
Prior TKIs treat
Yes28 (68.3)
No13 (31.7)
CSF EGFR mutation
197 (17.1)
216 (14.6)
Both2 (4.9)
Negative26 (63.4)
Blood EGFR mutation
1913 (31.7)
2110 (24.4)
Both1 (2.4)
Negative13 (31.7)

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36P - Prognostic significance of circulating microRNA-155 expression in breast cancer patients (ID 1232)

Presentation Number
36P
Presentation Topic
Biomarkers
Lecture Time
13:00 - 13:00
Speakers
  • P. Yadav
Authors
  • P. Yadav
  • M. Mirza
  • K. Nandi
  • S. Jain
  • R. Kaza
  • N. Khurana
  • A. Saxena
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

Breast cancer (BC) is the leading cause of cancer‐related mortality in the female population. MicroRNA‐155 (miR‐155), an oncogenic non‐coding RNA, plays an important role in the pathogenesis of breast cancer. However, the level of circulating miR-155 expression and its clinical significance are not well established. The aim of present study was to evaluate the prognostic role of circulating miR-155 expression in serum of breast cancer patients.

Methods

Study includes 75 serum samples from histopathologically confirmed, newly diagnosed cases of breast cancer and 75 healthy control subjects. Total RNA from serum was isolated by using Trizol reagent, polyadenylated and reverse transcribed into cDNA. The expression level of miR‐155 was detected by using qRT‐PCR. Relative expression was determined with matched controls using U6 snRNA as a reference. Levels of miRNA expression were compared with distinct clinicopathological features. The total follow-up period was 41 months and mean follow-up time was 28 months. Kaplan-Meier survival analysis was performed for overall survival of breast cancer patients. The study was ethically approved by Institutional Ethics Committee, Maulana Azad Medical College, New Delhi.

Results

The overall relative fold increase of miR‐155 expression in breast cancer patients was 8.80 fold compared to the healthy controls. When the level of miR‐155 expression was compared with distinct clinicopathological features, there was a significant association seen between miR‐155 expression with TNM stage (p = <0.0001), lymph node status (p = 0.007) and distant metastasis (p = 0.001) of breast cancer patients. ROC analysis for prognosis yielded significant AUC values for early vs advanced stages (AUC= 0.742 (95% CI: 0.629-0.855)) and presence vs absence of distant metastasis (AUC= 0.913 (95% CI: 0.838-0.988)) of breast cancer patients. There was a significant association (p = 0.004) found between overall survival and expression of miR‐155 in breast cancer patients.

Conclusions

Our findings suggest that overexpression of serum miR‐155 expression might be a useful, non-invasive, prognostic biomarker for breast cancer patients. A large pool study will be necessary to confirm our findings.

Legal entity responsible for the study

Prof. Dr. Alpana Saxena

Funding

None

Disclosure

All authors have declared no conflicts of interest.

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37P - Association of mammographic density and fibroglandular tissue volume with the subtype of breast cancer (ID 1529)

Presentation Number
37P
Presentation Topic
Biomarkers
Lecture Time
13:00 - 13:00
Speakers
  • W. Shia
Authors
  • W. Shia
  • D. Chen
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

The risk of relapse associated with each breast cancer molecular subtype was determined in a large cohort of patients with breast cancer. In this study, the association of mammographic breast density and fibroglandular tissue volume measures with the subtype of breast cancer will be discussed.

Methods

Total 751 breast cancer patients have full field digital mammography (FFDM) which before surgery and chemotherapy were enrolled from 2011 to 2015. The patients include luminal-like (80.5%), basal-like (14.6%) and HER2-postive subtypes (4.9%). The receptor status was abstracted from clinical pathology records, and supplemented by IHC staining of tumor sections. In these patients, there are 9.76% patients were relapsing and 7.3% patients were metastasized. The breast density and volumetric measure was based on accumulated X-ray doses assessments by Volpara™ (Volpara version 1.4.2, Matakina Technology, NZ). The FFDM image from 58,550 health women enrolled from 2011 to 2015 were also used to generate the normal model and make the comparison baseline. All needed FFDM images were obtained from the Department of Medical Imaging, Changhua Christian Hospital, Taiwan.

Results

The mean breast density of patients with basal-like and HER2-positive are higher than the healthy women density baseline from 3.3% to 5%. The mean fibroglandular tissue volume of patients was significant larger than health women. The mean fibroglandular tissue volume of HER2-positive (66.74 cm3, SD = 8.12) and basal-like patients (81.04 cm3, SD = 33.37) was significant larger than the volume of luminal-A (46.04 cm3, SD = 28.87) and luminal-B patients (41.71 cm3, SD = 18.55), and also larger than the mean fibroglandular tissue volume of health women from age 45 to 65 (38.36 cm3, SD = 20.47).

Conclusions

Because of the breast tissue composition, the variation of breast density and fibroglandular tissue volume can be the good predictor in cancer risk and for the subtype classification, especially from breast cancer patients with HER2-positive and basal-like subtype.

Clinical trial identification

This study was approved by the Institutional Review Board of Changhua Christian Hospital, Taiwan (No. 160110).

Legal entity responsible for the study

Department of Research, Changhua Christian Hospital

Funding

None

Disclosure

All authors have declared no conflicts of interest.

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38P - A novel ADS prognostic score containing prospective AFR, Alb and dNLR predicted overall survival in esophageal cancer patients (ID 1616)

Presentation Number
38P
Presentation Topic
Biomarkers
Lecture Time
13:00 - 13:00
Speakers
  • Q. Gao
Authors
  • Q. Gao
  • X. Huang
  • J. Qiu
  • H. Ying
  • X. Wang
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

Inflammation was identified to play a significant effect on progression and prognosis of esophageal cancer (EC). In current study, we investigated the prognostic value of fibrinogen (Fib), albumin (Alb), Alb-Fib ratio (AFR) and circulating blood ratios (NLR, dNLR, PLR and LMR) in patients with EC undergoing esophagectomy.

Methods

A total of 153 EC patients were included in present study, and all of them were clinical confirmed and underwent esophagectomy between January 2011 and December 2013. We detected the preoperative circulating Alb, Fib and counts of white blood cells (neutrophil, monocyte, lymphocyte and platelet), and obtained the survival data by 3 years’ following-up in the cases. X-tile software, Kaplan-Meier curve, Cox regression and predicted nomogram were used to evaluate the prognostic role of them in EC patients.

Results

The optimal cut-off points of Fib, Alb, AFR, NLR, dNLR, PLR and LMR were 3.2mg/dl, 38.2g/l, 9.3, 2.1, 4.3, 145.9 and 2.3, respectively. AFR(<9.3), Alb(<38.2g/L), Fib(≥3.2mg/dl), dNLR(≥4.3), PLR(≥145.9) and LMR(<134) were significantly associated with decreased 3 years’ overall survival(OS) in univariate analysis, and AFR ((adjusted HR(95%CI)=2.381(1.152-4.926)), Alb ((adjusted HR(95%CI)=2.398 (1.342-4.273)), Fib ((adjusted HR(95%CI)=2.148(1.229-3.753)), dNLR ((adjusted HR(95%CI)= 2.938(1.626-5.308)) and PLR ((adjusted HR(95%CI) =1.964(1.129-3.415)) remained significant in multivariate analysis. The results of time-dependent receiver operating characteristics curve showed that AFR, dNLR and Alb shared the higher survival predicted efficacy comparing to Fib and PLR. We identified that the prognostic ADS score depending on AFR, Alb and dNLR ((adjusted HR(95%CI) for 1 and 2 score were 3.197(1.813-5.639) and 12.711(2.756-58.614), respectively) and modified ADS score (mADS) ((adjusted HR(95%CI) for 1 and 2 score were 2.725(1.474-5.041) and 9.195(2.048-41.278), respectively) were independent prognostic factors for EC. Moreover, EC patients with higher ADS score could benefit from the adjuvent radio-chemotherapy, however, there was no significant survival difference in EC patient harbored 0, 1 and 2 ADS scores without treatment of radio-chemotherapy. Additionally, we observed a significant difference in c-index values of estimated nomograms including or without ADS score.

Conclusions

Preoperative ADS score including AFR, Alb and dNLR was a prospective biomarker to predict clinical efficacy of adjuvent radio-chemotherapy and 3 year’ OS, and the nomogram including the score obviously improved the predicted survival efficacy for surgically resected EC patients.Preoperative ADS score including AFR, Alb and dNLR was a prospective biomarker to predict clinical efficacy of adjuvent radio-chemotherapy and 3 year’ OS, and the nomogram including the score obviously improved the predicted survival efficacy for surgically resected EC patients.

Legal entity responsible for the study

Medical Ethics Committee of the Second Affiliated Hospital of Nanchang University (Jiangxi, China).

Funding

None

Disclosure

All authors have declared no conflicts of interest.

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39P - Brain metastases-related microRNAs in the advanced breast cancer patients (ID 1952)

Presentation Number
39P
Presentation Topic
Biomarkers
Lecture Time
13:00 - 13:00
Speakers
  • J. Sato
Authors
  • J. Sato
  • A. Shimomura
  • J. Kawauchi
  • J. Matsuzaki
  • S. Takizawa
  • H. Sakamoto
  • M. Ohno
  • Y. Narita
  • K. Tamura
  • T. Ochiya
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

Among advanced breast cancer patients, brain metastases are a major distant metastasis and associated with poor prognosis. MicroRNAs have a great influence on various oncological functions and have been reported as a potential biomarker for detecting distant metastases. Specific biomarkers and unique mircoRNAs for brain metastases have not yet been reported. The aim of this study was to explore novel microRNAs in serum for leading to brain metastases in the patients with advanced breast cancer using mircoRNA array-based approach.

Methods

We retrospectively analyzed the medical records of breast cancer patient and collected clinical data and evaluate the serum microRNA profiles between breast cancer patients with brain metastases and without brain metastases using highly sensitive microarray analysis. All patients underwent brain imaging tests (computed tomography or magnetic resonance imaging). The samples were divided into a training cohort and a test cohort in 2:1 ratio. The training cohort was used to identify microRNAs that could detect brain metastases of breast cancer, and the test cohort was used to validate that microRNAs.

Results

A total of 51 serum samples of breast cancer patients with brain metastases stored in the National Cancer Center Biobank were used. In addition, 28 serum samples were obtained from non-brain metastasis controls. The results showed that two microRNAs (miR-A and miR-B) were found to be able to detect brain metastases of breast cancer. No significant correlation was found between miR-A expression in serum and clinical data. miR-B expression in serum was significantly related to estrogen-receptor (ER) expression in primary breast cancer tissue (P < 0.05).

Conclusions

Serum miR-A and miR-B might be a useful biomarker for predicting brain metastases in breast cancer patients.

Legal entity responsible for the study

N/A

Funding

None

Disclosure

A. Shimomura: I have the following financial relationships to disclose Research funding by AstraZeneca. J. Kawauchi, S. Takizawa: Employee of Toray Industries, Inc. K. Tamura: I have the following financial relationships to disclose. Direct research support to the responsible project lead by Daiichisankyo, MSD, pfizer, AstraZeneca. T. Ochiya: I have the following financial relationships to disclose. Grant/Research funding from: Kyowa Medex, Kewpie Corporation, Takeda, Rohto Pharmaceutical Co., Ltd., Japan Atherosclerosis Research Foundation, Inter Stem, BioMimetics Sympathies. All other authors have declared no conflicts of interest.

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40P - Cell-free microRNA‐200c expression as a prognostic/predictive biomarker in breast cancer patients (ID 961)

Presentation Number
40P
Presentation Topic
Biomarkers
Lecture Time
13:00 - 13:00
Speakers
  • M. Masroor
Authors
  • M. Masroor
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

Breast cancer in women is an important cause of cancer‐related mortality. MicroRNA‐200c (miR‐200) is important in the epithelial to mesenchymal transition (EMT) and plays a major role in breast cancer metastasis. The present study focused on investigating the prognostic importance of cell-free miR‐200c expression in breast cancer patients.

Methods

A total of 75 histopathologically confirmed newly diagnosed breast cancer female subjects as well as 75 healthy controls were included. Blood samples of subjects were collected in serum vial and total RNA from serum was isolated by using Trizol reagent. Total RNA was polyadenylated and reverse transcribed into cDNA. Expression level of miR‐200c was detected by using miRNA qRT‐PCR. Relative expression was determined with matched controls using U6 snRNA as reference. Levels of miRNA expression was compared with distinct clinicopathological features. Total follow up period was 41 months and mean follow up time was 28 months. Kaplan Meier survival testing was performed to calculate the overall survival of breast cancer patients. The study was ethically approved by Institutional Ethics Committee, Maulana Azad Medical College, New Delhi.

Results

The overall relative fold increase of miR‐200c expression was 8.80-fold in breast cancer patients compared to the healthy controls. Level of cell free miR‐200c expression was compared with distinct clinicopathological features. There was a significant association was found between miR‐200c expression with TNM stage (p = <0.0001), histological grade (p= 0.006), lymph node status (p= 0.006) and distant metastasis (p= 0.006) in breast cancer patients. ROC curves for prognosis yielded significant AUC values for early vs advanced stage, histological grade, lymph node involvement, and distant metastasis. There was a significant association (p= 0.006) found between overall survival and expression of miR‐200c in breast cancer patients.

Conclusions

The study revealed that the cell-free miR‐200c overexpression may be a useful, noninvasive, prognostic and predictive biomarker for breast cancer patients. A large pool study would be necessary to confirm our findings.

Clinical trial identification

NA

Legal entity responsible for the study

Dr Alpana Saxena

Funding

None

Disclosure

All authors have declared no conflicts of interest.

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41P - Biomarker analysis of TPD regimen (trastuzumab, ertuzumab and docetaxel) for advanced HER2-positive breast cancer by HER family expression (ID 1169)

Presentation Number
41P
Presentation Topic
Biomarkers
Lecture Time
13:00 - 13:00
Speakers
  • K. Takada
Authors
  • K. Takada
  • S. Kashiwagi
  • Y. Asano
  • W. Goto
  • T. Takashima
  • T. Morisaki
  • S. Noda
  • N. Onoda
  • K. Hirakawa
  • M. Ohira
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

The TPD regimen (trastuzumab, pertuzumab and docetaxel) is strongly recommended as a treatment option for first-line therapy for advanced human epidermal growth factor receptor (HER) 2-positive breast cancer (BC). BC is a very diverse disease regarding tumor biology with wide variation among individuals regarding sensitivity to anticancer drugs. Accordingly, to achieve maximum results from chemotherapy, it is necessary to predict the efficacy of treatment and select the optimum pharmacotherapy according to the characteristics of both the patient and the tumor. There is therefore a need for the identification of useful biomarkers that are capable of predicting the therapeutic effect when advanced HER2-BC is treated with the TPD regimen. In this study, we analyzed the expression of HER 1–4 proteins, and investigated whether or not their expression was predictive of the response of advanced HER2-BC to the TPD regimen.

Methods

The subjects consisted of 29 cases in which TPD regimen chemotherapy was carried out. The expression levels of estrogen receptor (ER), progesterone receptor (PgR), Ki67, HER1-4 were evaluated using immunostaining employing needle biopsy specimens.

Results

The HER1, HER3 and HER4 cut-off value for progression-free survival (PFS) was 28.6 (area under ROC curve (AUC), 0.566; sensitivity, 61.11%; specificity, 72.73%), 33.9 (AUC, 0.533; sensitivity, 83.33%; specificity, 54.55%), and 65.4 (AUC, 0.629; sensitivity, 61.11%; specificity, 72.73%), respectively. Of the 29 HER2-BC patients, 14 (48.3%) were in the HER1 positive group, 19 (65.5%) were in the HER3 positive group, and 14 (48.3%) were in the HER4 positive group. The overall response rate (ORR) was significantly higher in the HER3 positive group than in the HER3 negative group (p = 0.002). In prognostic analysis, the HER3 positive group showed a significant PFS extension over the HER3 negative group (p = 0.042, log-rank). In univariate analysis, a high ORR (p = 0.004, hazard ratio=0.123) and positive HER3 expression (p = 0.023, hazard ratio=0.279) significantly contributed to extension of the PFS interval.

Conclusions

HER3 expression may be a useful factor for predicting the response of HER2-BC to the TPD regimen.

Legal entity responsible for the study

Department of Surgical Oncology, Osaka City University Graduate School of Medicine

Funding

None

Disclosure

All authors have declared no conflicts of interest.

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42P - New candidate biomarkers discerning benign liver tumors from hepatocellular carcinoma (ID 1386)

Presentation Number
42P
Presentation Topic
Biomarkers
Lecture Time
13:00 - 13:00
Speakers
  • A. Budko
Authors
  • A. Budko
  • M. Chesnokov
  • P. Skovorodnikova
  • D. Shavochkina
  • I. Kustova
  • N. Kudashkin
  • Y. Patyutko
  • N. Lazarevich
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

Hepatocellular carcinoma (HCC) is the most common form of malignant liver tumors, characterized by unfavorable prognosis and low sensitivity to chemotherapy. HCC diagnosis is complicated by late manifestation of symptoms and lack of effective biomarkers. The existing MRI approach does not cover 20% of HCC cases (hypovascular variants). Another problem is differential diagnosis between G1-stage HCC and subclasses of hepatocellular adenoma (HCA). Present study examines the ability of potential biomarkers, previously identified by our group, to differentiate HCC from benign liver tumors represented by HCA and focal nodular hyperplasia (FNH). We also analyzed gene expression changes associated with the development of FNH and HCA in order to identify molecular markers capable of distinguishing between these two neoplasm types.

Methods

61 pairs of surgical biopsies of tumor and non-tumorous liver tissue of patients with HCA (5 cases), FNH (6 cases) and HCC (50 cases) were used in the study. Expression levels of RAB3B, IQGAP3, GPC3, HKDC1, TOP2A, GNAZ, PDGFA and CENPF genes were evaluated using RT-qPCR. Data on gene expression changes were statistically processed and sorted using hierarchical cluster analysis.

Results

Significant (p < 0.05) increase in expression level of IQGAP3 (p = 8.8x10−8), GPC3 (p = 4.2x10−5), CENPF (p = 5.1x10−4), and TOP2A (p = 0.042) was detected in HCC tissue but not in benign tumor samples when compared to respective non-tumor samples. HKDC1 and RAB3B overexpression was observed in both HCC and benign tumors. HCA and FNH cases differ considerably by pattern of gene expression changes. HKDC1 expression level is higher in FNH than in HCA (p = 0.017).

Conclusions

Overexpression of IQGAP3, GPC3, CENPF and TOP2A genes is specific for HCC, but not HCA and FNH, so these genes are promising candidate biomarkers for differential diagnosis of benign and malignant liver tumors. Activation of RAB3B and HKDC1 genes in FNH and HCA tissue suggests their possible role in the development of these neoplasms. Specific patterns of gene expression changes described for HCA and FNH indicate the difference in molecular mechanisms underlying their pathogenesis and provide a tool for distinguishing these neoplasms from each other.

Legal entity responsible for the study

Prof. Natalia L. Lazarevich, PhD, DSc Head of Laboratory of Epithelial Tumors Progression Mechanisms, Institute of Carcinogenesis, N.N. Blokhin Russian Cancer Research Center of Russian Ministry of Health, Moscow, Russian Federation.

Funding

None

Disclosure

All authors have declared no conflicts of interest.

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43P - Loss of CDKL2 expression correlates with differentiation, stage, and poor prognosis of gastric cancer (ID 1533)

Presentation Number
43P
Presentation Topic
Biomarkers
Lecture Time
13:00 - 13:00
Speakers
  • K. Lin
Authors
  • K. Lin
  • Y. Uen
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

Gastric cancer (GC) remains a major public health problem throughout the world. In this study, we investigated the involvement of a new member of cyclin-dependent kinases, cyclin-dependent kinase-like 2 (CDKL2) in tumor progression, and in the prognosis of human GC.

Methods

The patient cohort in this study consisted of 151 GC cases, documenting pathologic and clinical factors, as well as clinical outcomes. Immunohistochemistry and immunoblotting were employed to examine the CDKL2 expression in 151 pairs of normal and GC tissues and 5 gastric cells. Based on the expression of CDKL2, two GC cell with low CDKL2 level was chosen for CDKL2 overexpression. The effect of CDKL2 overexpression on the growth of CDKL2-manupulated GC cells was examined.

Results

Downregulation of CDKL2 protein was observed in 83 patients and was significantly correlated with Lauren classification, staging, degree of differentiation, and poor disease-free survival. Univariate Cox regression analysis showed that loss of CDKL2 is a prognostic marker for GC. Furthermore, CDKL2 expression was suppressed in several GC cells. In vitro experiments indicated that CDKL2 overexpression inhibited GC cell growth.

Conclusions

This study suggests that loss of CDKL2 can be a useful marker for predicting the outcome of GC patients.

Clinical trial identification

Not applicable.

Legal entity responsible for the study

The institutional review board at Chi-Mei Medical Center

Funding

Chi-Mei Medical Center

Disclosure

All authors have declared no conflicts of interest.

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44P - Genomic analysis, biomarker and PDL1 expression in NUT midline carcinoma (ID 1539)

Presentation Number
44P
Presentation Topic
Biomarkers
Lecture Time
13:00 - 13:00
Speakers
  • S. Chouial
Authors
  • S. Chouial
  • A. Mustafa
  • J. Xiu
  • S. Rashad
  • H. Aboud
  • A. Bulbul
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

Nuclear protein in testis midline carcinoma (NMC) is a very rare, aggressive subset of poorly differentiated squamous cell malignancy with a dismal 6.7-month median survival and usually occur in the midline anatomical structures of Head & neck, mediastinum. BRD4–NUT rearrangement is pathognomonic. BRD4 can up-regulate the expression of PD-L1 and Bromodomain inhibitors (BETi) currently in trials suppress PDL1 expression and tumor growth (Zhu, Cell Rep; 2016). We, therefore, attempted to study the comprehensive landscape of genomic alterations and PDL1 expression pattern.

Methods

We investigated three NMC cases that underwent molecular profiling using a commercial multiplatform profiling service (Caris Life Sciences, Phoenix, AZ). We sequenced genomic DNA isolated from a formalin-fixed paraffin embedded tumor sample using the Illumina NextSeq platform (NextGen), protein expression (IHC) and gene amplification (CISH or FISH), antibody used for PD-L1 is SP142 (tumor cell). ArcherDx FusionPlex Assay was used for gene fusions.

Results

All three cases were identified with NUTM1 fusions (BRD3-NUTM1 fusion in one case and BRD4-NUTM1 fusion in 2). Patients aged between 34-44. High PDL1 Expression (3+, 100%) was seen in one tumor, median tumor mutational load was 5 mutations/megabase (low; range: 2-6). ERCC1 expression was low in all (3/3), while high TOPO1 expression in (2/3) and TOP2A in 2/2. RRM1 expression was negative in (2/3) High expression of TUBB3 was seen in (2/3). 592 genes were analyzed and no additional pathogenic alterations were identified using a 592-gene mutation panel.

Conclusions

High PDL1 expression may be present in some NMC tumors despite simple molecular karyotype and low tumor mutational burden. Anthracyclines, platinum compounds, TOPO1 inhibitors, taxanes and gemcitabine may be useful for inducing brief rapid responses based on biomarker expression. (BETi) and histone deacetylase inhibitors (HDACi), currently in clinical trials can induce differentiation and growth arrest of NMC cells. BETi combined with PD-1/PD-L1 targeted therapy may be a promising future for NMC by suppressing PDL1 to increase the activity of anti-tumor cytotoxic T cells and restore anti-tumor immunity.

Legal entity responsible for the study

Kymera Independent Physicians

Funding

None

Disclosure

All authors have declared no conflicts of interest.

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45P - Frequencies and expression levels of programmed death ligand 1 (PD-L1) in circulating tumor RNA (ctRNA) in various cancer types (ID 1811)

Presentation Number
45P
Presentation Topic
Biomarkers
Lecture Time
13:00 - 13:00
Speakers
  • T. Ishiba
Authors
  • T. Ishiba
  • K. Danenberg
  • J. Usher
  • T. Nakagawa
  • G. Oda
  • H. Uetake
  • N. Hoshino
  • Y. Nishioka
  • T. Kawano
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

Precision medicine and prediction of therapeutic response requires monitoring potential biomarkers before and after treatment. Liquid biopsies provide noninvasive prognostic markers such as circulating tumor DNA and RNA. Circulating tumor RNA (ctRNA) in blood is also used to identify mutations in genes of interest, but additionally, provides information about relative expression levels of important genes. In this study, we analyzed PD-L1 expression in ctRNA isolated from various cancer types. Tumors inhibit antitumor response by modulating the immune checkpoint proteins programmed death ligand 1 (PD-L1) and its cognate receptor PD1. The expression of these genes has been implicated in evasion of immune response and resistance to targeted therapies.

Methods

Blood samples were collected from gastric (GC), colorectal (CRC), lung (NSCLC), breast (BC), prostate cancer (PC) patients, and a healthy control group. ctRNA was purified from fractionated plasma, and following reverse transcription, levels of PD-L1 expression were analyzed using qPCR.

Results

PD-L1 expression was detected in the ctRNA of 33.3% (3/9 plasma samples) of GC patients, 23.4% (22/94) of CRC patients, 39% (16/41) of NSCLC patients, 54.5% (6/11) of BC patients and 35.3% (6/17) of PC patients. PD-L1 mRNA was not detected in the cancer-free group (0/9), but this was not significantly different from the cumulative cancer patients (p = 0.0602, Fisher’s Exact Test). The frequency of PD-L1 expression was significantly different among the cancer types we studied (p < 0.0001, Fisher ’s Exact). However, median relative PD-L1 expression was not statistically significantly different (7.0 in GC, 5.6 in CRC, 10 in NSCLC, 7.8 in BC, and 9.1 in PC) (p = 0.258, Median Test).

Conclusions

PD-L1 mRNA can be detected and quantitated in ctRNA of cancer patients. The frequency of PD-L1 expression varies by cancer type, however, when detected in ctRNA, levels of PD-L1 expression do not significantly differ across these cancers. These results pave the way for further studies aimed at determining whether monitoring the levels of PD-L1 mRNA in blood can identify patients who are most likely to benefit from the conventional treatment.

Legal entity responsible for the study

Liquid Genomics, Inc.

Funding

None

Disclosure

All authors have declared no conflicts of interest.

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46P - The frequency of somatic AKT1 mutation among Japanese breast and endometrial cancer patients (ID 2081)

Presentation Number
46P
Presentation Topic
Biomarkers
Lecture Time
13:00 - 13:00
Speakers
  • T. Seo
Authors
  • T. Seo
  • T. Shimoi
  • A. Hamada
  • A. Shimomura
  • K. Sudo
  • E. Noguchi
  • K. Yonemori
  • C. Shimizu
  • Y. Fujiwara
  • K. Tamura
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

The PI3K/AKT/mTOR pathway is frequently activaed across many cancers. AKT1 is a subfamily of serine/threonine protein kinases, affecting cell survival, proliferation and invasion. The prior reports from Western country have shown AKT1 mutation in 3-6% of breast cancer and in 2-3% of endometrial cancer. However, the clinico-pathological features of AKT1 E17K mutation in Asian female cancers is unclear. In this study, we examined breast cancer samples and endometrial cancer samples for mutation in AKT1 hotspot at our institution.

Methods

For patients with breast cancer and endometrial cancer, we retrospectively analyzed tissue samples preserved between January 2008 and June 2015 in a biobank at national cancer center hospital. We extracted DNA and determined AKT1 mutation with PNA-LNA clamp methods. Kaplan-Meier analysis was performed to analyze relapse-free survival (RFS) after surgery and overall survival (OS) for breast cancer patient.

Results

A total of 469 patients were analyzed. Three hundred and twenty-nine patients were breast and 140 were endometrial cancer. The median age was 52 (range 22-90). In breast cancer patients, 305 patients were initially stage I to III, and thirty-two patients were initially Stage IV. The number of tumor subtype was hormone receptor (HR) positive and HER2 negative tumor; 248 (74%), HR positive and HER2 positive tumor; 44 (13%), HR negative and HER2 positive tumor; 28 (8%), and Triple negative tumor; 17 (5%), respectively. We detected AKT1 mutation in 24 patients (7.3%) of breast-cancer patients and 7 patients (5.0%) of endometrial-carcinoma patients. In breast cancer patients, there were 176 relapses and 32 deaths. Median RFS was 79 months in patients with AKT1 wild type and 75 months in patients with AKT1 mutation (p-value:0.77).

Conclusions

We detected AKT1 mutation in 31 patients (6.6%) of 469 breast and endometrial cancer. RFS in breast cancer patients is not significantly different by AKT1 mutation status.

Legal entity responsible for the study

National Cancer Center Hospital

Funding

None

Disclosure

All authors have declared no conflicts of interest.

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47P - Study of tumor immune contexture in patients with squamous carcinomas of head and neck in the Indian population – A pilot study (ID 2093)

Presentation Number
47P
Presentation Topic
Biomarkers
Lecture Time
13:00 - 13:00
Speakers
  • M. Venkata
Authors
  • M. Venkata
  • B. Saha
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

Head and neck squamous cell carcinoma (HNSCC) in India is strongly associated with use of tobacco and areca nut products. Most patients present in their fifth and sixth decades at advanced stages, compared with age at onset in the North American population. These differences in etiology and onset suggest potential differences in pathogenesis and immuno-biology. During immune evasion by tumor, receptors such as CTLA-4, LAG-3, TIM-3, and programmed cell death protein 1 (PD-1), have been identified on exhausted and dysfunctional lymphocytes and shown to be upregulated in tumor cell lines and tissues by transcriptional methods. However, there is limited information currently available in the Indian population in this regard. In our study we intended to define the immune contexture in HNSCC cases by characterizing the tumor infiltrating lymphocytes (TILs) and the intra-tumoral heterogeneity of other relevant markers by immunohistochemistry (IHC) methods. Determining the prognostic and predictive value of these markers may guide the development of drugs for this cancer type, as it has for other carcinomas. It could help clinicians better predict clinical outcomes and thereby make more informed therapeutic decisions.

Methods

50 cases of HNSCC were studied for expression of immune cell markers such as PDL1, IDO, CD8, FOXP3, LAG-3 by IHC methods on formalin fixed paraffin embedded (FFPE) sections. The whole slide images of the stained slides were analyzed manually and by digital algorithms. Frequency and intensity of PDL1 and IDO were evaluated in both immune cells (IC) and tumor cells (TC). Proximity analyses between PDL1+ IC /IDO+IC with FOXP3+ IC /CD8+ IC/ CD3+ IC were performed using standard morphometric approaches and the pattern of immune cell infiltration documented.

Results

Preliminary analysis reveals high concordance between pathologists for all markers and between manual and digital scoring methods. Significant positive correlation between FOXP3+ IC and PDL1+ IC and IDO+ TC with FOXP3 IC is seen with overall percentage of PDL1 and FOXP3 positive immune cells being low as compared to IDO and CD8.

Conclusions

As these changes, at least in part, mirror the immune contexture of HNSCC studied in the North American population, it is surmised that treatment approaches based on PD1 blockade are likely to also provide significant benefit to Indian patients. More detailed analysis is being done. Data will be correlated with pathological stage, tumor and serum kynurenine levels, and two year follow up information, wherever available. Some of this work is being presented here.

Disclosure

All authors have declared no conflicts of interest.

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48P - Genetic association of matrix metalloproteinase MMP- 1, MMP-3 and MMP-9 genes with HCV-related hepatocellular carcinoma in Egyptian patients (ID 985)

Presentation Number
48P
Presentation Topic
Biomarkers
Lecture Time
13:00 - 13:00
Speakers
  • A. Alhanafy
Authors
  • A. Alhanafy
  • B. Montaser
  • W. Fathy
  • N. Elabd
  • S. Tayel
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

Hepatocellular carcinoma (HCC) is one of the most frequent cancers in Egypt in which there is high prevalence of hepatitis C virus (HCV) infection. Matrix metalloproteinases (MMPs) are multifunctional proteins that assume an urgent part in cell development, differentiation, inflammation and angiogenesis. MMPs gene polymorphism might be included in development of HCV-related HCC. The study expected to explore relationship of MMP-1,3 & 9 genes polymorphisms with liver cirrhosis and HCC patients.

Methods

This study included 128 individuals who were enrolled from Menoufia University Hospital in the period between October 2015 and August 2016 classified into the following; Group I: included 48 patients with HCC on top of liver cirrhosis, they were 26 males and 22 females with mean age (58.60±5.29); Group II: 50 patients with liver cirrhosis, they were 26 males and 24 females with mean age (56.74±5.21); and Group III: 30 healthy subjects as controls, they were 15 males and 15 females with mean age (56.30 ±7.30). Diagnosis of HCC was done by their characteristic features in two imaging methods (abdominal US & triphasic CT). All subjects except controls were positive for serum HCV RNA. Liver functions tests, AFP & CHILD score were assessed. Genes polymorphisms were made by PCR-RFLP.

Results

HCC patients had higher mutant G2G2 (35.4%) and G2 allele (62.5%) of MMP-1 gene than both cirrhotic (P < 0.05) and control groups (P < 0.001). For MMP-3 gene, additionally, HCC patients had the most noteworthy predominance of mutant 5A/5A (22.9%) and 5A allele (52.1%) than both cirrhotic (P < 0.05) and control groups (P < 0.001). The results of MMP-9 gene uncovered higher frequency of mutant TT genotype and T allele in both HCC (56.3% and 74%, respectively) and cirrhotic groups (10% and 35%, respectively) than in the control group. In HCC patients, we detected a significant correlation between heterozygote G1/G2 and G2/G2 of MMP-1 gene and homozygote TT of MMP-9 with higher CHILD score, tumor size and stage (P < 0.05). Moreover, MMP-3 5A/6A had higher CHILD score, portal vein thrombosis and advanced stage (P < 0.05) compared with other genotypes.

Conclusions

MMP-1, 3, 9 gene mutation may be embroiled in progression of liver cirrhosis and hazard relationship for HCC development.

Legal entity responsible for the study

Menoufia University

Funding

None

Disclosure

All authors have declared no conflicts of interest.

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49P - Circulating cell-free DNAas a biomarker in the serum of colorectal cancer patients (ID 990)

Presentation Number
49P
Presentation Topic
Biomarkers
Lecture Time
13:00 - 13:00
Speakers
  • A. Alhanafy
Authors
  • A. Alhanafy
  • M. El Shafei
  • M. Safan
  • E. Elnour
  • M. Habib
  • T. Rageh
  • A. Salah El-Din
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

Cell-free DNA is extracellular nucleic acids found in cell-free plasma/serum of humans. Circulating extracellular DNA can be found in healthy persons, persons with nonmalignant diseases, as well as persons with various malignancies. Given the recent approval of a liquid biopsy, the use of circulating tumor DNA as a novel and non-invasive test for the diagnosis and surveillance of cancer is a rapidly growing area of interest.

Methods

This study was carried out in Menoufia University hospital in the period from May 2015 to December 2015. It was conducted on 80 individuals classified into: Group I: included 40 colorectal cancer (CRC) patients Group II: included 20 patients with colorectal benign diseases. Group III: included 20 healthy controls. Laboratory investigations including detection of quantitative analysis of circulating cell free DNA (ccf-DNA) through detection of short (115bp) DNA fragments in serum by real time quantitative PCR by amplifying the ALU repeats (ALU-qPCR) and CA19 9 serum level by ELISA.

Results

There was significant statistical difference in serum level of ALU 115 between group I (1123.8±356.3) and both of group II (432.2±147.8) and III (317±105) both (p = 0.001), where there was non-significant statistical difference in serum levels ALU 115 between group II & III (p = 0.180). There was significant statistical difference in serum level of CA19-9 between group I (42.4±92.3) and both of group II (10.5±5.87) (p = 0.032) and III (9.74±5.62) (p = 0.013), where there was non-significant statistical difference in serum levels of CA19-9 between group II & III (p = 0.684). The diagnostic accuracy for distinguishing primary CRC patients from normal control by ALU 115 is (85%), with sensitivity (83%), specificity (90%), positive predictive value (96%) and negative predictive value (64%) at cut off point of 426 ng/ml. The diagnostic accuracy by CA19-9 is (59%), with sensitivity (60%), specificity (55%), positive predictive value (80%) and negative predictive value (31%) at cut off point of 8.45 U/ml. combined detection of ALU115 and CA19-9 improved the sensitivity to (88%). There was a significant positive correlation between ALU 115 serum level and tumor grade (p = 0.024), also between CA19-9 and primary tumor stage and presence of metastases (p = 0.012) and (p = 0.044).

Conclusions

It was concluded that serum DNA concentrations may be valuable in early diagnosis and monitoring of colorectal cancer patients.

Legal entity responsible for the study

Menoufia University

Funding

None

Disclosure

All authors have declared no conflicts of interest.

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50P - TLE3 expression and the survival rates of patients with advanced serous ovarian cancer (ID 1462)

Presentation Number
50P
Presentation Topic
Biomarkers
Lecture Time
13:00 - 13:00
Speakers
  • H. Anishchanka
Authors
  • H. Anishchanka
  • S. Shelkovich
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

It was previously shown that transducin-like enhancer of split 3 (TLE3) is associated with outcome in patients with taxane-treated breast cancer and endometrioid ovarian cancer (OC). In the present work we assessed the association between TLE3 expression and survival rates in patients with serous ovarian carcinoma.

Methods

100 patients diagnosed with primary serous advanced EOC, underwent complex therapy in Minsk city oncologic center in 2007-2011. Immunohistochemical staining of TLE3 was performed on tissue obtained from the surgical resection. The tumor was considered TLE3-positive when stained with more than 30% of the nuclei.

Results

5-year overall survival (OS) was 0,480 (95% CI [0,379; 0,609]), the median lifetime – 45,5 months. The progression free survival (PFS) was 0,301 (95% CI [0,220; 0,412]). The TLE3 positive tumors were revealed in 19%. PFS was 0,490 (95% CI [0,287; 0,837] in cases with positive tumors in compare with 0,261 (95% CI [0,179; 0,380]) – in negative tumors (P = 0,023). OS was 0,756 (95% CI [0,574; 0,996]) in TLE3 positive cases and 0,434 (95% CI [0,326; 0,578]) - in negative (P = 0,095). All patients with TLE3 positive tumors underwent platinum based chemotherapy and taxanes. In the group with TLE3 negative tumors both platinum based regimens were used – with taxanes or cyclophosphamide. 5-year PFS was similar in the groups – 0,261 (95% CI [0,172; 0,394]) and 0,250 (95% CI [0,094; 0,666]) (P = 0,070), OS – 0,449 (95% CI [0,331; 0,607]) and 0,400 (95% CI [0,196; 0,818]) (P = 0,248).

Conclusions

Determination of TLE3 expression in the resected tumor is necessary for predicting tumor response to chemotherapy. Positive TLE3 expression can serve as the indication for the inclusion of taxanes in the adjuvant chemotherapy schemes. Negative TLE3 expression is a factor of poor prognosis both when using taxanes, and when using cyclophosphamide. Therefore, treatment of this category of patients should start with second-line regimens.

Legal entity responsible for the study

Belarusian Medical Academy of Postgraduate Education, Department of Oncology

Funding

Belarusian Medical Academy of Postgraduate Education

Disclosure

All authors have declared no conflicts of interest.

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51P - Prognostic merit of glucose transporter GLUT1 expression status in gastric cancer (ID 1621)

Presentation Number
51P
Presentation Topic
Biomarkers
Lecture Time
13:00 - 13:00
Speakers
  • J. Wang
Authors
  • J. Wang
  • X. Ying
  • L. Wang
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

Glucose transporter 1 (GLUT1), encoded by the SLC2A1 gene, is a vital element in the glucose transport of malignant cells, and abnormally expressed in a great number of human solid cancers. But the association between GLUT1 overexpression and clinical outcome in gastric cancer setting remains to be clarified. Therefore, we carried out this study to evaluate the correlation between GLUT1 expression and clinicopathological and prognostic characteristics in gastric cancer.

Methods

The mRNA level of GLUT1 expression in different subtypes of gastric cancer was assessed by using Oncomine database. The correlation between GLUT1 expression levels and clinical survival in gastric cancer patients with diverse clinicopathologic parameters was analyzed by using Kaplan-Meier plotter database. The COSMIC and cBioPortal databases were used for analysis of GLUT1 mutation characteristics and alteration frequency.

Results

Oncomine database showed elevated expression of GLUT1 in different subtypes of gastric cancer. Prognostic analysis revealed that elevated expression status of GLUT1 mRNA was associated with poor overall survival and first progression survival of gastric cancer patients. Low alteration frequency was observed in gastric cancer.

Conclusions

GLUT1 is upregulated in gastric cancer, and its overexpression is related with unfavorable clinical survival, indicating that GLUT1 expression is a significant prognostic biomarker of gastric cancer.

Legal entity responsible for the study

Dr. Ji Wang

Funding

National Natural Science Foundation of China (No. 81602471 and No. 81672729) and by grant from Sub project of China National Program on Key Basic Research Project (973 Program) (No. 2014CB744505).

Disclosure

All authors have declared no conflicts of interest.

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Biomarkers Poster lunch Poster Display session

52P - FPR as a prognostic biomarker in stage II and III gastric cancer (ID 1646)

Presentation Number
52P
Presentation Topic
Biomarkers
Lecture Time
13:00 - 13:00
Speakers
  • J. Zhang
Authors
  • J. Zhang
  • X. Wang
  • H. Ying
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

Inflammation and nutrition are two main causes contributing to progression of gastric cancer (GC), and inflammatory biomarker may be presented as its valuable prognostic factor. Thus, this study was carried out to investigate the prognostic significance of preoperative circulating albumin/fibrinogen ratio (AFR), fibrinogen/pre-Albumin ratio (FPR), fibrinogen (Fib), albumin (Alb) and pre-Albumin (pAlb) in surgical GC.

Methods

Materials and Methods: Three hundred and sixty surgical stage II and III GC patients from June 2011 to December 2013 were enrolled in this retrospective study. X-tile software, Kaplan-Meier curve and Cox regression model were used to evaluate the prognostic role of them. A predictive nomogram was established to predict prognosis of overall survival (OS), and its accuracy was assessed by concordance index (c-index).

Results

Decreased Alb (adjusted HR = 1.614, 95%CI=1.103-2.361), pAlb (adjusted HR = 2.111, 95%CI=1.437-3.100), AFR (adjusted HR = 1.540, 95%CI=1.013-2.343) and elevated FPR (adjusted HR = 2.325, 95%CI=1.372-3.940) were significantly associated with shorter OS. FPR was identified as the most effective prognostic factor to predict 3-year’s OS by identified as the most effective prognostic factor to predict 3-year’s OS by time-dependent ROC analysis. A long survival was observed in stage II (P = 0.007) and III (P = 0.002) GC patients with low level of FPR comparing to the patients with high FPR, and the prognosis of III stage FPR-low GC patients undergoing adjuvant chemotherapy was significantly superior to the patients without the treatment (P = 0.002). However, no difference of survival was examined in II stage subgroups stratified by FPR and high FRP of III stage patients with or not the treatment of adjuvant chemotherapy. C-index of nomogram containing FPR (c-index=0.756) was high in comparison with the nomogram without FPR (c-index =0.748).

Conclusions

Preoperative FPR might be a feasible prognostic biomarker in surgical stage II and III GC patients and it could precisely distinguish stage III patients who appeared to benefit from adjuvant chemotherapy. Meanwhile established nomogram based on clinical parameters and FPR could improve its predictive efficacy in 3 years’ OS.

Legal entity responsible for the study

The study was approved by the Ethical Committee of the Second Affiliated Hospital of Nanchang University.

Funding

None

Disclosure

All authors have declared no conflicts of interest.

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53P - Predictive factors for detectability of genomic alterations from circulating cell-free DNA in patients with advanced non-small cell lung cancer (ID 1726)

Presentation Number
53P
Presentation Topic
Biomarkers
Lecture Time
13:00 - 13:00
Speakers
  • H. Kimura
Authors
  • H. Kimura
  • H. Koba
  • K. Kasahara
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

Analysis of circulating cell-free DNA (cfDNA) in patients with malignant tumors is essential for clinical applications. Particularly in the field of lung cancer, examination of oncogene mutations in cfDNA is used in the clinic. However, it is unclear what kind of genomic alterations in DNA derived from tumor cells can be detected in cfDNA. The aim of this study was to analyze the characteristics of detectable genomic alterations in cfDNA.

Methods

Primary lesions, metastatic lesions, and plasma samples from six patients with primary lung cancer who underwent pathological autopsy were analyzed. CfDNA was extracted from 2 mL plasma collected less than 1 month before the patient’s death using a QIAamp Circulating Nucleic Acid Kit (Qiagen), according to the manufacturer’s instructions. Cancer-related target sequencing using a next-generation sequencer for somatic mutation analysis was performed with a Human Comprehensive Cancer Panel (Qiagen). Each tumor sample variant was analyzed in cloud analysis by Qiagen.

Results

The results from one case were analyzed as follows. The numbers of highly confident and meaningful alterations were 1442 for lung tumors, 438 for adrenal glands, 46 for pelvic tumors, and 56 for cfDNA. We compared alterations detected in both DNA extracted from tumor samples and cfDNA and those detected in only DNA extracted from tumor samples.

Conclusions

The findings revealed that the former alterations had higher variant frequencies in DNA extracted from tumor samples than the latter alterations. We will present the data integrated from all six cases.

Legal entity responsible for the study

Kazuo Kasahara, Prof.

Funding

None

Disclosure

All authors have declared no conflicts of interest.

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54P - Cripto-1 expression and its correlation with outcomes in oropharyngeal carcinoma treated by chemoradiation (ID 1914)

Presentation Number
54P
Presentation Topic
Biomarkers
Lecture Time
13:00 - 13:00
Speakers
  • M. Kumar
Authors
  • M. Kumar
  • S. Ghoshal
  • A. Pal
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

Oropharyngeal cancer (OSCC) is one of the leading cancers in incidence and mortality in India. Early detection and treatment of OSCC cancers is needed as most of them present in advanced stages especially in developing countries like India, which may decrease morbidity and mortality. We evaluated the clinical role of CR-1 in patients of squamous cell carcinoma of oropharynx. We present an updated data on outcomes and their association with serum CR-1 levels with a median follow up of two years.

Methods

Fifty healthy volunteers(controls) and fifty biopsy proven cases of OSCC were recruited in the study after using inclusion and exclusion criteria. All patients were treated with radical chemo-radiation and response was assessed at 6 weeks post therapy and from then every 3 months till last follow up. Serum CR-1 levels were analyzed by ELISA in patients, both before and after treatment, and also in controls. Expression of CR-1 was compared between controls and patients. Pre- and post-treatment CR-1 levels in patients were compared and correlated with clinic-pathological findings. SPSSv16.0 was used for statistical analysis.

Results

Complete response (CR) was observed in 42% of the patients, partial response (PR)/stable disease (SD) in 22%, while 26% of the patients had progressive disease (PD) Though the median fall of serum CR-1 levels after treatment was higher in patients who achieved CR compared to those who had PR/SD/PD, the correlation was not significant on multivariate analysis (p = 0.18). CR-1 levels are significantly raised in patients (207 pg/ml Vs 497 pg/ml, p=.003) and are significantly higher in patients with well differentiated and early stage tumors as compared to controls and decreased significantly after treatment at first follow up (497 pg/ml Vs 228 pg/ml, p=.046).

Conclusions

Though the median fall in CR-1 level is higher in patients with CR, a statistically significant correlation could not be established in our study, between median fall of CR-1 levels and long-term outcomes in OSCC but merits larger prospective studies. CR-1 may be useful in early diagnosis of OSCC and as a potential tumor marker.

Legal entity responsible for the study

PGIMER, Chandigarh, India

Funding

None

Disclosure

All authors have declared no conflicts of interest.

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55P - Screening the serum differential protein to predict chemoradiotherapy Efficacy of Xinjiang Uygur Patients with locally advanced Esophageal cancer (ID 1045)

Presentation Number
55P
Presentation Topic
Biomarkers
Lecture Time
13:00 - 13:00
Speakers
  • M. Yang
Authors
  • M. Yang
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00
Biomarkers Poster lunch Poster Display session

56P - Association between HER2 oncoprotein and hormonal receptors (estrogen receptor and progesterone receptor) on breast cancer (ID 1918)

Presentation Number
56P
Presentation Topic
Biomarkers
Lecture Time
13:00 - 13:00
Speakers
  • F. Fulkiadli
Authors
  • F. Fulkiadli
  • D. Khambri
  • W. Harahap
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

The expression of human epidermal growth factor receptors 2 (HER2) and hormonal receptors (estrogen receptor and progesterone receptors) on breast cancer are important markers that always be determined on breast cancer patients. Association between HER2 and hormonal receptors (ER and PR) expression are used as a prognostic and predictive factor on breast cancer. This research aimed to determine the association between HER2, ER, and PR on breast cancer.

Methods

This study was an analytical with cross-sectional design. This study was conducted from May 2015 – December 2015 in oncology division of surgery department RSUP DR. M. Djamil, Padang. Research subjects were 373 of breast cancer patients from 2011 – 2015. Chi square analysis test was used to determine the significant relationship between the variables.

Results

This study involved 124 cases with HER2+ and 249 cases with HER2-. Significant differences in the cases were ER+/HER2- (85.2%) compared with ER+/HER2 (14.8%) with p < 0.001. We also obtained the same tendency on PR+/HER2- (82.7%) compared with PR+/HER2 + (17.3%) with p < 0.001.

Conclusions

This study concluded that there were significant differences between expression of HER2 and hormonal receptors (ER and PR).

Clinical trial identification

This is not a trial idetification research

Legal entity responsible for the study

Medical Faculty of Andalas University

Funding

None

Disclosure

All authors have declared no conflicts of interest.

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58P - Evaluation of awareness, cosmetic and psychological satisfaction following breast oncoplasty among breast cancer patients (ID 1056)

Presentation Number
58P
Presentation Topic
Breast cancer, early
Lecture Time
13:00 - 13:00
Speakers
  • S. Gupta
Authors
  • S. Gupta
  • V. Seenu
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

Breast cancer is the most common cancer amongst women worldwide. Mastectomy leads to a perceived loss of attractiveness and psycho sexual problems. Over the years, increased awareness, improved screening and better therapies have resulted in a considerable decline in mortality, hence women live longer with the physical and psychological trauma of mastectomy. Breast reconstruction is an integral part of breast cancer treatment. However, this is not the case in India where survival itself take precedence over quality of life.

Methods

A prospective cohort study was designed including all outpatients and inpatients, over 18 years of age, diagnosed with breast cancer who consented to participate in the study.

Results

A total of 485 patients were interviewed during the study with a mean age of 47 years, ranging from 18 to 82 years. Amongst these, 26%(126) were illiterate, 55% (266) received minimum secondary level education, only 42 (9%) were working. Majority, 42% (202) of our patients belonged to lower and upper lower socioeconomic status. We found that 15% (71) of our patients were aware about available breast reconstruction options. The most common source of information was the internet. Awareness regarding breast reconstruction was influenced positively by the education status, socio-economic status and profession of the patient (p < 0.01) After thorough counselling, the patients were asked if they would like to opt for reconstruction. A remarkable 49% (239) gave a positive response. A total of 45 breast reconstructions were performed with mean follow up of 15 months. Cosmetic outcome was assessed based on six variables (shape with/without brassiere, symmetry, mobility, consistency, appearance of infra mammary fold). 63% of the patients rated the cosmetic result as excellent. Majority, 68.6% (24), were extremely satisfied with their reconstruction and 51.4% (18) felt a huge positive change in their social life after reconstruction.

Conclusions

Breast oncoplasty awareness is poor in India and is affected by literacy, marriage, professional and socioeconomic status. If made aware, patients tend to opt in for breast reconstruction. In skilled hands, this has excellent cosmetic and psychological satisfaction outcome.

Legal entity responsible for the study

Department of Surgical Disciplines, All India Institute of Medical Sciences, New Delhi, India

Funding

None

Disclosure

All authors have declared no conflicts of interest.

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59P - Development and validation of a nomogram for predicting survival in patients with operable triple negative breast cancer (ID 1172)

Presentation Number
59P
Presentation Topic
Breast cancer, early
Lecture Time
13:00 - 13:00
Speakers
  • J. Liu
Authors
  • J. Liu
  • Y. Yang
  • H. Deng
  • C. Tan
  • W. Wei
  • E. Zhou
  • Q. Liu
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

Personalized nomograms for predicting survival outcomes of operable triple negative breast cancer (TNBC) are scarce. The aim of this study is to develop and validate an effective nomogram to predict disease-free and overall survival for women with early TNBC in China.

Methods

The nomogram was based on a retrospectively analysis on 296 invasive operable TNBC women treated at Sun Yat-sen Memorial Hospital from 2002 to 2014. The predictive accuracy and discriminative ability of nomogram were determined by concordance index (C-index) and calibration curve and compared with the seventh American Joint Committee on Cancer (AJCC) staging system. The model was subjected to bootstrap internal validation and to external validation with a separate cohort of 108 patients from the second Xiangya Hospital and Peking University Shenzhen Hospital.

Results

On multivariate analysis of the training cohort, independent factors for outcomes were stromal tumor-infiltrating lymphocytes (TILs), tumor size, node status, and Ki67 index, which were selected into the nomogram. The calibration curves for probability of disease-free survival (DFS) and overall survival (OS) showed optimal agreement between nomogram prediction and actual observation. The C-index of the nomogram was higher than that of the seventh AJCC staging system for predicting DFS (training cohort: 0.730 vs 0.668, respectively, P = 0.026; validation cohort: 0.750 vs 0.676, respectively, P = 0.051) and OS (training cohort: 0.745 vs 0.676, respectively, P = 0.049; validation cohort: 0.810 vs 0.659, respectively, P = 0.278). The stratification into different risk groups allowed significant distinction between survival curves within respective TNM categories.

Conclusions

We developed a novel well-calibrated nomogram that can provide individual prediction of DFS and OS for operable TNBC based on Chinese breast cancer data. This practical prognostic model can help clinicians in decision making and surveillance recommendation.

Legal entity responsible for the study

Jieqiong Liu

Funding

The National Natural Science Foundation of China

Disclosure

All authors have declared no conflicts of interest.

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60P - Incidence of hypothyroidism in patients treated for carcinoma breast with incidental radiation dose to thyroid gland treated with different fractionation and correlation of these doses with thyroid function test (ID 1305)

Presentation Number
60P
Presentation Topic
Breast cancer, early
Lecture Time
13:00 - 13:00
Speakers
  • N. Sarkar
Authors
  • N. Sarkar
  • H. Govardhan
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

Hypothyroidism is common following radiotherapy in patients with head & neck tumors. The association between radiotherapy and hypothyroidism in breast cancer patients has been investigated in only few studies. On the other hand, radiation exposure to parts of the thyroid gland seems unavoidable in breast cancer patients receiving radiotherapy to the ipsilateral supraclavicular fossa. Studies reveal that hypothyroidism is related to volume of thyroid gland and dose received. This study is taken up to find such correlation between volume of thyroid and thyroid function test.

Methods

A total of 83 patients treated with adjuvant radiation therapy in carcinoma breast were included. All patients were treated with 3DCRT. V20, V30, V40 and V50 calculated for all patients using standard DVH. Base line thyroid function test and clinical assessment was done before radiation therapy. All patients were treated with 50Gy in 25 fractions (Conventional arm) or 40Gy in 15 fractions (Hypo fractionated arm) to chest wall and SCF. After therapy, TFT and clinical evaluation were done at every 3 months interval for a year.

Results

Mean thyroid volume was found to be 10.3cc. Mean dose received by thyroid gland was 47.5Gy in Conventional arm and 38Gy in Hypo fractionated arm. The V20, V30, V40 and V50 of thyroid gland in the Conventional arm were 60.6, 56.5, 53.3 and 35.2%. Mean TSH change between baseline and 1 year was 40.9% in Conventional arm and 35.2% in Hypo fractionated arm.

n = 83Subclinical hypothyroidismClinical hypothyroidismTotal
Baseline (0 month)011
6TH month6612
Conventional arm (n = 43)538
Hypofractionated arm (n = 40)134
1 Year6915
Conventional arm (n = 43)459
hypofractionated Arm (n = 40)246

No significant correlation was observed with radiation dose to thyroid gland and thyroid function test. A significant correlation was noted with TSH level and thyroid volume in the 50Gy arm. Thyroid volume <10cc was found to be statistically significant to develop both subclinical and clinical hypothyroidism.

Conclusions

In our study we did not find any significant correlation between thyroid radiation doses with the changes in TFT parameter. Patients who received conventional fractionation and with thyroid volume <10cc were affected more with hypothyroidism after radiation therapy.

Legal entity responsible for the study

SELF

Funding

None

Disclosure

All authors have declared no conflicts of interest.

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61P - No change in mean age of diagnosis of breast cancer during 30 years from 1981 to 2011 in the north east of Iran, report of six thousand patients (ID 1383)

Presentation Number
61P
Presentation Topic
Breast cancer, early
Lecture Time
13:00 - 13:00
Speakers
  • M. Salehi
Authors
  • M. Salehi
  • S. Shahidsales
  • M. Seilaniantousi
  • G. Noferesti
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

Patterns of breast cancer differ greatly between Asian and Western countries and this study aimed to evaluate the age at the time of diagnosis of breast cancer and it’s probably changes in distribution among patients during 30 years

Methods

This cross-sectional study was conducted in Mashhad, Iran from 1981 until 2011. The data of 6274 breast cancer patients were obtained from case records. The duration of study was categorized into three periods: 1981-1990, 1991-2000 and 2001-2011. SPSS software was used for analyses.

Results

Mean age at the time of diagnosis was 49.07 ± 12.07 years (male: 56.48 ± 14.14, female: 48.8 ±12.01, p < 0.001). Table presents the mean age of studied patients in each 10 years of study. ANOVA test showed that there was no statistically significant difference (P value= 0.1).

DecadesFrequencyMean ageSDYoungestOldest
1981-199046747.9712.0431888
2000-1991177149.0312.3382099
2001-2011394949.2211.9542098

The most frequent histologic type of breast cancer was ductal carcinoma 65.6% others in order were: NOS 19.6%, lobular 3.7%, medullary 2.8%, adenocarcinoma 2.8%, tubular and papillary 0.2%, and 5.1% of other types. Relative frequency of histologic types had significant differences among 3 intervals (p < 0.001), the frequency of adenocarcinoma was decreasing but ductal carcinoma was increasing during 3 decades. Mean age of ductal carcinoma, lobular, medullary and adenocarcinoma was 48.9±11.8, 50.6±12.4, 46.4±11.4, 50.2±11.9, respectively. Mean age had significant differences among these main histologic types (p = 0.002).98% of patients were urban and 2% were rural. The frequency of people living in urban areas increased significantly (p < 00.1) during these 30 years compared with rural areas.

Conclusions

Breast cancer occurs in Iranian women at least one decade younger than in women in developed countries. We found no change in mean age of diagnosis of breast cancer during these 30 years from 1981 to 2011.

Clinical trial identification

N/A

Legal entity responsible for the study

Mashhad University of Medical Sciences

Funding

Mashhad University of Medical Sciences

Disclosure

All authors have declared no conflicts of interest.

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62P - The pattern of recurrence in initial pure ductal carcinoma-in-situ of the breast: 19 years experience of King Chulalongkorn Memorial Hospital, Thailand (ID 1784)

Presentation Number
62P
Presentation Topic
Breast cancer, early
Lecture Time
13:00 - 13:00
Speakers
  • P. Wanchaijiraboon
Authors
  • P. Wanchaijiraboon
  • T. Atikankul
  • N. Parinyanitikul
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

The rate of recurrence after treatment for pure DCIS has been recognized range from 5-20%. Approximately half of these patients are invasive and less than 1% is distant metastasis. The aims of our study was to identify pattern of recurrence, clinicopathological makers of recurrence in King Chulalongkorn Memorial Hospital.

Methods

One hundred and seventy- four patients who diagnosed with pure DCIS between 1998 and 2016 at King Chulalongkorn Memorial Hospital were reviewed retrospectively. The clinical and pathologic characteristics of DCIS patients including pattern of locoregional recurrence and distant metastasis were analyzed.

Results

In initial analysis, 17 from 174 patients (9.8%) with initially pure DCIS were diagnosed with recurrent disease. 15 out of 17 (88.2%) patients were loco-regional recurrence. Distant metastasis was rarely reported in 2 out of 17 patients (11.8%). For recurrent subgroup, the median age was 47.5 years (33-66) and 50% had tumor size more than 1 centimeter. 75% had histologic grade I-II, none of patients had DCIS with comedonecrosis, 92% had DCIS with positive estrogen receptor and 61% had negative margin, but approximately 30% had closed margin. In term of treatment, 58.8% underwent wide excision, 21.1% received postoperative radiation, 28.6% received 5 years tamoxifen for prevention. The median time of overall recurrence was 103 months (11-205). Only one patient had died of disease. Disease free survival and overall survival will be further analyzed.

Conclusions

Pattern of recurrence after diagnosis of pure DCIS is mostly loco-regional recurrence and rarely distant metastasis. Further study of clinicopathological predictors is essential for early prevention and improved the treatment outcome of pure DCIS patients.

Legal entity responsible for the study

Medical Oncology Unit, Internal Medicine Department, King Chulalongkorn Memorial Hospital

Funding

None

Disclosure

All authors have declared no conflicts of interest.

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63P - Early drop of LV ejection fraction can predict trastuzumab-related cardiotoxicity in patients with breast cancer (ID 1932)

Presentation Number
63P
Presentation Topic
Breast cancer, early
Lecture Time
13:00 - 13:00
Speakers
  • J. Cho
Authors
  • J. Cho
  • E. Kim
  • K. Yoo
  • H. Lee
  • H. Kim
  • M. Heo
  • J. Park
  • J. Ahn
  • Y. Im
  • Y. Park
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

While concerns about trastuzumab-related cardiac dysfunction (TRCD) in patients with breast cancer (BRCA) increasing, there is a lack of evidences to support current recommendation to monitor TRCD. Especially, in Asian population, clinical manifestations and predictors of TRCD were unknown. Therefore, we aimed to identify characteristics and predictors of TRCD in Asian patients with BRCA.

Methods

From 2003 to 2016, consecutive 1371 patients who treated with adjuvant trastuzumab for BRCA were enrolled. We excluded patients with metastatic BRCA, number of trastuzumab administration <3 times, or without serial echocardiographic data. TRCD was defined as decrease > 10% in left ventricular ejection fraction (LVEF), with a decline below the normal limit value (50%). Median follow-up duration was 54.2 months.

Results

Of 787 patients evaluated (mean age, 50.3±9.5 years), 58 (7.4%) were developed TRCD (median time to develop TRCD, 6.1 [3.1-7.9] months) and most of them (75.9%) were improved from TRCD after 5.7 (3.5-17.7) months. TRCD patients had higher baseline blood pressure (SBP, mmHg; 125 [107-136] vs 114 [104-126], p = 0.005 and DBP, mmHg; 72 [65-81] vs 68 [61-76], p = 0.004), lower initial LVEF (63 [59-66] % vs 65 [61-68] %, p = 0.016) and more frequently administered anthracycline (98% vs 89%, p = 0.022). Cumulative dose of anthracycline was also higher in those with TRCD (404 [374-458] mg vs 372 [336-400] mg, p < 0.001). There were no differences in concurrent radiotherapy, cancer location/stage and previous history of cardiovascular disease between two groups. On follow-up echocardiography, EF drop >5% within 3 months regardless of absolute LVEF value was more frequent in TRCD patients (78.3% vs 38.4%, p < 0.001). In multivariate analysis, EF drop>5% within 3 months from trastuzumab administration was significantly associated with development of TRCD (HR, 45.1[17.0-127.6], p < 0.001) as well as baseline LVEF and cumulative dose of anthracycline.

Conclusions

Asian BRCA patients received adjuvant trastuzumab were relatively young and less frequently developed TRCD compared to Western data. LVEF drop >5% within 3 months from trastuzumab administration was a strong predictor of TRCD.

Legal entity responsible for the study

Yeon Hee Park

Funding

None

Disclosure

All authors have declared no conflicts of interest.

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64P - Prediction of survival after neoadjuvant chemotherapy for breast cancer by evaluation of tumor-infiltrating lymphocytes within fibrotic foci of tumor stroma (FF-TILs) (ID 1364)

Presentation Number
64P
Presentation Topic
Breast cancer, early
Lecture Time
13:00 - 13:00
Speakers
  • S. Kashiwagi
Authors
  • S. Kashiwagi
  • Y. Asano
  • W. Goto
  • K. Takada
  • T. Takashima
  • T. Morisaki
  • S. Noda
  • N. Onoda
  • K. Hirakawa
  • M. Ohira
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

Monitoring the host immune response to tumors in the cancer microenvironment helps predict treatment response and outcome. Tumor-infiltrating lymphocytes (TILs), which are indicators for monitoring an immune response, are generally mononuclear immunocytes that aggregate with tumors and are thought to have a close relationship with cancer cells. On the other hand, a fibrotic focus (FF) within the stroma of a tumor is a histological formation that plays an important role in the cancer microenvironment with regard to proliferation and development. Here, we focus on TILs that exist within the FF and we have performed pathological evaluations. Among patients undergoing neoadjuvant chemotherapy (NAC) for breast cancer, we evaluated the prediction of treatment effects using FF-TILs.

Methods

Of the 320 patients were treated with NAC, 239 subjects who were able to evaluate FF-TILs were targeted. The FF is a converged focus of the tissue component of the stroma of a tumor, and it is surrounded by infiltrating tumor cells. Lymphocytes that infiltrate the FF are FF-TILs.

Results

The disease-free survival (DFS) period after NAC for the high-FF-TIL group was found to be significantly longer than that for the low-FF-TIL group for all cases (p < 0.001, log-rank) and for all subtypes of triple-negative breast cancer (TNBC) (p = 0.001, log-rank), human epidermal growth factor receptor 2-enriched breast cancer (HER2BC) (p = 0.010, log-rank), and hormone receptor-positive breast cancer (HRBC) (p = 0.003, log-rank). In multivariable analysis as well, high-FF-TIL group classification was an independent factor for recurrence after NAC for all cases (p < 0.001, hazard ratio (HR) = 0.198) and all subtypes of TNBC (p = 0.006, HR = 0.172), HER2BC (p = 0.025, HR = 0.135), and HRBC (p = 0.007, HR = 0.228).

Conclusions

It is suggested that FF-TILs are a useful factor for predicting recurrence of breast cancer after NAC.

Legal entity responsible for the study

Shinichiro Kashiwagi

Funding

None

Disclosure

All authors have declared no conflicts of interest.

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65P - The possibility of omitting axillary clearance by using indocyanine green fluorescence method in detection of sentinel lymph nodes in early-stage breast cancer (ID 1497)

Presentation Number
65P
Presentation Topic
Breast cancer, early
Lecture Time
13:00 - 13:00
Speakers
  • Y. Maeshima
Authors
  • Y. Maeshima
  • A. Oobayashi
  • R. Katsuragi
  • Y. Yoshimoto
  • S. Takahara
  • A. Yamauchi
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

The AMAROS trial and the ACOSOG Z0011 trial showed that axillary lymph node dissection (ALND) could be spared in certain breast cancer patients with sentinel lymph node (SLN) metastasis on condition with treatment by axillary radiotherapy and adjuvant systemic therapy. Sugie et al. reported that the indocyanine green (ICG) fluorescence method had a high SLN identification rate and a high number of SLNs. They founded that positive SLN was usually identified within the first 4 resected SLNs, which could safely replace axillary clearance for surgeons otherwise willing to perform further axillary treatment. However, the data of long-time observation of the ICG fluorescence method was few. We report the axillary recurrence rate and the rate of lymphedema after SLN biopsy using ICG fluorescence method to investigate to the possibility of sparing an ALND without residual positive nodes in axilla.

Methods

From May 2011 to December 2015, a total of 500 patients (511 axillas) with clinically node-negative breast cancer were received SLN biopsy using combination with ICG fluorescence and radioisotope, and we analyzed 493 axilla.

Results

The median number of resected SLNs was 4.27, and median number of positive SLN nodes was 0.23. Median follow-up duration was 41 months, and axillary recurrence occurred in 5 of 493 axillas (1.01%). Four patients in the SLN positive group were not conducted the standard adjuvant therapy because of patient’s preference. Seventy-eight patients had positive SLNs, and median number of positive SLNs in 78 patients was 2.39. Although ALND was omitted for all patients, the axillary recurrence was 2 of 78 patients (2.56%), all of whom adjuvant therapy were insufficient. Lymphedema after SLN biopsy occurred in 6 patients (1.2%), but all of them had low grade.

Conclusions

Our data indicate that by SLN biopsy using ICG fluorescence method, the axially recurrence rate is low when treated with appropriate adjuvant therapy. Because positive SLN was usually identified within the first 4 resected SLNs, the axillary recurrence rate was low by resecting 4 SLNs, which suggests the possibility of omitting ALND without lymphedema.

Legal entity responsible for the study

Akira Yamauchi

Funding

None

Disclosure

All authors have declared no conflicts of interest.

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66P - Prognostic and clinical values for prediction of breast cancer recurrence in HER2 positive early breast cancer after surgery in King Chulalongkorn Memorial Hospital 2005-2016 (ID 1654)

Presentation Number
66P
Presentation Topic
Breast cancer, early
Lecture Time
13:00 - 13:00
Speakers
  • S. Prapatsornvichit
Authors
  • S. Prapatsornvichit
  • N. Parinyanitikul
  • T. Atikankul
  • S. Virote
  • N. Poovorawan
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

Human epidermal growth factor receptor 2 (HER-2) overexpressed breast cancer occurs in 15-20% and associated with diminished disease-free and overall survival. After surgery, the standard treatment in HER-2 positive early breast cancer is systemic chemotherapy combined with trastuzumab. However, one fifth of these patients had disease recurrence in five years after treatment. So, the study was aimed to identify prognostic and clinical values that associated with survival outcomes especially in term of recurrence free survival.

Methods

One hundred and sixty-nine patients with early stage HER-2 positive breast cancer who were diagnosed and treated at King Chulalongkorn Memorial Hospital from January 2005 to December 2016 were reviewed retrospectively. Clinico-pathologic features and survival outcomes were analyzed.

Results

In initial analysis, median age was 50 years (26-83), 49.1% had premenopausal status, 93.4% had invasive ductal carcinoma, 52.6% had T2 tumor, 58.6% had node negative, 46.1% had lymphovascular invasion, 79.2% had free margin and 46.7% had positive estrogen and progesterone receptor. For the treatment, 69.8% underwent modified radical mastectomy, 96.4% received neoadjuvant/adjuvant chemotherapy, 55.6% received adjuvant trastuzumab, 48.5% received adjuvant hormonal therapy and 68% received post-operative radiotherapy. 35 out of 169 (20.7%) patients had recurrence disease. Distant metastasis was identified in 62.8%. From univariate and multivariate analysis, trastuzumab used (HR 0.44 [95%CI 0.21-0.9]; p = 0.007 from multivariate) and surgical margin (HR 1.02 [95%CI 1.0-1.03]; p = 0.012 from multivariate) were associated with increase risk of recurrences. After median follow up 4.9 years, the 5-years recurrence free survival was 81.2%, 89.2% and 70.7% in overall populations, trastuzumab used subgroup and non-trastuzumab used subgroup, respectively. Overall survival will be further analyzed.

Conclusions

Trastuzumab used and surgical margin status were statistically significant prognostic values for predicting disease recurrence in HER-2 positive early breast cancer.

Legal entity responsible for the study

Division of Medical Oncology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and the King Chulalongkorn Memorial Hospital.

Funding

None

Disclosure

All authors have declared no conflicts of interest.

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67P - Prediction model of low risk recurrence distinguished by 21-gene recurrence score in hormone receptor-positive invasive breast cancer: A validation study (ID 921)

Presentation Number
67P
Presentation Topic
Breast cancer, early
Lecture Time
13:00 - 13:00
Speakers
  • Y. Tsuchida
Authors
  • Y. Tsuchida
  • N. Hayashi
  • F. Omata
  • S. Ohde
  • Y. Kanada
  • S. Tazawa
  • M. Takimoto
  • K. Suzuki
  • S. Nakamura
  • H. Yamauchi
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

The 21-gene Recurrence Score (RS) (Oncotype DX®; Genomic Health, Redwood City, CA) is the most valid and reliable multigene assay to predict prognosis or response to chemotherapy in hormone receptor-positive invasive breast cancer patients. In Japan, however, the test is not frequently used because of its expensive and no coverage by national insurance. We have developed a model to predict low recurrence risk (low-RS) using 220 patient data from St. Luke’s International Hospital, Tokyo, Japan (presented at San Antonio Breast Cancer Symposium 2016). The model with 4 factors, including the histologic type (invasive ductal or lobular), the expression level of PgR (Allred score 7,8 or < 6) and Ki67 (< 24 or > 24), and the presence of lymphovascular invasion, showed that 92% of patients with high PgR positive and Ki67 < 24 could be classified as low-RS with an AUC of 0.843 (95%CI: 0.790-0.896). The aim of this study was to validate our prediction model with external patient data.

Methods

A validation set of clinicopathological data from 77 patients who had primary invasive carcinoma surgically resected and underwent OncotypeDx® was obtained from Showa University, school of medicine, Tokyo, Japan.

Results

According to the distribution of 4 factors between two cohorts, there was a significant difference in Ki67 level (<0.01) but not in histologic type, the expression level of PgR, and lymphovascular invasion. The prediction model of the validation cohort had still high enough discriminatory ability having an AUC of 0.705 (95%CI: 0.584-0.827).

Conclusions

Regardless of the inconsistency of Ki67 level between institutes, our model could provide useful information to predict low-RS in hormone receptor-positive invasive breast cancer patients. This model would be helpful to select patients who had better apply OncotypeDX®.

Legal entity responsible for the study

Yasue Tsuchida

Funding

None

Disclosure

All authors have declared no conflicts of interest.

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68P - Breast cancer epidemiology: Worldwide data (ID 1286)

Presentation Number
68P
Presentation Topic
Breast cancer, early
Lecture Time
13:00 - 13:00
Speakers
  • P. Bagri
Authors
  • P. Bagri
  • S. Narayan
  • P. Pareek
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00
Breast cancer, early Poster lunch Poster Display session

69P - Prognostic significance of biomarker discordance in breast cancer patients with neoadjuvant chemotherapy (ID 1769)

Presentation Number
69P
Presentation Topic
Breast cancer, early
Lecture Time
13:00 - 13:00
Speakers
  • A. Matsumoto
Authors
  • A. Matsumoto
  • M. Yoshikawa
  • H. Jinno
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

Neoadjuvant chemotherapy (NAC) was reported to change the status of biomarker including estrogen receptor (ER), progesterone receptor (PgR), HER2 and Ki67. However, the impact of these changes on clinical outcome still remains to be elucidated. The objective of this study is to evaluate the biomarker discordance of breast cancer patients treated with NAC and its prognostic impact.

Methods

From a prospective database of 243 patients receiving NAC from January 2005 to November 2016, 183 patients (75.3%) with non-pCR were analyzed. ER, PgR, HER2 and Ki67 status were assessed in core needle biopsy performed prior to NAC and surgical specimens. Ki67 status was classified as high (> 20%) and low (< 20%) level.

Results

The median age was 56.0 (range: 29–79) years and the mean tumor size was 3.38 ± 2.19 cm. Clinical nodal status was positive in 59.0% of patients before NAC. ER, PgR and HER2 were positive in 71.6%, 58.5% and 29.4% of patients before NAC. Discordance in ER, PgR and HER2 status between before and after NAC were 9.3% (4.9% gain; 4.4% loss), 18.6% (6.6% gain; 12.0% loss) and 10.0% (2.8% gain; 7.2% loss), respectively. The rate of HER2 loss was significantly higher in patients treated with trastuzumab, when compared with patients without trastuzumab (31.7% vs. 0%, P = 0.028). Patients with a loss in ER status after NAC tended towards a worse disease-free survival (DFS) compared with patients who maintained the ER positivity (14.7 vs. 37.9 months, P = 0.196). Conversely, a loss in PgR status did not correlate with worse DFS (42.3 vs.42.5 months, P = 0.495). The median Ki67 status was significantly decreased after NAC (25.0% vs. 4.5%; P < 0.001). Among patients with high Ki67 status before NAC, clinical response rate was significantly higher in the group with decreased Ki67 status to low level after NAC, when compared with the group which maintained high Ki67 status (93.9% vs. 50.0%, P = 0.001). Patients with concordant-high Ki67 status had a significantly worse DFS compared with patients with concordant-low Ki67 status (8.7 vs. 22.5 months; P = 0.011).

Conclusions

These data suggested that biomarker status on residual disease after NAC might be helpful in selecting patients at different risk of relapse.

Legal entity responsible for the study

Teikyo University School of Medicine

Funding

None

Disclosure

All authors have declared no conflicts of interest.

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70P - Outcomes of sentinel lymph node biopsy after neoadjuvant chemotherapy (ID 1975)

Presentation Number
70P
Presentation Topic
Breast cancer, early
Lecture Time
13:00 - 13:00
Speakers
  • S. Rashad
Authors
  • A. Bulbul
  • S. Rashad
  • E. Mino
  • A. Bautista
  • A. Mustafa
  • S. Chouial
  • M. Khorsand
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

Axillary sentinel lymph node biopsy (SLNB) is a single lymph node or first set of nodes that receive direct lymphatic drainage from a primary tumor. The number of nodes examined, minimal surgeon experience may increase false negative rates (FNR), the results reported in the literature are however inconsistent. The adequate number of SLN required for achieving a low FNR remains controversial especially those receiving neoadjuvant chemotherapy (NAC).

Methods

We retrospectively evaluated 539 patients between Jan 1989 – Oct 2015, Median age 64 (30 – 91) with a median follow-up of 8.9 (0.03, 26.8) years. SLNB was performed post NAC in 210 clinically N0 breast cancers by community breast surgeons across three rural surgical practices. Logistical regression analysis was used to assess the relationship of recurrence with SLNB using SAS ver.9.3. FNR was calculated by evaluating 70/210 patients who received AD (Axillary dissection) post SLNB and were found to have positive nodes on AD. Technique used for SLNB was recorded.

Results

Six patients had positive nodes on AD despite a negative SLNB yielding an overall FNR of 8.5% (6/70) post NAC. All FN patients had ≤ 2 SLNs removed, they were in Isosulfan blue dye (IBD) group and had a Ki67>10%. The number of SLNs identified ranged from 1 to 9 (mean, 2.2; median 2). FNR for 2 or more SLNs removed was 2.8% (2/70), above 3 SLNs FNR was 0%. Three patients had SLNB failure (no nodes detected). (IBD) was used in 83/198 (42%), technetium sulfur colloid (TSC) in 101/198 (51%) both 12/198 (6%). Among patient with SLNB, the local recurrence was 5.34%. No adjuvant radiation increased the likelihood of LR by 2.92-fold. LR rates were similar with IBD or TSC (p = 0.79).

Conclusions

FNR of 2.8% or lower can be achieved with surgeons in rural practices with limited volumes if ≥ 2 SLN are removed. LR rates were consistent with Z-0011. Surgeons in our study preferred mostly blue dye due to cost issues and does not affect LR. Excisional biopsies tend to be common in rural practices although not recorded in our study may also have a role to play since disruption may alter the lymphatic flow leading to FNR. We hypothesize that there might be an optimal threshold number of SLNs removed to achieve acceptable FNR 0-5% if 2-3 SLNs are removed. NAC had acceptable overall FNR of 8.5%.

Legal entity responsible for the study

Kymera Independent Physicians

Funding

None

Disclosure

All authors have declared no conflicts of interest.

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71P - Is sentinel lymph node biopsy necessary in breast cancer patients who were diagnosed as initially clinically node-negative before neoadjuvant chemotherapy? (ID 2036)

Presentation Number
71P
Presentation Topic
Breast cancer, early
Lecture Time
13:00 - 13:00
Speakers
  • T. Fujita
Authors
  • T. Fujita
  • M. Sakuragi
  • C. Miyazaki
  • S. Siba
  • Y. Tanaka
  • R. Koike
  • M. Shiozawa
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

Neoadjuvant chemotherapy (NAC) is established for treatment of locally advanced disease and is being used increasingly for early-stage breast cancer. And sentinel lymph node biopsy (SLNB) for clinically node-negative (cN0) breast cancer patients after NAC is performed as a daily procedure. The purpose of this study was to identify the group that can omit SLNB in patients with cN0 breast cancer at diagnosis before NAC.

Methods

A retrospective analysis was performed of 69 patients who were diagnosed as cN0 before NAC and underwent SLNB between 2005 and 2016. Before NAC, all patients underwent clinical assessment of lymph node status by ultrasound. We judged patients to be node-negative when ultrasound showed no suspicious nodes, and if axillar lymph nodes were swelling, fine needle aspiration cytology was performed. 62 patients received anthracycline-based chemotherapy and 6 patients received taxane alone. SLNB procedure and partial resection was done after NAC in all patients. Lymphatic mapping was performed with radioactive colloid and lymphatic blue dye.

Results

Median follow-up time was 48 months. Success rate for the identification and removal of SLNs was 94.2% (65/69). The median number of SLNs removed was 2. In breast cancer patients who were diagnosed as cN0 before NAC, only 5 patients (7.2%) represented SLN involvement and were performed axillar dissection. And the SLNs were the only positive nodes in 3 patients. No SLN metastases were observed in 11 patients who were diagnosed as clinical complete response (cCR) by ultrasound and MRI. But 5 patients (9.3%) had positive SLN in the 54 patients who were diagnosed as clinical partial response or clinical stable disease (p = 0.38). Tumor size, hormone receptor status and HER2 status did not influence the positive rate of SLN metastases. No axillar lymph node recurrence was observed within follow-up period.

Conclusions

Our results show that SLNB is necessary even in breast cancer patients who were diagnosed as cN0 before NAC. But SLNB may be omitted in breast cancer patients who were diagnosed as cN0 before NAC and as cCR by ultrasound and MRI after NAC.

Legal entity responsible for the study

Jichi Medical University

Funding

None

Disclosure

All authors have declared no conflicts of interest.

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72P - Prognostic significance of tumor-infiltrating lymphocytes (TILs) in patients with early-stage triple-negative breast cancer (TNBC) treated with curative resection alone (ID 2099)

Presentation Number
72P
Presentation Topic
Breast cancer, early
Lecture Time
13:00 - 13:00
Speakers
  • J. Park
Authors
  • J. Park
  • H. Lee
  • J. Ahn
  • J. Kim
  • K. Jung
  • G. Gong
  • S. Kim
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

Tumor infiltrating lymphocytes (TILs) has been highlighted as a reliable prognostic and predictive biomarker in patients with triple negative breast cancer (TNBC). However, there has been lack of data investigating its significance in curatively resected, early-stage TNBC without adjuvant chemotherapy.

Methods

We retrospectively collected patients with TNBC regardless of the stage and histologic subtype, who underwent curative resection alone without adjuvant chemotherapy between 1999 to 2012 at Asan Medical Center (Seoul, Korea). In addition, we explored the clinical impact of TILs in subset of pathologically node-negative or small primary (≤1.0cm) tumors.

Results

In a total of 78 patients, 71.8% were pathologically stage I, but nodal involvements were found in 12.8%. The reasons of no adjuvant chemotherapy were mostly patients’ refusal (73.1%) followed by physician’s discretion. All patients were available with TILs in surgical specimens with their median value of 26% (range, 1 to 90). During the median follow-up period of 74 months (range, 67 to 81), 21 patients (26.9%) experienced relapse, and 8 (10.3%) died of breast cancer progression. In relapsed patients, local relapse only was found in 14 patients (17.9%), whereas 7 (9.0%) accompanied distant metastases. Interestingly, TILs≤10% was significantly associated with distant metastasis at relapse (p = 0.050). Relapse with distant metastasis, pathological nodal positivity, and lower TILs were significantly correlated with inferior DSS (p < 0.001, p = 0.053, and p = 0.012). In node-negative TNBC, the only factor significantly associated with inferior DSS was TILs≤10% (p = 0.055). In 30 patients (38.5%) with small primary and node-negative TNBC, 3 relapses (10.0%) were observed including 2 cases of tumor size smaller than 0.6cm, and TILs≤10% showed relevant correlations with inferior RFS and DFS (p = 0.072, p = 0.317 respectively).

Conclusions

TILs might be a potential prognostic marker for early-stage TNBC who treated with curative resection alone, particularly in node negative or small primary TNBC. In these subsets, patients with TILs ≤10% may benefit from adjuvant chemotherapy.

Legal entity responsible for the study

N/A

Funding

None

Disclosure

All authors have declared no conflicts of interest.

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73P - Role of post mastectomy radiotherapy in T1, T2 lesions with 1-3 positive axillary lymph nodes-study of 101 cases (ID 894)

Presentation Number
73P
Presentation Topic
Breast cancer, early
Lecture Time
13:00 - 13:00
Speakers
  • N. Garg
Authors
  • N. Garg
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

Post mastectomy radiotherapy (PMRT) reduces loco-regional recurrence (LRR) and improves overall survival. There is international consensus to recommend PMRT for patients with tumour size more than 5 cm, tumour invasion of the skin, pectoral muscle or chest wall and patients with > 4 positive lymph nodes. However, the role of PMRT for patients with T1, T2 disease with 1–3 positive LN is still controversial. The side effects of radiotherapy and its associated morbidity have to be considered in the risk benefit ratio, thus difficult to arrive at consensus in early breast cancer.

Methods

101 patients treated between 2012 to 2015 were studied retrospectively, The inclusion criteria for this analysis were: (1) Female patients with unilateral breast cancer and no distant metastasis at initial diagnosis who underwent mastectomy and axillary lymph node dissection; (2) postoperative pathology indicated T1–2 and 1–3 positive axillary lymph nodes (T1–2N1M0) disease, at least 10 lymph nodes removed by axillary dissection; (3) complete surgical resection of the tumor and negative margins; (4) complete estrogen receptor (ER), progesterone receptor (PR) and human epithelial growth factor receptor family 2 (Her2) status; (5) No neoadjuvant chemotherapy was administered before surgery and endocrine therapy was performed based on the hormone receptor status. In order to study the research questions, we formulated hypotheses as follows,1. Radiotherapy does not have any impact on recurrence post mastectomy.2. There is no influence of Peri nodal extention on recurrence. The above hypotheses were tested using chi-square test.

Results

Recurrences were obtained in 9 amongst radiotherapy and without radiotherapy in 16. When chi square was applied, the value was highly significant. Hence our hypothesis was rejected. Also in case of PNE with recurrence and radiotherapy, 8 had PNE with radiotherapy and recurrence and 27 had no recurrence, p value was 0.013% hence highly significant.

Conclusions

Radiotherapy should be strongly considered in patients with 1-3 nodes post mastectomy as it decreases the chances of recurrence.

Legal entity responsible for the study

GCRI Ahmedabad, India

Funding

None

Disclosure

All authors have declared no conflicts of interest.

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74P - Febrile neutropenia and primary prophylactics in docetaxel plus cyclophosphamide chemotherapy for breast cancer: A Japanese institution experience (ID 1258)

Presentation Number
74P
Presentation Topic
Breast cancer, early
Lecture Time
13:00 - 13:00
Speakers
  • Y. Kimura
Authors
  • Y. Kimura
  • S. Sasada
  • N. Goda
  • A. Emi
  • K. Kajitani
  • N. Masumoto
  • R. Haruta
  • T. Kadoya
  • T. Kataoka
  • M. Okada
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

Incidence of febrile neutropenia (FN) caused by docetaxel/cyclophosphamide (TC) therapy varies widely from country to country (5% at US Oncology research trial and 68.8% at Japanese trial), and the high hematotoxicity observed in Japanese patients may reduce relative dose intensity (RDI).

Methods

Between April 2009 and June 2017, 205 patients with breast cancer received TC therapy (75/600 mg/m2, every 3 weeks, 4 cycles). We investigated the incidence of FN and RDI of TC therapy and the factors related to FN and low RDI.

Results

The median patient age was 53 years. Fifty-five patients received primary prophylactics (20 granulocyte-colony stimulating factor (G-CSF) and 35 antibiotics). Excluding 9 patients with allergic reaction, FN occurred in 68 patients (34.7%). Among patients with primary prophylactic G-CSF, only one developed FN, whereas FN occurred in all the 11 patients with prophylactic antibiotics. Hospitalization was required in 6.3% of patients. In multivariate analysis, the independent risk factors of FN were older age (≥60 years, p = 0.017) and without primary prophylactic G-CSF (p = 0.011). The median RDIs of docetaxel and cyclophosphamide were 96.7% and 99.7%, respectively. Low RDI (<85%) was related to older age (p < 0.001), but not to primary prophylactics (G-CSF p = 0.247 and antibiotics p = 0.862).

Predictors of FN incidence

FactorsUnivariate analysis
Multivariate analysis
Odds ratio (95% CI)POdds ratio (95% CI)P
Age ≥60y5.16 (2.32-11.50)<0.0012.19 (1.15-4.17)0.017
Hepatic dysfunction1.85 (0.40-8.62)0.4402.39 (0.56-10.10)0.237
Renal dysfunction0.28 (0.06-1.38)0.1200.82 (0.29-2.30)0.708
Prophylactic G-CSF0.39 (0.08-1.92)0.2500.07 (0.01-0.54)0.011
Prophylactic antibiotics1.08 (0.43-2.72)0.8600.59 (0.26-1.34)0.206

Conclusions

Even though the FN incidence of TC therapy was over 20%, low hospitalization rate and high RDI were achieved in Japanese patients. Primary prophylactic G-CSF was useful to reduce FN of TC therapy for breast cancer, especially in older patients.

Legal entity responsible for the study

Hiroshima University

Funding

None

Disclosure

All authors have declared no conflicts of interest.

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75P - Can sentinel lymph node biopsy be omitted in patients with clinical node negative before neoadjuvant chemotherapy (ID 1896)

Presentation Number
75P
Presentation Topic
Breast cancer, early
Lecture Time
13:00 - 13:00
Speakers
  • T. Yoshida
Authors
  • T. Yoshida
  • A. Yoshida
  • N. Hayashi
  • H. Yamauchi
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

Recently minimum axillary surgery has been indicated due to its morbidity. Since the report of Z011, there is a change in axillary management, and even if metastasis is proven in Sentinel node biopsy (SNB), the patients whose axillary dissection is omitted are increasing. If a patient who SNB is unnecessary can be found before surgery, it can be possible to treat the patient more generously. We retrospectively reviewed the patients in which neo adjuvant chemotherapy (NAC) was performed with clinically N0 (cN0) and SNB was performed, and examined clinicopathological factors whether we can find patients who do not need even SNB biopsy.

Methods

A retrospective cohort study of cN0 breast cancer patients before NAC and who underwent breast surgery was conducted, investigating 199 consecutive patients between 2009 and 2015 in our hospital. Institutional review board approved this retrospective study. Between the patients with or without nodal metastasis in SNB after NAC, we compared the differences in clinicopathological factors including Estrogen Receptor (ER), Progesterone Receptor (PgR), human epidermal growth factor receptor 2 (HER2), nuclear grade(NG), Ki-67 in needle biopsy specimens, and tumor size before NAC, and complete response on MRI (MRI-CR) after NAC. We defined MRI-CR as no residual enhancement, or non-invasive faint and indistinct enhancement.

Results

Of the 199 patients, 184 patients (92%) were pathological node negative and 15 patients (8%) are node positive after NAC. In univariate analysis, patients achieved MRI-CR (p < 0.01), with high NG (p = 0.04), without PgR expression (p = 0.04) and high Ki-67 were significantly correlated node negative in SNB. In multivariate analysis, the patients with MRI-CR (p < 0.01, HR 10.716) and high Ki-67 (p < 0.01, HR 7.577) were significantly correlated node negative in SNB. In ER negative and HER2 positive type no lymph node metastasis was found (0/26 patients).

Conclusions

Detection of MRI-CR in patient with cN0 before NAC correlate no nodal metastasis in SNB. In such patient, there is a possibility that SNB might be omitted in the future.

Legal entity responsible for the study

St Luke\'s International Hospital

Funding

None

Disclosure

All authors have declared no conflicts of interest.

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76P - Computed tomography liver spleen ratio as predictive marker of liver injury in early breast cancer receiving neoadjuvant therapy from 2010-2016 (ID 923)

Presentation Number
76P
Presentation Topic
Breast cancer, early
Lecture Time
13:00 - 13:00
Speakers
  • A. Gerona
Authors
  • A. Gerona
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

There is no way of predicting who among our early breast cancer patients develop liver injury during neoadjuvant treatment. It is our aim to determine such event by determining Computed tomography liver spleen ratio (LS ratio) and comparing it to liver function test.

Methods

Retrospective review in the Philippines for Stage I-III invasive breast cancer. Computed tomography LS ratio was reviewed by one radiologist. LS ratio cut off values were tested of their accuracy in terms of sensitivity, specificity, negative, and positive predictive values wherein a computed AUC of > 0.70 is considered significantly valid predictive markers.

Results

Total of 35 patients with average age of 53.91 years old, 57% had stage IIIB cancer. Patients’ average liver spleen ratio was 1.10±0.30 at the start, then, it slightly increased towards the end of the treatment (1.13±0.32). SGPT (37.43 to 35.09, p = 0.479) changed from start to end of treatment. Higher rates of liver injury at the start of treatment were as follows, 1(100%) with DOCETAXEL-TRASTUZUMAB, FAC (1,100%), and TAC (1, 11.1%). End of treatment, liver injury were noted among those with AC (1,50%), FAC (1,100%), EPIRUBICIN, DOCETAXEL (1,25%), and TAC (1,11.1%). Liver spleen ratio is significantly correlated with SGPT (r= -0.541, p = 0.001). At end of treatment, LS ratio is correlated with SGPT (r = -0.464, p = 0.005). LS ratio has higher sensitivity at start of treatment 100% at cut off 0.52, while at end of treatment the cut off was 0.87 has higher sensitivity (100%) in predicting liver injury. Based on AUC, LS ratio at the end of treatment showed higher accuracy (AUC =0.597) indicating the LS ratio can be utilized as marker for predicting liver injury.

Conclusions

Higher rates of liver injury at the start of treatment were seen those given Docetaxel- Trastuzumab, FAC and TAC. No liver injury for patients with hormonal treatment. End of treatment, liver injury seen in receiving anthracycline- based regimen. Liver spleen ratio is significantly correlated with SGPT. LS ratio at the end of treatment showed higher accuracy indicating the LS ratio be utilized as marker for predicting liver injury.

Legal entity responsible for the study

N/A

Funding

None

Disclosure

All authors have declared no conflicts of interest.

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Breast cancer, early Poster lunch Poster Display session

77P - Impact of apparent diffusion coefficient for the prediction of responses in patients with breast cancer treated with neoadjuvant chemotherapy (ID 1018)

Presentation Number
77P
Presentation Topic
Breast cancer, early
Lecture Time
13:00 - 13:00
Speakers
  • Y. Mizuno
Authors
  • Y. Mizuno
  • K. Nakamura
  • M. Shizuku
  • T. Mori
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

Neoadjuvant chemotherapy (NAC) results in a pathologic complete response (pCR), which has been shown to be associated with disease-free survival and overall survival. The apparent diffusion coefficient (ADC) indicates the stability of water molecules, and the ADC has been used to predict the response of solid tumors to chemotherapy. We therefore evaluated the ability of dynamic contrast-enhanced MRI (DCE-MRI) and diffusion-weighted imaging (DWI) to help predict pCR in patients with breast cancer treated with NAC.

Methods

From August 2013 to July 2016, 39 patients (mean age, 53 years; age range, 31–72 years) were treated with the nanoparticle albumin-bound paclitaxel (nab-PTX) (260 mg/m2; q3w for 4 cycles) ± concurrent trastuzumab (8mg, 6mg/Kg; q3w for 4 cycles) followed by the FEC100 (5-fluorouracil/epirubicin/cyclophosphamide, 500/100/500 mg/m2; q3w for 4 cycles). pCR was defined as the absence of any residual invasive cancer or ductal carcinoma in situ. Radiologic complete response (rCR) was defined as the absence of tumor enhancement. The ADC ratio (post FEC ADC/pre nab-PTX ADC) was calculated.

Results

Tumor phenotypes were found to be triple negative (TN) (n = 20) and human epidermal growth factor receptor 2 (HER2) positive (n = 19). pCR was achieved in 21 patients [54%]. rCR was observed in 17 patients [44%] . The mean pre nab-PTX ADC and ADC ratios were not associated with pCR in either phenotype (p = 0.57, p = 0.379 for TN disease; and p = 0.238, p = 0.168 for HER2-positive disease). By using receiver operating characteristic (ROC) analysis with the ADC ratio, the area under the curve (AUC) was 0.525 [95% confidence interval (CI): 0.24–0.811] in TN disease and 0.722 [95% CI: 0.449–0.995] in HER2-positive disease. According to radiologic responses and pathological responses, the ADC ratio in rCR plus pCR in TN disease was not changed among other response groups (ADC: 3.68±2.91), whereas it was higher than that in the other response groups in HER2-positive disease (ADC: 5.95±4.07).

Conclusions

A high ADC ratio in DWI plus rCR in DCE-MRI may be promising findings for the successful prediction of response in patients with HER2-positive breast cancer rather than in patients with TN breast cancer treated with NAC.

Legal entity responsible for the study

Yokkaichi Municipal Hospital

Funding

None

Disclosure

All authors have declared no conflicts of interest.

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78P - In vivo activation of mitochondrial pathway and cell cycle arrest through silymarin loaded iron nanoparticles as proficient nanocomplex system for triple negative breast cancer therapy (ID 1034)

Presentation Number
78P
Presentation Topic
Breast cancer, early
Lecture Time
13:00 - 13:00
Speakers
  • M. Paulpandi
Authors
  • M. Paulpandi
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

Nanoscale drug carriers play an important role in regulating the delivery, permeability, and retention of the drugs. Although various carriers have been used to encapsulate anticancer drugs, natural biomaterials are of great benefit for delivery and controlled release of drugs and their momentous activity in mice induced animal model.

Methods

We used the co-precipitation system to synthesize silymarin-iron composite nanoparticles for delivery and controlled release. Moreover, loaded particles were evaluated for its antiproliferation, cell cycle arrest, in vivo antitumor activity and apoptosis induction in triple negative breast cancer cells.

Results

(TNBC). DLS and TEM analysis confirmed that the size of synthesized iron oxide nanoparticles are about 60nm and extremely crystalline, spherical in nature. FTIR analysis confirmed that the silymarin molecules were conjugated with PEG coated iron oxide nanoparticles. X-ray diffraction pattern indicated that the iron nanoparticles were highly pure nature. Silymarin loaded nanoparticles showed a controlled release profile in response to diverse levels of pH. The particle mediated cytotoxicity was determined in MDA-MB-231 cancer cells and not found any adverse effect in normal cell HBL-100. We found that significant cell cycle arrest at various phases in the treated cancer cells and subsequent apoptotic cell death was evidenced with AO/EtBr, DAPI and PI of fluorescence microscopic analysis. TUNEL assay evidenced that DNA damage occurred in the treated cells. It could able to regulate the apoptotic and anti-apoptotic proteins. Moreover, the nanocomplexes are significantly reducing the tumor volume in tumor induced mice model.

Conclusions

Our findings have clearly demonstrated that silymarin loaded iron oxide nanoparticles could have efficiently deliver the drug of interest at the site of inflammation, initiate and execute the mitochondrial mediated apoptotic process in both in vitro and in vivo model.

Clinical trial identification

Just initial..

Legal entity responsible for the study

N/A

Funding

None

Disclosure

All authors have declared no conflicts of interest.

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79P - Evaluation of tissue computed tomography number changes and dosimetric shifts after conventionally fractionated irradiation in patients undergoing breast conserving surgery (ID 1939)

Presentation Number
79P
Presentation Topic
Breast cancer, early
Lecture Time
13:00 - 13:00
Speakers
  • D. Lee
Authors
  • D. Lee
  • Y. Lee
  • J. Kim
  • J. Lee
  • Y. Kim
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

The aim of this study was to assess tissue computed tomography (CT) number changes and corresponding dosimetric shifts in repeatedly performed simulation CT (re-sim CT) scans after conventionally fractionated irradiation in breast cancer patients.

Methods

A total of 28 breast cancer patients who underwent breast conserving surgery were enrolled in this study. All patients had received 50.4 Gy of conventionally fractionated irradiation and underwent re-sim CT scans for tumor bed boost. For evaluation of dosimetric shifts between initial and re-sim CT scans, electron boost plans in the same field size, same monitor unit with source-to-skin distance (SSD) 100cm were conducted. Dosimetric parameters (D105%, D103%, D100%, D98%, D95%, D90%: Dx% indicates volumes which receive X% of prescribed doses) between initial and re-sim CT scans were compared. The CT number data (CTmean, CTmax, CTmin) of original and irradiated CT (re-sim CT) scans from each representative structure (lung, rib bone, soft tissue, muscle, etc) were examined and recruited.

Results

CT numbers showed highly variable changes. Soft tissue CTmean and muscle CTmax/CTmin showed statistically and significantly increased values in re-sim CT compared with original CT scans. Rib bone CTmean/CTmin showed statistically and significantly decreased values in re-sim CT compared with original CT scans. Other CT number values showed no statistically significant changes. Among dosimetric parameters, only D105% (p = 0.015, mean 3.07cc versus 1.63cc) and D103% (p = 0.017, mean 13.8cc versus 11.9cc) showed statistically increased values in re-sim CT compared with original CT scans.

Conclusions

CT number changes after conventionally fractionated irradiation were different according to the tissue component. For electron boost plans, implementation of re-sim CT might be considered because significant dosimetric factor changes were observed especially in the high dose areas (hot spots; D105% andD103%).

Legal entity responsible for the study

CMC IRB Ethics Committee

Funding

None

Disclosure

All authors have declared no conflicts of interest.

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Breast cancer, locally advanced Poster lunch Poster Display session

80P - Incidence of permanent chemotherapy-induced alopecia among breast cancer patients: A five-year prospective cohort study (ID 1407)

Presentation Number
80P
Presentation Topic
Breast cancer, locally advanced
Lecture Time
13:00 - 13:00
Speakers
  • D. Kang
Authors
  • D. Kang
  • I. Kim
  • D. Lee
  • J. Ahn
  • J. Park
  • E. Guallar
  • J. Cho
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

While chemotherapy-induced alopecia is considered temporary and usually reversible within 1-6 months after chemotherapy, some patients report persistent alopecia several years after chemotherapy. The frequency of long-term permanent chemotherapy-induced alopecia (PCIA) and hair related changes is unknown. This study aimed to assess the incidence of PCIA among breast cancer patients by quantifying changes in hair density and thickness before chemotherapy, after two cycles of chemotherapy, and one, three, six, and 36 months after completion of chemotherapy.

Methods

This was a prospective cohort study of 61 patients 18 years of age or older with a postoperative diagnosis of stage I to III breast cancer who received adjuvant chemotherapy between February and September 2012 at an outpatient breast cancer clinic in Korea. Objective hair density and thickness were measured using a noninvasive bioengineering device.

Results

At 6 months after completion of chemotherapy, 11.5% and 30.8% of patients experienced PCIA in terms of hair density and thickness, which did not recover until after 36 months after completion of chemotherapy. Patients who received a combination of doxorubicin and cyclophosphamide followed by four additional cycles of paclitaxel were more likely to experience PCIA compared to patients with other type of chemotherapy. Patients who had PCIA were more likely to have significantly lower body image compared to patients without PCIA.

Conclusions

Permanent and severe alopecia is a common side effect of breast cancer adjuvant chemotherapy. Additional research is necessary to translate these findings into interventions for improving distress due to permanent alopecia in breast cancer patients after completion of chemotherapy.

Legal entity responsible for the study

Samsung Medical Center

Funding

This research was supported by Basic Science Research Program through the National Research Foundation of Korea(NRF) funded by the Ministry of Education (grant number: 2017R1D1A1B03031654).

Disclosure

All authors have declared no conflicts of interest.

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81P - Quantitation of cell loss in breast cancer during neoadjuvant treatment (NACT) assessed by serum thymidine kinase protein concentration (sTK1) (ID 1693)

Presentation Number
81P
Presentation Topic
Breast cancer, locally advanced
Lecture Time
13:00 - 13:00
Speakers
  • B. Tribukait
Authors
  • B. Tribukait
  • K. Jagarlamudi
  • J. Bergh
  • T. Hatschek
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

NACT of early breast cancer (BC) is intended to facilitate less extensive surgery by downstaging and provides the opportunity to study tumor response due to treatment. TK1 has a key function in DNA synthesis and repair responsible for maintaining the nucleoid pool balance by salvage and recycle thymidine from extracellular sources. Normally, TK1 is synthesized during S-phase, inactivated at mitosis and not leaked in connection with cell death. In contrast, release of TK1 into blood by necrosis or apoptosis is typical in malignancies.

Methods

We quantified cell loss using TK210 ELISA® for serial measurements of sTK1 in blood from 145 BC patients undergoing epirubicin/docetaxel +bevacizumab NACT therapy. sTK1 was related to clinical/radiological response after cycle (Cy) 2, 4 and 6, pathologic response, and disease free survival.

Results

Base-line sTK1 3-doubles 48h after treatment to plateau levels but declines during the 3 weeks rest between courses. sTK1 measured after treatment arrest periods correlated, after 4 cycles of treatment, significantly with clinical/radiological response during treatment and pathologic response at surgery. Surprisingly, the 48 h plateau values are highest in pT0, followed by pT3, pT2 and lowest in pT1. Disease free survival (median follow-up 49 mo.) ranged between 29.7% in pT0 and 5.7% in pT1 and is significantly related to sTK1.

Conclusions

Proliferation and cell loss are responsible for tumor growth and response to therapy. By now, no quantitation methods for cell loss are available. In this study TK1 has been proven to be a significant predictor of treatment response in NACT. sTK1 is a promising method for treatment related response and clinical drug development.

Clinical trial identification

EudraCT Number: 2007-005858-23

Legal entity responsible for the study

Karolinska Institute

Funding

Karolinska Institute

Disclosure

B. Tribukait: The author has stocks in AroCell. K.K. Jagarlamudi: I am working at AroCell AB.

All other authors have declared no conflicts of interest.

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82P - Indian triple-negative breast cancer – immune, molecular and clinical landscape (ID 1897)

Presentation Number
82P
Presentation Topic
Breast cancer, locally advanced
Lecture Time
13:00 - 13:00
Speakers
  • A. Sadanandam
Authors
  • A. Korlimarla
  • C. Ragulan
  • J. Prabhu
  • H. Shankaranarayana
  • M. Cheang
  • T. Sridhar
  • A. Sadanandam
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

Indian triple-negative breast cancers (TNBC) make up a substantially higher proportion of breast cancers than in developed countries (approximately 30% vs. 15-20%, respectively). Hence, effective management of TNBC requires identification of molecular factors that drive the heterogeneity including immune genes. Our goal was to perform a comprehensive analysis of the molecular and immune landscapes of TNBCs in India and compare it with the Western population.

Methods

A well-characterised cohort of 42 Indian breast cancer patient samples were used for this study. Unsupervised consensus clustering of gene expression profiles was performed to identify TNBC subtypes and was compared with that of the METABRIC data. Later, the subtypes were associated with mutations, immune cell enrichment and other clinical outcomes.

Results

Our results showed at least three immune-related subtypes (2 immune-enriched and 1 immune-dormant) of Indian TNBC. We arrived at a signature of 25 genes of which certain genes expressed in immune-enriched groups were related to cells from B, CD4 T, natural killer, macrophage and monocytes. Interestingly, 57% of the dense infiltrated tumors overlapped with the one of the immune-enriched subtype which showed a better survival. We validated these subtypes using METABRIC data and observed significant differences in overall survival (p = 0.01). Interestingly, proportion of better prognosis tumors is lower in our series as compared to METABRIC (23% Vs 58%) indicating greater proportion of more aggressive phenotype of Indian TNBCs.

Conclusions

Overall, this is the first study, to our knowledge, to profile large-scale Indian TNBCs and identify heterogeneity associated with disease prognosis and immune response. Future study warrants the validation and clinical utility of this classification to guide the subtype-specific therapy in Indian patients with TNBC.

Legal entity responsible for the study

Anguraj Sadanandam

Funding

None

Disclosure

A. Sadanandam: • Entitled to a share of royalty received by the licensor for a patent entitled “Colorectal cancer classification with different prognosis and therapeutic responses” – Patent number PCT/IB2013/060416 filed 26-Nov-2013, EPFL, Lausanne, Switzerland. • Molecular predictors of therapeutical response to specific anti-cancer agents -13/401,780, 21-Feb-2012, LBNL, Berkeley, CA, USA.

All other authors have declared no conflicts of interest.

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83P - Circulating tumor DNA detection in primary breast cancer patients by targeted sequencing: Consistency with tumor DNA and factors influencing detection (ID 1831)

Presentation Number
83P
Presentation Topic
Breast cancer, locally advanced
Lecture Time
13:00 - 13:00
Speakers
  • Z. Yidong
Authors
  • Z. Yidong
  • W. Changjun
  • Z. Yanyan
  • G. Yuhua
  • G. Yanfang
  • P. Li
  • Y. Ling
  • Y. Xin
  • X. Xuefeng
  • S. Qiang
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

Breast cancer is the most frequently diagnosed cancer worldwide in females with high mortality. As a noninvasive means to monitor the tumor genomes, circulating tumor DNA(ctDNA) detection has been applied to predict relapse and prognosis. However, systematic evaluation of ctDNA detection in plasma from patients with primary breast cancer(PBC) has not been performed. The aim of the study is to comprehensively assess the ctDNA detection and explore the factors affecting the release of ctDNA in patients with PBC.

Methods

71 females (8 stage I, 18 stage II, 38 stage III, 7 stage IV) with PBC newly diagnosed in Peking Union Medical College Hospital were selected in 2016. We analyzed genomic alterations of tumor tissues and matched plasma samples before the patients accepted any treatment by targeted sequencing in 1,021 cancer-associated genes.

Results

Of the 71 patients, 273 somatic mutations were detected in 71 tumor tissues, and 122 somatic mutations were detected in 49 plasmas; consistent mutations were observed in 44 patients. The concordance rate of plasma with tumor tissue was 61.97% and detection rate of it was 69.01%. 21 mutations including BRAF, GNAS, PTEN, were observed only in plasmas but not in tumor tissues. Consistent mutations were mainly TP53 and PIK3CA. The ctDNA detection rate was ly associated with tumor size (P=0.03) and lymph node metastasis or not(P=0.005), while it showed no significant differences with various age groups, HR status, Her2 amplification status, Ki67 levels and clinical pathological subtypes.

Conclusions

The study provided evidence that ctDNA detection was a complementary approach for patients with PBC. It implied the PBC patients with larger tumor or lymph node metastasis were more likely to benefit from ctDNA detection.

Legal entity responsible for the study

Peking Union Medical College Hospital

Funding

None

Disclosure

All authors have declared no conflicts of interest.

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84P - Effective strength training for breast cancer patients: literature review (ID 1024)

Presentation Number
84P
Presentation Topic
Breast cancer, locally advanced
Lecture Time
13:00 - 13:00
Speakers
  • R. Ceseiko
Authors
  • R. Ceseiko
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

Breast cancer (BC) patients experience complex health and psychosocial challenges. Cancer and cancer treatment accompanied with an inactive lifestyle may further impair muscle strength and muscle force development characteristics. As a countermeasure exercise training has been increasingly implemented into the oncology setting the last 3 decades. Strength training can optimally target muscles and increased muscle strength may contribute to participation in daily life and improve a quality of life. However, the optimal type, intensity, and frequency of strength training, as a part of the treatment, that will most enhance muscle strength is yet unknown.

Methods

The purpose of this review is thus twofold: (I) review the literature with regards to how strength training can be used as part of BC treatment and (II) determine key factor that contributes to effective strength training. Published literature search was conducted in PubMed/MEDLINE database between January 2016 and February 2017. Total 50 articles were included in the current review using keywords (breast neoplasms physical activity strength training).

Results

Christensen, Jones et al. (2014) examined newly diagnosed cancer patients with mixed diagnoses (lung, gastric, colorectal, breast, and pancreas cancer), these patients had 0.9 kg lower muscle mass compared with healthy controls before initiation of cancer treatment, moreover during the course of adjuvant chemotherapy, early-stage BC patients lost 1.3 kg lean body mass (LBM), and continued to lose LBM after therapy was completed. BC survivors evaluated after completion of primary therapy displayed consistently 20–30% lower muscle strength compared with healthy individuals (Harrington, Padua et al. 2011). It has been concluded that intensity 66% of one repetition maximum (1RM) is the minimum to induce changes in muscle strength (McDonagh, Davies et al. 1984). Most physical activity interventions that have been used in BC studies combine endurance training with strength training and relaxation therapies (Baumann, Bloch et al. 2013), thus making difficult to assess an effect of training type. There has been a limited amount of studies on BC patients that include higher intensity strength training.

Conclusions

General consensus on strength training interventions for cancer patients was that training programs were well tolerated, safe and feasible and showed strength improvements that led to improved physical function and improved quality of life (Segal, Reid et al. 2003) (De Backer, Van Breda et al. 2007) (Battaglini, Mills et al. 2014). Recognizing that training intensity during strength training is a key factor to increase maximal muscular strength and rate of force development (RFD), strength training with an intensity higher than the adaptive threshold of 66 - 70% of 1RM may have been preferable to induce great physiological adaptations, thus enhancing faster recovery from specific cancer treatment.

Legal entity responsible for the study

Rūdolfs Cešeiko

Funding

None

Disclosure

All authors have declared no conflicts of interest.

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85P - Polymorphism of genes of DNA repair enzymes in patients with breast cancer (ID 908)

Presentation Number
85P
Presentation Topic
Breast cancer, locally advanced
Lecture Time
13:00 - 13:00
Speakers
  • G. Allayarovna
Authors
  • G. Allayarovna
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

The group of tumor suppressor genes includes genes encoding components of the DNA excision repair system, which plays an important role in maintaining the stability of the genome. The most important structural components of the DNA excision repair system are proteins encoded by the XPD, DPYD, and other genes.

Methods

50 women were examined with breast cancer, stages 3-4. The diagnosis of breast cancer was based on data from anamnesis, the results of X-ray, and morphological examinations. The age of the patients were from 27 to 74 years (mean age 54 ± 0.06 year). All patients received standard treatment. Patients received chemotherapy according to the CAF regimens (fluorouracil 600 mg/m2, doxorubicin 60 mg/m2, cyclophosphamide 600 mg/m2 on day 1, every 4 weeks) and FAC (fluorouracil 500 mg/m2, doxorubicin 50 mg/m2, cyclophosphamide 500 mg/m2 on the 1st day, every 3 weeks).

Results

Two types of DNA genes were studied: XPD (XPD Lys751Gln) and DPYD (DPYD D949V and DPYD_14 (1236G> A)) in breast cancer patients. A normal allele of the DPYD D949V gene (D/D 98 + 23bpAsp/Asp) was found in all the patients examined, and no normal allele (A/A-247bp) of the DPYD_14 gene (1236G> A) was detected in any patient. Among the examined patients, the heterochromic allele (A/G 247 + 126 + 121bp) of the DPYD_14 gene (1236G> A) was detected in 72% (n = 36) patients, the mutation gene (G/G 126 + 121bp) DPYD_14 (1236G> A) - in 28% (n = 14) patients. Analysis of the Lys751Gln polymorphism of the DPDD gene of XPD and D949V showed that the incidence of variant genotypes was almost the same in BC patients: the allele of the XPD Lys/Lys gene (A/A-273bp) and the DPYD Asp/Asp allele (D/D-98 + 23bp) were found in 100% of patients; Heterozygous Lys/Gln (A/C-273 + 207 + 66bp) and mutational Gln/Gln (C/C-207 + 66bp) alleles of the XPD gene,

Conclusions

According to our data, the study of XPD Lys751Gln and DPYD D949V genes in patients with breast cancer is inadvisable. The mutating genes DPYD_14 (1236G> A) were determined. In this connection, it is possible to continue our studies, both to gain knowledge in the development of breast cancer, and to study the chemoresistance of breast cancer patients.

Legal entity responsible for the study

Republican Cancer Research Center

Funding

None

Disclosure

All authors have declared no conflicts of interest.

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86P - Usefulness of neoadjuvant chemotherapy in patients with luminal HER2(-) locally advanced breast cancer (ID 1428)

Presentation Number
86P
Presentation Topic
Breast cancer, locally advanced
Lecture Time
13:00 - 13:00
Speakers
  • H. Kim
Authors
  • H. Kim
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

Neoadjuvant chemotherapy (NAC) represents the standard treatment for patients with locally advanced breast cancer. We evaluated the tumor response and clinical outcomes according to molecular subtypes in locally advanced breast cancer, and we sought to investigate the benefit of NAC among luminal HER2(-) type

Methods

Our study evaluated data of 3,452 patients who were operated with malignant breast cancer between January 2010 and December 2016. We retrieved prospectively collected data of 249 patients with cytological node-positive breast cancer who were treated with NAC and underwent axillary lymph node dissection (ALND). Expression of estrogen receptor (ER), progesterone receptor (PgR), HER2, and Ki67 were used to divide into 4 subtypes: luminal HER2(-) (ER+, PR+, HER2-), luminal HER2(+) (ER+ and/or PR+, HER2+), HER2-overexpression (ER-, PR- and HER2+) and triple-negative (ER-, PR-, and HER2-). We determined rates of breast-conserving surgery, axillary pCR and tumor response rate after chemotherapy by approximated biologic subtype

Results

Axillary pCR was achieved for 79 patients (32.4%) who underwent ALND after NAC in our study. The axillary pathologic complete remission (pCR) rates according to different subtypes are as follows: luminal HER(-), 26 of 114 (22.8%), luminal HER(+), 14 of 39 (35.9%), HER2-overexpression 19 of 44 (43.2%), and triple-negative, 20 of 47 (42.6%) (p = 0.023). Rates of breast-conserving conversion were not significantly different in patients with luminal HER2(-) (11.4%) than other tumor subtype (p = 0.833). The median tumor response rate was 47.1% for the 249 Patients. The clinical tumor response rate of the breast tumor and axillary LN after NAC was not significantly different in the patients with luminal HER2(-), compared with the patients with other tumor subtype(p = 0.343).

Conclusions

While axillary pCR is significantly less common among women with luminal HER2(-) type, these patients still benefit from NAC in the aspect of increasing tumor response rate and breast conservation rate.

Legal entity responsible for the study

Kim Hyung Suk

Funding

None

Disclosure

All authors have declared no conflicts of interest.

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87P - 70-gene signature, an encouraging prognostic tool to guide adjuvant therapy in early breast cancer (ID 1454)

Presentation Number
87P
Presentation Topic
Breast cancer, locally advanced
Lecture Time
13:00 - 13:00
Speakers
  • A. Cunquero Tomas
Authors
  • A. Cunquero Tomas
  • C. Avila Andrade
  • A. Fernandez Diaz
  • M. Meri Abad
  • I. Shaheen
  • L. Condori Farfan
  • A. Rodriguez Huaman
  • V. Sforza
  • F. Aparisi Aparisi
  • M. Safont Aguilera
  • A. Blasco Cordellat
  • M. Gil Raga
  • C. Caballero Diaz
  • A. Berrocal
  • M. Godes Sanz de Bremond
  • A. Pérez
  • V. Iranzo Gonzalez-Cruz
  • C. Camps Herrero
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

Prognosis of early breast cancer (EBC) after surgery seems to be tied to both clinical and molecular features. Based on this, the addition of adjuvant chemotherapy (ACT) in ER+ HER2-, moderately differentiated, low ER expression or moderate tumor burden EBC is made, assuming a predictive role of these features in ACT benefit. There are patients who, based on these data, could abstain ACT without an increase in the risk of early relapse or decrease in survival. It is in these patients that molecular platforms, either 70-gene (Mammaprint®) or 21-gene (OncotypeDx®) signatures, combined with clinical features, would help decision making, sparing toxicities to these patients.

Methods

We analyzed 89 of 850 first visits (2014/17) with ER+ HER2- EBC, <75 years, Stages IA, IB and IIA according to AJCC. They fulfilled any of the following risk factors: weak ER/PR staining, G2 nuclear and Ki67 14% -30%. The risk of relapse was classified according to clinical (immunohistochemistry), statistical (PREDICT®) and molecular characteristics (70-gene signature Mammaprint®), to assess ACT indication.

Results

Mean 57 year-old patients at diagnosis, 60% postmenopausal. 53% Luminal B, all Luminal type by Blueprint®. 79% T1 and 16% N1mic. Bad prognosis encouraging ACT in 57% and 33% of patients based on clinical and statistical characteristics, respectively. 36% ACT indication on molecular basis, 25% of reduction of ACT indication. In subgroup analysis, 55% of high-risk patients according to clinical criteria were low-risk Mammaprint, with 33% who went from low to high risk of relapse. This implies a 20% decrease in chemotherapy treatments. In addition, 2 or more clinical risk factors may predict a high-risk result in the 70-gene signature assay, with likeliness of poor prognosis and ACT potential benefit. With a median follow-up of 15 months, no relapses have been noticed.

Conclusions

Prognosis based on clinically significant reduction of the indication of ACT (around 25%) without affecting the rate of relapse has been noticed, with data suggesting prediction of gene-signature assay results according to the number of clinical risk factor present. A longer follow-up time and a larger number of patients are needed to confirm these results.

Legal entity responsible for the study

Consorcio Hospital General Universitario Valencia

Funding

None

Disclosure

All authors have declared no conflicts of interest.

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Breast cancer, locally advanced Poster lunch Poster Display session

88P - Role of HSP27 in trastuzumab resistance in HER2-overexpressing breast cancer (ID 1850)

Presentation Number
88P
Presentation Topic
Breast cancer, locally advanced
Lecture Time
13:00 - 13:00
Speakers
  • S. Hwang
Authors
  • S. Hwang
  • S. Choi
  • Y. Na
  • Y. Lee
  • Y. Kwon
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

Overexpression of human epidermal growth factor receptor 2 (HER2) takes place in approximately 25% of breast cancer patients. Trastuzumab (Herceptin®), a FDA-approved HER2-targeting monoclonal antibody, is widely considered as the first line therapy for this patient group. However, despite its clinical benefits, over 70% of the patients frequently suffer from secondary resistance to this drug within one year. Therefore, identifying the resistance mechanism and investigating new therapeutic markers are certainly in need.

Methods

To elucidate the in-depth molecular mechanism involved in the resistance, we established two HER2-positive breast cancer cell lines with trastuzumab-resistance. We applied lentiviral shRNA expression system, cell viability assay, real-time PCR, western blot analysis, immunoprecipitation assay, xenograft mouse model for target validation of HSP27 and further evaluation of new applicable small molecule to surmount the resistance.

Results

Unique changes in the expression pattern of HSP27 were observed and they showed positive correlation with HER2. We confirmed the interaction between HER2-HSP27 and found that stably silenced HSP27 induced degradation of HER2 and eventually increased susceptibility of trastuzumab-resistant BT474 to Herceptin®. Newly identified compound to overcome the resistance, effectively inhibited the activity of HSP27 by significantly inducing the formation of its abnormal dimers. The candidate compound down-regulated the HER2-related cell signaling pathway without affecting any kinase activities. It also reduced the level of nuclear HER2 and its transcriptional target, cyclin D1, both of which are mentioned to reduce the efficacy toward trastuzumab. The compound in combination with Herceptin®, showed remarkable synergism of anti-cancer effects in trastuzumab-resistant cell lines. Cotreatment of the compound and trastuzumab also significantly induced tumor regression of trastuzumab-resistant cell-implanted xenograft mouse, and also increased their survival rates.

Conclusions

Targeting HSP27 by mediating compound-mediated abnormal dimerization would be a novel strategy to overcome trastuzumab-resistance.

Legal entity responsible for the study

Ewha Womans University

Funding

Bio & Medical Technology Development Program (NRF2014M3A9A9073 908) of the National Research Foundation of Korea (NRF).

Disclosure

All authors have declared no conflicts of interest.

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Breast cancer, locally advanced Poster lunch Poster Display session

89TiP - KEYNOTE-355: Randomized, double-blind, phase III study of pembrolizumab (pembro) + chemotherapy (chemo) vs placebo (pbo) + chemo for previously untreated, locally recurrent, inoperable or metastatic triple-negative breast cancer (mTNBC) (ID 1242)

Presentation Number
89TiP
Presentation Topic
Breast cancer, locally advanced
Lecture Time
13:00 - 13:00
Speakers
  • J. Cortes Castan
Authors
  • J. Cortes Castan
  • Z. Guo
  • V. Karantza
  • G. Aktan
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

Pembro monotherapy demonstrated promising antitumor activity and acceptable safety in pretreated patients (pts) with PD-L1+ mTNBC in the phase Ib KEYNOTE-012 study. The addition of pembro to chemo may enhance antitumor activity. KEYNOTE-355 is a global phase III study comparing pembro + chemo to PBO + chemo in pts with locally recurrent, inoperable, and previously untreated TNBC/mTNBC.

Trial design

Eligible pts are ≥18 y, have centrally confirmed, locally recurrent inoperable TNBC or mTNBC not treated previously with chemo (prior [neo]adjuvant chemo allowed); measurable disease per RECIST v1.1; ECOG PS 0-1; ≥6 mo between definitive breast surgery or last dose of adjuvant chemo (whichever was last) and first disease recurrence (≥12 mo if prior treatment with same-class agent). Part 1 is an open-label, unblinded safety run-in of ∼30 pts distributed over 3 arms (pembro + nab-paclitaxel, pembro + paclitaxel, pembro + gemcitabine/carboplatin). Part 2 is a double-blind, PBO-controlled study of ∼828 pts randomized 2:1 to pembro 200 mg Q3W + chemo (nab-paclitaxel 100 mg/m2 on d 1, 8, and 15 every 28 d; paclitaxel 90 mg/m2 on d 1, 8, and 15 every 28 d; or gemcitabine 1000 mg/m2 + carboplatin AUC 2 on d 1 and 8 every 21 d) or PBO + chemo. Crossover is not allowed. Stratification factors are study chemo (taxane vs gemcitabine/carboplatin), prior therapy with same-class agent in (neo)adjuvant setting (yes/no), and tumor PD-L1 expression (+/-). Treatment will occur for ≤35 administrations (pembro/PBO only) or until confirmed disease progression, unacceptable toxicity, decision to discontinue, or withdrawal of consent. Primary end points are safety in part 1 and PFS (by RECIST v1.1, central radiology review) and OS in part 2. Secondary end points include ORR (by RECIST v1.1, central radiology review) and duration of response. AEs will be graded per NCI CTCAE v4.0. Responses will be assessed at wk 8, 16, 24, then at 9-wk intervals up to 1 y, and 12-wk intervals thereafter. An interim safety analysis will occur in part 1 after pts complete 1 treatment cycle.

Clinical trial identification

NCT02819518.

Legal entity responsible for the study

Merck & Co., Inc., Kenilworth, NJ, USA

Funding

Merck & Co., Inc., Kenilworth, NJ, USA

Disclosure

J. Cortes Castan: Advisory board: Roche, Celgene, AztraZeneca, Cellestia Biotech, and Biothera Honoraria: Roche, Novartis, Eisai, Celgene, Pfizer, Z. Guo, V. Karantza: Employment and stock ownership: Merck & Co., Inc. G. Aktan: Employment and stock ownership: Merck & Co., Inc. Travel expenses: Merck & Co., Inc.

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Breast cancer, locally advanced Poster lunch Poster Display session

90TiP - A phase Ib trial of xentuzumab and abemaciclib in patients with locally advanced or metastatic solid tumors, hormone receptor-positive (HR+), HER2-negative (HER2-) breast cancer (BC; +/- endocrine therapy), or non-small-cell lung cancer (NSCLC) (ID 1419)

Presentation Number
90TiP
Presentation Topic
Breast cancer, locally advanced
Lecture Time
13:00 - 13:00
Speakers
  • D. Yee
Authors
  • D. Yee
  • A. Prat
  • M. Sablin
  • H. Iwata
  • E. Johnston
  • T. Bogenrieder
  • J. Serra
  • H. Hua
  • P. Lo Russo
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

The insulin-like growth factor (IGF) and the cyclin D-cyclin-dependent kinase (CDK) 4/6-retinoblastoma pathways have been implicated in the pathogenesis and resistance mechanisms of various cancers, including HR+, HER2- BC and NSCLC. IGF ligand-dependent signaling via the IGF receptor results in upregulation of cyclin D1, and subsequent progression through the cell cycle, thus providing a rationale for simultaneous inhibition of IGF and CDK4/6. This trial assesses the maximum tolerated dose (MTD), recommended phase II dose (RP2D), safety, and preliminary efficacy of the IGF ligand-neutralizing antibody, xentuzumab, in combination with abemaciclib, a selective inhibitor of CDK4 and 6, +/- endocrine therapy, in pts with solid tumors.

Trial design

Study BI 1280.18 is a phase Ib multicenter, non-randomized, open-label, dose-escalation trial with four dose-finding cohorts (Cohorts A–D) and two expansion cohorts (Cohorts E, F). Pts must be aged ≥18 yrs (≥20 for Japan), with measurable or evaluable disease, adequate organ function, ECOG PS ≤ 1, and unresectable advanced/metastatic solid tumors after failure on standard therapy (Cohort A), postmenopausal locally advanced/metastatic HR+, HER2- BC (Cohorts B–D, F), or stage IV NSCLC after 1–2 lines of therapy and failure after platinum-based chemotherapy and immunotherapy (Cohort E). CDK4/6 inhibitor-naïve pts (Cohorts A–E) and pts who have received prior CDK4/6 inhibitors (palbociclib or ribociclib) plus aromatase inhibitors (Cohort F) are included. Pts will receive either xentuzumab plus abemaciclib alone (Cohorts A, E) or in combination (at MTD defined in Cohort A) with letrozole (Cohort B), anastrozole (Cohort C), or fulvestrant (Cohorts D, F [at MTD for cohort D]). Primary endpoints are MTD and/or RP2D (Cohorts A–D) and objective response (Cohorts E, F). Further efficacy outcomes, pharmacokinetics, safety, and tolerability will also be assessed in all cohorts. This study will be conducted in the USA, Europe, and Japan. Pt screening started in May 2017. Target enrollment is ∼88 pts.

Clinical trial identification

NCT03099174; 1280.18.

Legal entity responsible for the study

Boehringer Ingelheim

Funding

Boehringer Ingelheim

Disclosure

A. Prat: Advisory board for Nanostring Technologies. E.L. Johnston: Owns stocks in and is an employee of Eli Lilly and Company. T. Bogenrieder: Employee of Boehringer Ingelheim and has stocks in Roche, Seattle Genetics and Immunogen. P. LoRusso: Served on advisory boards for Alexion, Ariad, CytomX, GenMab, Glenmark, Halozyme, Ignyta, Menarini, Novartis, Omniox. She served on a data safety monitoring board for Agios. She also was a member of imCORE Alliance with Roche-Genetech.

All other authors have declared no conflicts of interest.

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Breast cancer, metastatic Poster lunch Poster Display session

97P - Phase II trial of eribulin and S-1 combination therapy for advanced or recurrent breast cancer (ID 1483)

Presentation Number
97P
Presentation Topic
Breast cancer, metastatic
Lecture Time
13:00 - 13:00
Speakers
  • T. Iwasa
Authors
  • T. Iwasa
  • J. Tsurutani
  • Y. Mizuno
  • Y. Kojima
  • T. Takashima
  • N. Matsunami
  • T. Morimoto
  • J. Yamamura
  • S. Ohtani
  • Y. Tanabe
  • S. Watanabe
  • R. Kato
  • H. Tanino
  • S. Tokunaga
  • H. Abe
  • S. Tsuyuki
  • F. Hara
  • T. Takano
  • Y. Komoike
  • K. Nakagawa
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

Eribulin is a non-taxane microtubule dynamics inhibitor that has been proven to prolong overall survival in patients with advanced and recurrent breast cancer .S-1, an oral anticancer drug, composed of tegafur, gimestat and otastat potassium, has demonstrated non-inferiority in overall survival (OS) to taxane as first-line chemotherapy for metastatic breast cancer (MBC).We previouly reported phase I trial results for the combination of these drugs with an overall response rate of 41.7% and median progression free survival (PFS) of 7.6 months. George W et.al (J Clin Oncol 2003) suggested that estrogen receptor negativity, the presence of three or more sites of disease, a short disease-free interval (1 to 24 months), and prior systemic therapy all predicted for impaired overall survival in their multivariate analysis. Considering these factors, we conducted a multicenter phase II study of this combination to further evaluate its safety and efficacy.

Background

Eribulin is a non-taxane microtubule dynamics inhibitor that has been proven to prolong overall survival in patients with breast cancer. S-1, an oral anticancer drug, has demonstrated non-inferiority in overall survival (OS) to taxane as first-line chemotherapy for metastatic breast cancer (MBC). We previouly reported phase I trial results for the combination of these drugs with an overall response rate of 41.7% and median progression free survival (PFS) of 7.6 months. George W et.al (J Clin Oncol 2003) suggested that estrogen receptor negativity, the presence of three or more sites of disease, a short disease-free interval (1 to 24 months), and prior systemic therapy all predicted for impaired overall survival in their multivariate analysis. Considering these factors, we conducted a multicenter phase II study of this combination to further evaluate its safety and efficacy.

Methods

Recurrent or advanced breast cancer patients previously treated with anthracycline or taxanes were enrolled from September 2014 to May 2016. Patients received Eribulin 1.4 mg/m2 day1 and day8 intravenously and S-1 50 mg/m2 from day1 to day14 orally. Primary objective was to investigate safety and efficacy. Secondary objectives were to evaluate PFS, OS and clinical benefit rate (CBR) using Response Criteria in Solid Tumors (RECIST).

Results

Thirty-two patients were enrolled this trial and 30 patients were evaluable. Objective response rate was 36.7%. There were 3 [10%] complete responses, 8 [26.7%] partial responses and 11 [36.7%] stable diseases. This combination therapy had a manageable safety profiles consistent with the known adverse effects of both drugs. The most common grade3-4 adverse events were neutropenia (22 [73.3%] of 32 patients), leukopenia (13 [43.3%] of 32 patients), febrile neutropenia (3 [9.4%] of 32 patients) and peripheral neuropathy (4 [12.5%] of 32 patients). CBR was 46.7%. The median overall survival and the median PFS was not reached.

Conclusions

We showed tolerability and clinical activity in this combination therapy in a subset of patients with poor prognosis. Eribulin in combination with S-1 may represent a promising treatment option for advanced or recurrent breast cancer patients.

Legal entity responsible for the study

Eisai

Funding

Eisai

Disclosure

All authors have declared no conflicts of interest.

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Breast cancer, metastatic Poster lunch Poster Display session

98P - Effect of postmastectomy radiotherapy on breast cancer with isolated tumor cells or micrometastases in regional lymph nodes: A propensity score matched analysis using the SEER database (ID 1526)

Presentation Number
98P
Presentation Topic
Breast cancer, metastatic
Lecture Time
13:00 - 13:00
Speakers
  • W. Xia
Authors
  • Q. Zheng
  • W. Xia
  • Q. Lu
  • S. Wang
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

Postmastectomy radiotherapy (PMRT) has been strongly considered for patients with 1-3 positive axillary nodes (ALNs). In addition, the indications for PMRT are expanding to patients with negative ALNs but have multiple high-risk recurrence factors. However, For patients with isolated tumor cells. We aimed to determine the effects of PMRT on survival of patients with ITCs or ALNs micrometastases of breast cancer.

Methods

We identified patients with ITCs or ALNs micrometastases after mastectomy from the Surveillance, Epidemiology, and End Results database from 2004 to 2014. Overall survival (OS) and breast cancer-specific mortality (BCSM) were compared among patients received PMRT or not, using propensity score-matched analyses. Cox proportional hazards models and competing-risk models were performed in OS and BCSM analyses, respectively.

Results

We identified 11,622 eligible cases. PMRT was administered to 1,728 patients. Treatment was less frequent among patients who were older, patients with high-income, and patients with right-side tumor. OS at 5 years and 10 years were 88.1% and 74.2% in PMRT group, and were 87.8% and 77.3% in non-PMRT group, respectively. Five-year and 10-year cumulative BCSM rate were 6.4% and 12.3% in PMRT group, and were 6.6% and 14.1% in non-PMRT group, respectively. OS and BCSM were unaffected by PMRT after adjusting for multiple confounders (OS, hazard ratio, 0.92; 95% CI, 0.74 to 1.16; BCSM, subhazard ratio, 0.89; 95% CI, 0.67-1.18).

Conclusions

To our knowledge, this is the largest study to date of the effect of radiotherapy on survival in breast cancer with ITCs or ALN micrometastases. In this population-based study, we do not find survival benefit of PMRT on patients with ITCs or ALN micrometastases.

Legal entity responsible for the study

Sun Yat-sen University Cancer Center

Funding

None

Disclosure

All authors have declared no conflicts of interest.

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Miscellaneous Poster lunch Poster Display session

99P - Frequency of pathogenic mutation in patients at high risk for hereditary breast cancer (ID 1119)

Presentation Number
99P
Presentation Topic
Miscellaneous
Lecture Time
13:00 - 13:00
Speakers
  • H. Shin
Authors
  • H. Shin
  • T. Yoo
  • H. Lee
  • H. Moon
  • D. Noh
  • W. Han
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00
Breast cancer, metastatic Poster lunch Poster Display session

100P - Impact of perioperative fluoropyrimidines on the efficacy of capecitabine in patients with advanced breast cancer: A retrospective study (ID 1155)

Presentation Number
100P
Presentation Topic
Breast cancer, metastatic
Lecture Time
13:00 - 13:00
Speakers
  • S. Iizumi
Authors
  • S. Iizumi
  • A. Shimomura
  • T. Shimoi
  • K. Sudo
  • E. Noguchi
  • K. Yonemori
  • C. Shimizu
  • Y. Fujiwara
  • K. Tamura
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

It is unclear whether perioperative fluoropyrimidine (FP) use impacts the efficacy of capecitabine in advanced breast cancer treatment.

Methods

Medical records of patients with advanced breast cancer who received capecitabine between 2008 and 2016 at National Cancer Center Hospital (Tokyo, Japan) were reviewed. Progression-free survival (PFS), overall survival (OS), tumor response, and adverse events (AEs) were compared between a FP group (prior perioperative FP use) and a non-FP group (no prior FP use). To evaluate the effect of prior perioperative FP use on survival outcomes, hazard ratios (HRs) for PFS and OS were estimated for the FP group compared with the non-FP group.

Results

A total of 289 patients (FP group: n = 106; non-FP group: n = 183) were analyzed. Patient characteristics were similar between the two groups. The median recurrence-free interval (RFI) was 3.94 (range: 0.27-20.11) years in the FP group and 4.24 (range: 0.27-27.07) years in the non-FP group (p = 0.402). The FP group had poorer PFS than the non-FP group (univariate HR: 1.33; 95% confidence interval [CI]: 1.03-1.72, p = 0.028; multivariate HR: 1.33; 95% CI: 1.02-1.73; p = 0.034). However, OS was similar between the groups (univariate HR: 1.16; 95% CI: 0.84-1.62; p = 0.368; multivariate HR: 1.06; 95% CI: 0.74-1.51; p = 0.755). Multivariate HRs for PFS for the FP group with short RFI and long RFI (cutoff: RFI=4 years) separately were 1.56 (95% CI: 1.06-2.28; p = 0.025) and 1.20 (95% CI: 0.84-1.70; p = 0.326), respectively. With different cutoffs (RFI=3, 4, and 5 years), the ranges of adjusted HRs for PFS were 1.32-1.67 with short RFI, and 1.00-1.25 with long RFI. A trend for larger HR for the FP group with short RFI than with long RFI was also seen for OS with different cutoffs of RFI. The response rate (FP group vs. non-FP group) was 21.0% vs. 14.8% (p = 0.306), and the disease control rate was 59.9% vs. 54.5% (p = 0.422). There was no significant difference in AEs between the two groups.

Conclusions

Capecitabine can be used for patients with advanced breast cancer with FP use history, as OS does not correlate with prior FP use. For patients with FP use history, RFI may be a relevant factor for treatment selection.

Legal entity responsible for the study

National Cancer Center Hospital

Funding

None

Disclosure

All authors have declared no conflicts of interest.

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Breast cancer, metastatic Poster lunch Poster Display session

101P - The efficacy of eribulin mesylate with trastuzumab for locally advanced or metastatic HER2-positive breast cancer treated with prior pertuzumab and/or T-DM1: Results from a phase II, single arm, multicenter study (N-SOG 10 study) (ID 1656)

Presentation Number
101P
Presentation Topic
Breast cancer, metastatic
Lecture Time
13:00 - 13:00
Speakers
  • M. Fujii
Authors
  • M. Fujii
  • N. Tsunoda
  • M. Hattori
  • T. Murata
  • K. Akahane
  • K. Kamei
  • Y. Goto
  • T. Amemiya
  • K. Nishimae
  • T. Kubota
  • Y. Ito
  • Y. Kurumiya
  • M. Yoshihara
  • K. Nakanishi
  • T. Kikumori
  • M. Ando
  • M. Nagino
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

Eribulin mesylate (ERI) demonstrated a survival benefit in patients with locally recurrent or metastatic breast cancer who previously received 2 or more chemotherapy regimens. Recently, we conducted Phase II study about the efficacy of ERI with trastuzumab (ERI+TRA) as late-line therapy for locally advanced or metastatic HER2-positive breast cancer (UMIN000012350), and reported that objective response rate (ORR) and median progression-free survival (mPFS) were 17% and 4.6 months. However, some patients who received prior pertuzumab (PER) and/or T-DM1 were enrolled in that study, there are limited data on the efficacy of ERI+TRA in those patients. The aim of this study was to assess the efficacy of this combination therapy based on prior PER and/or T-DM1 use.

Methods

In primary phase II study, patients with locally advanced or metastatic HER2 positive breast cancer who previously received at least one chemotherapeutic regimen, received ERI at 1.4 mg/m2 intravenously (I.V.) on days 1 and 8 of each 21-day cycle with an initial TRA dose of 8 mg/kg I.V. on day 1, followed by 6 mg/kg of TRA on day 1 of each subsequent cycle. ORR, clinical benefit rate (CBR) and PFS were assessed in patients who had and had not received prior PER and/or T-DM1.

Results

Thirty-six patients (median age: 60.5 years) received ERI+TRA. 69.4% (n = 25) had previously treated with prior PER and/or T-DM1, defined as ‘prior’ patients. Remaining 30.6% (n = 11) without both agents were defined as ‘non-prior’ patients. In prior patients compared with non-prior patients, median number of prior treatment regimens was 4 (range, 1‐8) versus 3 (range, 1-7), respectively; ORR was 12.0% versus 27.3%, respectively; CBR was 24.0% versus 54.5%, respectively; mPFS was 4.3 versus 9.7 months, respectively.

Conclusions

ERI+TRA demonstrated lower efficacy than in non-prior patients, but CBR and PFS were 24.0% and 4.3 months, which was considered to be a clinically relevant treatment option in patients who received prior PER and/or T-DM1.

Clinical trial identification

UMIN000012350.

Legal entity responsible for the study

Nagoya Surgical Oncology Group

Funding

Eisai

Disclosure

All authors have declared no conflicts of interest.

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Breast cancer, metastatic Poster lunch Poster Display session

102P - Multicenter phase 2 trial of varlitinib versus lapatinib in combination with capecitabine in patients with HER2+ metastatic breast cancer (MBC) who failed prior trastuzumab therapy (ID 987)

Presentation Number
102P
Presentation Topic
Breast cancer, metastatic
Lecture Time
13:00 - 13:00
Speakers
  • S. Lee
Authors
  • S. Lee
  • S. Chen
  • M. Dai
  • G. Lee
  • C. Liu
  • A. Chan
  • H. Chang
  • L. Tseng
  • W. Chay
  • L. Chow
  • J. Peneyra
  • K. Rau
  • H. Wang
  • A. Guancia
  • M. Head
  • J. Chiu
  • B. Robinson
  • B. Lindmark
  • N. McIntyre
  • C. Hsieh
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

Varlitinib, a tyrosine kinase inhibitor of the ErbB family (EGFR, HER2 and HER4), showed anti-tumor activity in trastuzumab-resistant models and in patients with trastuzumab-resistant, chemotherapy-refractory MBC in a phase 1 study. This study compared the efficacy and safety of varlitinib plus capecitabine (VC) versus lapatinib plus capecitabine (LC) in HER2+ MBC patients who failed prior trastuzumab therapy.

Methods

The primary objective was to assess percentage change in tumor size at week 12. Objective response rate (ORR), safety and drug exposure were also assessed. Patients who received at least one dose of study treatment were included in primary analysis. Sensitivity analysis for primary objective and ORR were performed in patients who remained on study for more than 30 days.

Results

From Dec 2014 to Aug 2016, 24 patients were randomized to the VC arm (400mg BID) and 26 to the LC arm (1250mg QD) in 16 sites in 6 countries. Percentage of tumor size reduction was numerically higher in VC than LC (-31.00% vs. -19.37%, one-sided p = 0.132). ORR in the VC arm (40.9%) was similar to LC arm (45.5%), p = 1.000. Sensitivity analysis showed numerically superior ORR and statistically significant higher reduction of tumor size in VC compared to LC (60% vs. 45.5%, p = 0.508; mean, -34.6% vs.-19.4%, one-sided p = 0.075) All patients had at least 1 AE. Severe AE(s) were observed in 13 patients (54.2%) in the VC arm and 11(42.3%) in the LC arm. The most common AE was diarrhea (66.7%) in the VC arm and were diarrhea and palmar-plantar erythrodysaesthesia syndrome (both 50%) in the LC arm. Median intended exposure and percentage of intended dose were lower in the VC arm (115.5 days, 74.6%) indicating more frequent dose interruption, dose reduction and treatment discontinuation than the LC arm (135.0 days, 99.05%).

Conclusions

Sensitivity analysis showed greater tumor size reduction and improved ORR for VC arm when the combination was administrated for more than 30 days. Reduced intended exposure and dose intensity for the VC arm suggests a dose reduction of varlitinib may be considered when combined with capecitabine for the 2nd line treatment of HER2+ MBC.

Clinical trial identification

NCT02338245.

Legal entity responsible for the study

ASLAN pharmaceuticals

Funding

ASLAN pharmaceuticals

Disclosure

All authors have declared no conflicts of interest.

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Breast cancer, metastatic Poster lunch Poster Display session

103P - Efficacy of T-DM1 in patients with HER2-positive metastatic breast cancer previously treated with pertuzumab (ID 1223)

Presentation Number
103P
Presentation Topic
Breast cancer, metastatic
Lecture Time
13:00 - 13:00
Speakers
  • K. Matsui
Authors
  • K. Matsui
  • A. Yoshikawa
  • K. Oyama
  • Z. Nozaki
  • Y. Tanada
  • M. Earashi
  • K. Kiyohara
  • T. Nagata
  • W. Fukushima
  • T. Shimizu
  • K. Maeda
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

The standard therapy for primary treatment of HER2-positive metastatic breast cancer (MBC) is combination therapy of pertuzumab (PER), trastuzumab (HER) and docetaxel (DTX). Although the effectiveness of trastuzumab emtansine (T-DM1) after HER treatment has been reported, there are few reports on the effectiveness of T-DM1 for patients treated with PER. We retrospectively investigated the effectiveness of T-DM1 on HER2-positive MBC previously treated with PER.

Methods

Between October 2013 and June 2017, 79 patients with HER2-positive MBC were treated with PER. 44 patients were investigated the subsequent treatment. 34 patients received T-DM1, and 10 patients received treatment other than T-DM1 after PER treatment.

Results

Median treatment line was 3.0 (1-9) vs 4.0 (1-9) in the T-DM1 treatment and other than T-DM1 treatment, respectively. The response rate was CR 0% vs 0%, PR 36.0% vs 25%, SD 32.0% vs 62.5%, PD 32.0% vs 12.5%, respectively. The objective response rate was 36.0% vs 20.0%. The clinical benefit rate was 48.0% vs 50.0%. Median time to treatment failure was 6.6 months vs 2.9 months, respectively. There was a significant difference in median overall survival; median not reached vs 19.6 months (p = 0.04).

Conclusions

OS was significantly better with administration of T-DM1 after PER treatment. Based on the results of this study, it was confirmed that efficacy of T-DM1 in patients with HER2-positive metastatic breast cancer previously treated with PER.

Legal entity responsible for the study

Koshi Matsui

Funding

None

Disclosure

All authors have declared no conflicts of interest.

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Breast cancer, metastatic Poster lunch Poster Display session

104P - Clinical and pathological profile of patients with breast cancer in northwest Pakistani population (ID 1311)

Presentation Number
104P
Presentation Topic
Breast cancer, metastatic
Lecture Time
13:00 - 13:00
Speakers
  • A. Ali
Authors
  • A. Ali
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

Breast cancer (BC) is the most frequently diagnosed disease and a leading cause of death in females globally. BC is also common in Pakistani females and one out of every nine female is at risk of developing BC. Information on the clinico-pathologic (CP) data of BC is limited especially from the northwest part of Pakistan. The purpose of this study was to profile the CP data of BC. This will clearly help us in assessing the CP characteristics of the disease and in public health intervention measures.

Methods

Data were extracted from consecutive medical files of BC patients at the IRNUM Hospital, Peshawar, Pakistan from 2014 to 2016. Demographic, clinical and pathological data were profiled. Data were analyzed for descriptive statistics, independent sample t test and Chi square test. Logistic regression was performed by stratifying patients according to the disease stage as early stage (stage I and II, ES) and late stage (stage III and IV, LS).

Results

Data of 362 patients with breast cancer was profiled. The mean age at diagnosis was 47.8 years. 8% of the patients were nulliparous and 5.2% of the patients had a positive family history of BC. The most common symptom was a lump in breast (82%), and left breast (54%) was the most common location of tumor. Most of the patients presented with LS disease (65%). ER+, PR+ and HER2+ cases were 62%, 47% and 49% respectively. The tumour was localized in 75% of the cases, while multifocal in 25% of the cases. The mean age (47.8 yrs) in the ES breast cancer is not statistically different from the mean age (47.7 yrs) in the LS breast cancer (p = 0.99). Lymph node positivity is associated with LS disease (p < 0.001) and it predicts LS disease (OR = 17.1, p < 0.001). Vascular invasion and HER2+ are also associated with LS disease (p = 0.06, p = 0.07, trending statistical significance).

Conclusions

Due to delayed consultation, patients present with late stage disease irrespective of age of patients. Thus, there is an urgent need for public health outreach programs directed towards awareness campaigns and the need for routine breast cancer screening. In addition, positive family history may be evaluated as potential risk factors in our population. Finally, a significant number of patients are ER+/PR+ and HER2+, which may promise targeted therapy options.

Legal entity responsible for the study

Office of Research, Khyber Medical University, Peshawar

Funding

None

Disclosure

All authors have declared no conflicts of interest.

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Breast cancer, metastatic Poster lunch Poster Display session

105P - Cost-effectiveness analysis of exemestane versus chemotherapy in post-menopausal hormonal responsive advanced breast cancer patients (ID 988)

Presentation Number
105P
Presentation Topic
Breast cancer, metastatic
Lecture Time
13:00 - 13:00
Speakers
  • P. Sripan
Authors
  • I. Chitapanarux
  • R. Sruamsiri
  • P. Klunklin
  • P. Sripan
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

Breast cancer has become the most common cancer in Thai women since 2005. Unfortunately two thirds of the patients were diagnosed at advanced breast cancer (ABC) stage. Furthermore, most of these women were under the Universal Coverage by the government which does not provide sufficient coverage for certain critical medical treatments for ABC patients. The cost of treatments is even more of a pressing issue in Thailand. This study aimed to evaluate the cost-effectiveness of exemestane (EXE), a steroidal aromatase inhibitor (SAI), as treatment therapy following adjuvant non-steroidal aromatase inhibitor (NSAI) for hormonal responsive ABC in Thailand.

Methods

A Markov model was used to estimate the relevant costs and health outcomes over the patients' lifetimes using a social cost and benefit perspective. All future costs and outcomes were discounted at a rate of 3% per annum. The efficacy and cost of EXE and chemotherapy were based on a clinical trial that included a total of 18 post-menopausal hormonal responsive ABC patients. Utility values were derived directly from all patients using EQ-5D. Primary outcomes of interest were lifetime costs, quality adjusted life-years (QALYs) gained, and the incremental cost-effectiveness ratio (ICER) in US ($) per QALY gained. One-way and probabilistic sensitivity analyses (PSA) were conducted to investigate the effect of parameter uncertainty.

Results

In base case analysis, the EXE group had better clinical outcomes and lower lifetime costs. The incremental cost per QALY gained was US $-2,747 per QALY. The acceptability curve showed that the probability of EXE being cost-effective was 97% at the willingness to pay of 1 time of Thai Gross National Income per capita (GNI per capita), approximately US $4,673 per QALY gained.

Conclusions

At a social cost of paying 1 GNI per capita, EXE is highly effective and cost-saving regimen for the first-line treatment of post-menopausal ABC with hormone positive receptor in Thailand. This study provides key relevant information aiding policy makers to make informed decision making regarding resource allocation to include EXE into reimbursement plan.

Legal entity responsible for the study

Faculty of Medicine, Chiang Mai University

Funding

None

Disclosure

All authors have declared no conflicts of interest.

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Breast cancer, metastatic Poster lunch Poster Display session

106P - Eribulin mesylate for HER2- metastatic breast cancer; analyses of pattern of disease progression and outcomes from the real world (ID 1477)

Presentation Number
106P
Presentation Topic
Breast cancer, metastatic
Lecture Time
13:00 - 13:00
Speakers
  • J. Watanabe
Authors
  • J. Watanabe
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

The subanalysis of prospective randomized trials of E suggested E suppressed development of new lesion [NL] and it led to improvement of overall survival (Twelves, BCRT, 2015), however, behaviors of disease in real-world patients (pts) have not been well discussed.

Methods

Outcomes of HER2-MBC pts who received E at our institute from November 2011 to present were reviewed. Statistical analyses were performed using the chi-square test, the Kaplan-Meyer method.

Results

We identified total 128 (90 ER+, 38 ER-) HER2-MBC who received E at least 2 cycles in our institute. Median age at the initiation of E were as follows; overall, 58 (range 30-77); ER+, 60 (30-77); ER- 55.5 (32-71). Median number of regimens prior to E were as follows; overall, 1 (range 0-8); ER+, 1 (0-6); ER-, 2 (0-8). While all pts had a history of anthracycline and/or taxane in ER- subset, Number of involved organ were 2 (1-5) in overall and both subsets and no significant difference was seen in the pattern of visceral involvement. Most of (122/128, 95.5%) the pts was discontinued E therapy, and median time-to-treatment failure (TTF) were as follows; overall, 125.0 days (95% confidence interval [CI] 43.0-328.0); ER+, 134.0 days (95%CI 62.0-314.0); ER-, 104.0 (95%CI 42.0-230.0). Reasons for the discontinuation of E were as follows; progression of known lesion(s), 77 (63.1%); development of NL, 27 (22.1%), decrease of performance status, 11 (9.0%); intolerable toxicity, 6 (4.9%); other, 1 (0.9%). In ER- subset, development of NL was more frequently seen compared to ER+ subset, however, it was not statistically significant. (7/20 vs 10/67, P = 0.12, chi-square). Multivariate cox regression analyses disclosed some risk factors for TTF as follows; liver metastasis, hazard ratio [HR] 0.39, P < 0.05; soft tissue metastasis, HR 0.53, P < 0.05; ≥3 involved organs, HR 2.99, P < 0.05; taxane for early breast cancer, HR 2.50, P < 0.05. When limited to ER+ pts who received E as 2nd-line therapy (N = 40), only one (2.5%) pt developed NL and there was a positive relationship between TTF and OS after E (Spearman's roh=0.64, p < 0.0001).

Conclusions

Our single institutional review with some limitations disclosed eribulin monotherapy revealed equivalent effect shown in prospective studies.

Legal entity responsible for the study

Junichiro Watanabe

Funding

None

Disclosure

J. Watanabe: Advisory board member of Eisai Co., Ltd. Honoraria from Eisai Co., Ltd.

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Breast cancer, metastatic Poster lunch Poster Display session

107P - The utility of risk factors proposed in a prospective clinical trial in the management of ER-positive, HER2-negative metastatic breast cancer patients: Feedback from the real world (ID 1491)

Presentation Number
107P
Presentation Topic
Breast cancer, metastatic
Lecture Time
13:00 - 13:00
Speakers
  • K. Yoshitsugu
Authors
  • K. Yoshitsugu
  • J. Watanabe
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

Some risk factors (RFs) in the management of ER-positive, HER2-negative metastatic breast cancer (ER+HER2-MBC), such as a shorter disease-free interval (DFI), visceral involvement or high tumor burden, have been identified in prospective clinical trials; however, the utility of those RFs in the real world has not been well discussed.

Methods

We reviewed our medical records from 2002 to present to assess the utility of RFs (DFI≤24 months [DFI≤24M]; visceral metastases [VIS]; prior (neo)adjuvant anthracycline and/or taxane [A/T]; or ≥ 3 metastatic organs [≥3 ORG]) defined in the TURANDOT risk factor analyses (Brodowicz T, Br J Cancer, 2014), a first-line bevacizumab trial of HR+HER2-MBC patients. According to the analysis, patients with ≥2 RFs were classified as “high-risk (HiR)”, and others were classified as “low-risk (LoR)”. Statistical analyses were performed using the Kaplan-Meyer method and a multivariate COX regression analysis.

Results

We identified 311 ER+HER2-MBC (224 recurrent, 87 advanced) patients who underwent chemotherapy (CTx). The most common RF at the initiation of first-line CTx was VIS (N = 186, 59.8%), followed by A/T, ≥3 ORG and DFI≤24M. The distribution of RFs was as follows: 0 in 89 (28.6%), 1 in 93 (29.9%), 2 in 94 (30.2%), 3 in 30 (9.6%), and 4 in 5 (1.7%). The survival from the initiation of CTx (OSCTx) was significantly poorer in HiR patients than LoR ones (median 815.0 vs. 1062.0 days, p < 0.001, log-rank) in all MBC patients, as well as in 87 advanced BC patients (median 825.0 vs. 1160.0 days, P < 0.05, log-rank). There was no significant difference in the OSCTx between patients with 0 and 1 RF (P = 0.90). In addition, in recurrent BC (rBC) patients, there was no significant difference in the OSCTx between patients with 2 and ≥3 RFs (P = 0.10). Multivariate analyses revealed ≥3 ORG and DFI≤24M as significant RFs (P < 0.05) for all rBC patients (hazard ratios 1.61 and 1.49, respectively).

Conclusions

Our review suggests that RFs such as high tumor burden and shorter DFI identified in prospective randomized studies are applicable to patients in the real world, even with heterogeneous backgrounds.

Legal entity responsible for the study

Junichiro Watanabe

Funding

None

Disclosure

J. Watanabe: Honoraria from AstraZeneca Japan, Chugai Pharmaceuticals, Eisai, Novartis Pharma Japan, Taiho pharmaceuticals, and advisory board member of AstraZeneca Japan, Eisai.

All other authors have declared no conflicts of interest.

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Breast cancer, metastatic Poster lunch Poster Display session

108P - Does non-adherence result in worse clinical outcomes for hormone receptor-positive and HER2-negative metastatic breast cancer in premenopausal women? (ID 2022)

Presentation Number
108P
Presentation Topic
Breast cancer, metastatic
Lecture Time
13:00 - 13:00
Speakers
  • H. Kim
Authors
  • H. Kim
  • Y. Kim
  • S. Park
  • H. Lee
  • S. Lim
  • J. Kim
  • M. Heo
  • Y. Park
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

In this study, we observe the patterns initial palliative treatment for premenopausal patients with HR-positive/HER2-negative MBC and determine if non-adherence to clinical guidelines are associated with worse clinical outcomes in terms of progression-free survival (PFS) and overall survival (OS) in the South Korean population.

Methods

A retrospective review was performed for premenopausal patients diagnosed with HR-positive MBC between October 1997 and May 2016 who received palliative systemic treatments at a large tertiary medical center. Survival outcomes were analyzed according to the palliative treatment received prior to disease progression.

Results

The review identified a total of 272 premenopausal patients with HR-positive/HER2-negative MBC. The patients were young (median age, 39 years), as per the premenopausal criteria. Chemotherapy alone was first-line palliative treatment in 78 patients, with endocrine therapy as the initial treatment in 133 patients. In 57 patients, the first line treatment was switched from chemotherapy to endocrine treatment prior to any disease progression. Both progression free survival and overall survival were significantly longer for chemotherapy-endocrine therapy (median PFS 18.2 months and OS 85.2 months) than for chemotherapy-alone (median PFS 12.6 months and OS 45.5 months) or endocrine therapy-alone (median PFS 7.0 months and OS 57.3 months) (all P values < 0.01). In multivariate analysis, chemotherapy-endocrine therapy was an independent predictive value for improved PFS and OS (hazard ratio [HR] 0.33, 95% CI 0.20-0.52, P < 0.001; HR 0.38, 95% CI 0.19-0.73, P = 0.004).

Conclusions

In our study population, chemotherapy alone was not objectively inferior to endocrine therapy as the initial palliative treatment. In addition, chemotherapy followed by endocrine therapy was associated with objective higher response rate than endocrine therapy alone. Further studies should explore the relationship between non-adherent treatment patterns and patient outcomes across the largely premenopausal breast cancer populations across Asian countries.

Legal entity responsible for the study

Prof. Yeon Hee Park

Funding

None

Disclosure

All authors have declared no conflicts of interest.

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Breast cancer, metastatic Poster lunch Poster Display session

109P - Literature review of visceral and non-visceral metastatic breast cancer (ID 1094)

Presentation Number
109P
Presentation Topic
Breast cancer, metastatic
Lecture Time
13:00 - 13:00
Speakers
  • N. Begum
Authors
  • T. Mehmood
  • N. Begum
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

Differential efficacy of newly registered therapies in subgroups of metastatic breast cancer (mBC) is an important consideration for their subsequent use in clinical practice. In a systematic literature review, we evaluated differences in outcome regarding progression free survival (PFS), time to progression (TTP), overall survival (OS) and visceral versus non-visceral disease. The impact of HER2- and hormone receptor-status was also considered.

Methods

A systematic literature search (6362 hits) in the meta-Database PubMed was performed for the last 20 years. 257 studies (n = 126,291) were included for further analysis. 69 studies had published data for visceral vs non visceral disease including phase III trials. Out of these 69 studies we selected n = 16 studies (n = 13,083) which looked at the endpoints mentioned above. In order to achieve comparability, we extracted the information of hazard ratios (HR), confidence intervals (CI) and times in weeks (if available) for PFS, TTP, OS of the entire study population, which was divided into three groups: HER2-positive, HER2-negative, unknown HER2 status.

Results

No statistically significant difference in treatment response was found in mBC patients looking at HRs and CIs. Relevant, yet not statistically significant differences were found in the specific response of visceral metastases to modern combination therapies, especially in HER2-positive breast cancer: There was a benefit regarding OS using lapatinib combined with trastuzumab or trastuzumab and docetaxel combined with pertuzumab. Additionally, in two chemotherapy trials, there was a numerical difference between therapy response in visceral vs. non-visceral metastases regarding PFS in the unknown HER2 group, and regarding OS in the HER2 negative group.

Conclusions

In the subgroup analyses, we did not find any significant differences in response rates for visceral vs. non-visceral metastasis. There seems to be a beneficial effect of combination therapies regarding OS in visceral disease. At the present time, metastasis localization should not be used as a predictive marker for choice of systemic therapy in mBC.

Legal entity responsible for the study

Tahir Mehmood

Funding

None

Disclosure

All authors have declared no conflicts of interest.

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Breast cancer, metastatic Poster lunch Poster Display session

110P - Evaluation of eribulin and bevacizumab for the real world treatment of recurrent breast cancer (ID 1140)

Presentation Number
110P
Presentation Topic
Breast cancer, metastatic
Lecture Time
13:00 - 13:00
Speakers
  • M. Earashi
Authors
  • M. Earashi
  • K. Matsui
  • K. Maeda
  • W. Fukushima
  • K. Shimada
  • T. Shimizu
  • Z. Nozaki
  • Y. Tanada
  • K. Oyama
  • T. Nagata
  • A. Tsuneda
  • A. Yoshikawa
  • T. Yoshida
  • K. Kiyohara
  • K. Iwata
  • T. Ii
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

Recently several new chemotherapeutic agents have been developed and indicated for treatment of recurrent breast cancer. One of them, eribulin have improved overall survival (OS) in EMBRACE trials. On the other hand, bevacizumab has improved progression-free survival (PFS) in several clinical studies, but not extended OS in them. And there are few reports estimating these agents’ effects on OS and PFS of advanced or recurrent breast cancer patients in a real world setting.

Methods

Recurrent breast cancer patients who received chemotherapies in Toyama Breast Cancer Research Group (TBCRG) group institutes from January 2013 to March 2015 were reviewed. Kaplan-Meier method was utilized to estimate OS or PFS, and log-rank test was used to compare OS or PFS. Univariate and multivariate analyses were preformed to find significant factor(s) concerning OS.

Results

Of 208 patients who received chemotherapies in the period mentioned, there were 157 patients who received chemotherapies using both or either of eribulin (Eri), and bevacizumab (Bev). Median age of each group using Eri/Bev were 52.4/54.6. Disease status of Eri/Bev were as follows; 68.8%/79.0% ER positive, 18.8%/11.3% HER2 positive. Metastasis of each group using Eri/Bev were observed at; 51.0%/55.2% bones, 7.3%/8.1% CNS, 56.3%/47.2% lung, and 33.3%/49.6% liver. Response rates and PFS from the starting period of Eri/Bev were 21%/75%, and 387days/297days. Multivariate COX regression analysis disclosed negative HER2 status in Eri group, and liver involvement in Bev group influenced the response rates significantly. Earlier administration of Eri shows better survival durations from primary chemotherapies (1470 days), comparison with those of Bev (1076 days). Response rate/disease control rate of pre-line chemotherapies in Eri group were 32%/57%, and not significantly diffierent from 29%/65% in Bev group, but those of post-line chemotherapies were 21%/63% in Eri group and 6%/28% in Bev group.

Conclusions

According to our retrospective observation analyses of group data, eribulin did not reduce the effects of subsequent chemotherapies, and improved OS of advanced or recurrent breast cancer patients. We have to reassess the value of new chemotherapeutic agents continuously.

Disclosure

All authors have declared no conflicts of interest.

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Breast cancer, metastatic Poster lunch Poster Display session

111P - Changes in urinary NTX in early phase of denosumab therapy might be a predictive indicator in breast cancer patients with bone metastases (ID 1226)

Presentation Number
111P
Presentation Topic
Breast cancer, metastatic
Lecture Time
13:00 - 13:00
Speakers
  • M. Shizuku
Authors
  • M. Shizuku
  • Y. Mizuno
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

There are many reports suggesting that the levels of bone turnover markers (BTM) might be correlated with skeletal-related-events and disease progression in breast cancer patients with bone metastases (BM). We therefore evaluated the correlations OS with the changes in urinary N-telopeptide of type I collagen (u-NTX) in breast cancer patients with BM treated with denosumab (Dmab).

Methods

34 patients were enrolled in this study. All patients received Dmab 120 mg subcutaneously every month and u-NTX was checked at baseline and 1 month after Dmab was administered. We calculated the percentage change of u-NTX level (u-NTX%) [(baseline u-NTX level – 1-month u-NTX level)/baseline u-NTX level] and established a cut-off value by using receiver operating characteristic analysis. OS was defined as the time interval from Dmab administration to the date of death. The patients were divided into two groups by using the cut-off value, and OS was evaluated using the Kaplan-Meier method and analyzed by a log-rank test.

Results

According to the immunohistochemical analysis, estrogen receptor positive and human epidermal growth factor receptor 2 negative (ER+/HER2-) profile was observed in 22 patients, while ER+/HER2+, ER-/HER2+, and ER-/HER2- profiles were observed in 4, 2, and 6 patients, respectively. 2 patients had oligo-BM and 32 patients had multiple-BM. The mean u-NTX% was 0.63 and the established cut-off value was 0.669. The u-NTX% in 19 patients was >0.669 (high u-NTX group) while the remaining 15 patients had u-NTX% under 0.669 (low u-NTX group). OS in the high u-NTX group (n = 19) was significantly longer than in the low u-NTX group (n = 15) (24 months(M) vs 15 months(M), p = 0.005). In 22 ER+/HER2- patients, OS in the high u-NTX group (n = 12) was significantly longer than in the low group (n = 10) (34 M vs 16 M, p = 0.002). Moreover, in 20 patients without other organs metastases, OS in the high u-NTX group (n = 12) was significantly longer than in the low group (n = 8) (24 M vs 15 M, p < 0.001).

Conclusions

High u-NTX% in early phase of treatment could be a promising finding for OS in breast cancer patients with BM treated with Dmab.

Legal entity responsible for the study

Department of Breast Surgery, Yokkaichi Municipal Hospital

Funding

None

Disclosure

All authors have declared no conflicts of interest.

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Breast cancer, metastatic Poster lunch Poster Display session

112P - Phase II trial of metronomic combination chemotherapy with oral regimen in heavily pretreated metastatic breast cancer (ID 1241)

Presentation Number
112P
Presentation Topic
Breast cancer, metastatic
Lecture Time
13:00 - 13:00
Speakers
  • R. Prasanna
Authors
  • R. Prasanna
  • E. Prasad
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00
Breast cancer, metastatic Poster lunch Poster Display session

113P - Importance of immunohistochemistry for quick selection of breast cancer patients having BRCA1/2 mutations for their better treatment strategy: Pilot study in eastern India (ID 1971)

Presentation Number
113P
Presentation Topic
Breast cancer, metastatic
Lecture Time
13:00 - 13:00
Speakers
  • J. Basak
Authors
  • J. Basak
  • A. Chakraborty
  • A. Mukhopadhyay
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

In India, breast cancer is the second most common malignant condition among women. It is hereditary in 10% of cases, the majority related to mutations in the BRCA1 and BRCA2 genes. The presence of BRCA germline mutations in breast/ovarian carcinomas has been shown to have prognostic and therapeutic significance. Identification of tumours with BRCA defects has therapeutic and prognostic implications. Our objective was to assess whether immunohistochemical analysis (IHC) for BRCA is an effective method for the detection of BRCA dysfunction in hereditary breast carcinoma or not.

Methods

We have selected 231 patients for BRCA1/2 mutation detection during Aug.2010 to Oct.2015 from the breast cancer patients attended our hospital, NCRI. After taking written consent 4-5ml peripheral blood and/or operated tissue (where possible) were collected from BC patients. BRCA1/2 mutations were identified by ARMS-PCR, DNA sequencing and whole genome sequencing. We performed IHC staining with BRCA1 and BRCA2 antibody to distinguish tumour status between patients according to their indication of BRCA1 or BRCA2 mutation.

Results

Average age of the patients was 45.87±1.57 yrs. BRCA1/2 mutations were identified in 24 (10.38%) patientsthrough above mentioned methods. Tumour samples fromnine BRCA positive cases and 15BRCA negative cases were chosen for investigation of IHC. Out of 9 samples with BRCA mutations, 7were BRCA immunostainingnegative, with absence of nuclear or cytoplasmic staining. On the otherhand, from the 15 patients negative for mutations in both genes, 12 were positive for BRCA1immunostaining with a clear nuclear immunoreactivity in tumour cells. From ROCcurve analysis, it was found that IHC negativity (area- 0.211, CI: 0.011-0.411) isassociated (p = 0.02) with BRCA positivity.

Conclusions

In conclusion, we observed a high specificity for the prediction of BRCA1/2 carriers withimmunohistochemistry using BRCA antibody. Validation of this assay, using a larger sample, will allow using immunohistochemistry to decide which high-risk patients should be screenedfirst for the BRCA mutation gene.

Clinical trial identification

NA

Legal entity responsible for the study

Netaji Suibhas Chandra Bose Cancer Research Institue

Funding

None

Disclosure

All authors have declared no conflicts of interest.

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Immunotherapy of cancer Poster lunch Poster Display session

114P - Conquering cardiotoxicity of trastuzumab: A 99Tc radiolabelled bio-distribution study (ID 957)

Presentation Number
114P
Presentation Topic
Immunotherapy of cancer
Lecture Time
13:00 - 13:00
Speakers
  • A. Thakur
Authors
  • A. Thakur
  • V. Dhote
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

Overexpression of human epidermal growth factor receptor 2 (HER2) is responsible for approximately 35% of breast cancer cases. A number of approaches have been designed to inhibit overexpressed HER-2 receptors. Inhibiting these overexpressed HER-2 receptors in the breast is desirable. However, this inhibition never happens in isolation. HER-2 pathway in the heart, involved in the regulation of normal cellular metabolism, growth and survival, is also inhibited which leads to serious cardiotoxicity. The research was aimed to design a delivery system for trastuzumab which can bypass the cardiotoxicity without compromising the desired therapeutic action at the breast.

Methods

PEGylated liposomes of trastuzumab were formulated by lipid layer hydration technique. To ensure the maximum entrapment, different ratios of trastuzumab and lipids were utilised. The optimised formulation with maximum entrapment was labelled with 99 m Tc. In vivo biodistribution study was performed in rats xenografted with MCF-7 breast cancer cell lines to compare the biodistribution in heart and the breast tissues.

Results

Percent entrapment efficiency (%EE) of trastuzumab in liposomes was found to be 79.7% ± 8.2%. The labelling efficiency was almost the same up to 90 min after incubation for trastuzumab and liposomes. Less than 2% of radioactivity was dissociated after 6 hours incubation in the saline which indicates the suitability of the complex for its in vivo use. Results of biodistribution revealed that in the case of 99mTc-liposomes, the radioactivity present in the cancerous breast was greater at all timepoints compared to that in the heart

Conclusions

PEGylated liposomes seem to be a promising delivery system to overcome the cardiomyopathy associated with trastuzumab. Pegylated lipid system spends less time in the heart due to lymphatic drainage. And whatever time it spends in the heart, it is shielded by the lipid barrier.

Legal entity responsible for the study

VNS Institutional Ethical Committee

Funding

None

Disclosure

All authors have declared no conflicts of interest.

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Breast cancer, metastatic Poster lunch Poster Display session

115P - Triple negative breast cancer: Survival and age at time of diagnosis among the Lebanese population (ID 811)

Presentation Number
115P
Presentation Topic
Breast cancer, metastatic
Lecture Time
13:00 - 13:00
Speakers
  • C. Kassab
Authors
  • C. Kassab
  • F. Nasr
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

Invasive triple-negative breast cancer accounts for 10-20% of breast cancers and is responsible for a high percentage of breast cancer-related deaths. It is indeed a very aggressive tumor that is associated with a poor prognosis with high risk of relapse and a short disease-free survival. It is treated by chemotherapy only and does not benefit from targeted therapy until now. The purpose of this study was to analyze progression-free survival (PFS) and overall survival (OS) after the change of therapeutic modalities, and the age at diagnosis of triple-negative breast cancer in Lebanese women and to compare the age distribution with a preceding Lebanese study and a recent American study of 38,813 patients nationwide.

Methods

Data were collected from hospitals and pathology laboratories across Lebanon. The collection was based on the following inclusion criteria: female diagnosed with an invasive TNBC between 2010 and 2016. PFS was studied in 193 cases, the overall survival analysis was done on 63 cases and the age at time of diagnosis on 387 cases. The statistical analysis was done using Student t tests.

Results

PFS improved from 19 to 35 months after the change of therapeutic protocols and the OS increased from 19 to 23 months (p < 0.001). The average age at time of diagnosis was approximately 56 years, compared with 52 years in the previous Lebanese study and there was a clear age disparity of the age at time of diagnosis between and Lebanese and American study when comparing patients of identical age groups. The age at diagnosis does not depend on the geographical area.

Conclusions

The new therapeutic protocols proved to be more effective, but screening programs must be done at an earlier age. The findings may be pertinent for the Lebanese patients and warrant further evaluation in different ethnic groups and populations.

Clinical trial identification

NA

Legal entity responsible for the study

Holy Spirit University of Kaslik

Funding

None

Disclosure

All authors have declared no conflicts of interest.

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Breast cancer, metastatic Poster lunch Poster Display session

116P - Real world data on use of palbociclib in hormone-receptor (ER) positive HER2 negative metastatic breast cancer (MBC) among Asian patients (ID 1871)

Presentation Number
116P
Presentation Topic
Breast cancer, metastatic
Lecture Time
13:00 - 13:00
Speakers
  • J. Chiu
Authors
  • J. Chiu
  • R. Leung
  • H. Sze
  • P. Teo
  • P. Choi
  • T. Lam
  • T. Yau
  • P. Cheng
  • F. Cheung
  • P. Cheung
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

Palbociclib has been approved by the US FDA since 2015 yet safety and efficacy data among Asian patients is limited. This study reports the use of this drug in ER-positive HER2-negative MBC in Hong Kong as real world practice.

Methods

The demographic data, treatment response, and toxicity profile of patients received palbociclib were collected in a prospectively maintained database. Patients were from both the public and private sectors. The study is supported by the Hong Kong Breast Cancer Foundation.

Results

Fifty-four patients who have received palbociclib for the first time were recruited in the database. The median age was 51 year (range 34-81) and all patients were ethnic Chinese. All were post-menopausal by natural state (67%) or by ovarian suppression. Over half (55%) obtained palbociclib from the name-patient program prior to the launch of the drug in Hong Kong in Jan 2017. The proportion of first line use was 30% prior to- and 36% after the official launch of palbociclib. The partner endocrine therapy (ET) was aromatase inhibitor (39% letrozole, 11% exemestane) or fulvestrant (50%). Except for 4 patients, the majority (93%) were started on the standard dose of 125 mg/day. Of those started on 125 mg/day, 43% developed Gd 3 neutropenia, and 7% had Gd 4 neutropenia during the first cycle; 31% had dose reduction to 100 mg/day on second cycle. Other adverse events (AEs) included anemia (4%), thrombocytopenia (9%), stomatitis (5%), hand-foot syndrome (4%), fatigue (4%), and low appetite (4%). All these were Gd 1-2. No patient had neutropenic fever. Response assessment was available in 37 cases. The disease control rate was 70%. Many responded patients had visceral disease (54%) and were heavily pretreated (chemotherapy 1 line 15%, > =2 lines 35%; ET > =2 lines 27%; mTOR inhibitor 12%).

Conclusions

This is the first real world data reporting the preliminary efficacy and AEs of palbociclib among ER-positive HER2-negative MBC patients from Hong Kong. Palbociclib was well tolerated. The experience is consistent with published literature of Palbociclib. The use of palbociclib in Hong Kong is often in the second or later line setting and the cause remains to be elucidated.

Clinical trial identification

Not applicable

Legal entity responsible for the study

N/A

Funding

Pfizer

Disclosure

All authors have declared no conflicts of interest.

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Breast cancer, metastatic Poster lunch Poster Display session

117P - The role of ELF3 in metastasis of triple negative breast cancer (ID 1256)

Presentation Number
117P
Presentation Topic
Breast cancer, metastatic
Lecture Time
13:00 - 13:00
Speakers
  • S. Park
Authors
  • S. Park
  • Y. Kwon
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

Triple negative breast cancer (TNBC) is categorized by a lack in estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor 2 receptor (HER2). TNBC is known to be more aggressive and lethal than other types of breast cancer because of their highly invasive and migratory ability. However, the mechanisms and main contributors of their metastatic ability are still unclear. ETS transcription factors are related with tumorigenesis in many tissues including breast epithelium. Among them, ELF3 (ESX/ESE1) is an epithelial-specific gene that is specifically associated with breast cancer and has been amplified in early breast cancer. The potential role of ELF3 in cytoplasm is presented, but the mechanism of ability to regulate tumor-associated gene expression and breast cell survival for ELF3 are not yet known. Several studies have suggested that the role of EMT is important in the aggressiveness and metastasis of TNBC. It is also known to play an important role in the formation of tumors in most invasive cancer. The main functions of EMT, such as down-regulation of E-cadherin and up-regulation of MMP, are known to be regulated by transcription factors including Snail, Slug and ZEB1.

Methods

For investigation of ELF3 ability in TNBC, we performed a series of assays; western blot, wound healing, invasion, soft-agar colony formation, flow cytometry, anoikis, CAM and immunofluorescence assays.

Results

In this study, we found that ELF3, an ETS transcription factor, was expressed low and high in mesenchymal and epithelial type of TNBC cell lines, respectively. Remarkably, overexpressed ELF3 in the highly invasive TNBC cell lines, MDA-MB-231 and BT549, suppressed EMT by attenuating the expression of several EMT-associated proteins (Vimentin, Slug and MMPs). Moreover, ELF3 overexpression reduced the tumor growth of BT549 in chick embryo chorioallantoic membrane (CAM) model.

Conclusions

Although high ELF3 expression has been known to be associated with tumorigenesis of other breast cancer types, overexpression of ELF3 in TNBC suppressed the metastatic potential of invasive TNBC cells. Our results suggest the important role for ELF3 in metastasis of TNBC.

Legal entity responsible for the study

Ewha Womans University

Funding

None

Disclosure

All authors have declared no conflicts of interest.

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CNS tumours Poster lunch Poster Display session

120P - Glioblastoma multiforme overcomes ultrasmall superparamagnetic iron oxide nanoparticle induced cytotoxicity through heat shock protein protective mechanisms (ID 878)

Presentation Number
120P
Presentation Topic
CNS tumours
Lecture Time
13:00 - 13:00
Speakers
  • T. Pang
Authors
  • T. Pang
  • G. Fatseas
  • M. Koina
  • S. Adamson
  • S. Wilkinson
  • T. Chan-Ling
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

Glioblastoma Multiforme (GBM) is an aggressive brain cancer associated with high mortality. Current treatments including resection of 98% or more of the tumour result in median survival of less than 15 months. With such poor outcomes, innovative therapies are required. Ultrasmall Superparamagnetic Iron Oxide Nanoparticles (USPIONs) are emerging as potential treatments, however little is known on their effects on cells. Understanding interactions between USPIONs and GBM is critical in developing these therapies. The aim of this study is to investigate biological effects of USPION uptake on GBM cells in vitro.

Methods

CNS-1 cell cultures were exposed to 20µg/mL of USPIONs with a maghemite iron oxide cores, which mean core diameters are 10–15 nm. In order to measure the intake and the interaction of USPIONs on CNS-1, we have utilized different techniques including the transmission electron microscopy (TEM), iron quantification, mitochondrial membrane potential assay, Oxidative Stress Test, Mitochondrial Transition Pore Assay, flow cytometry, immunohistochemistry and western blotting.

Results

Our results showed that USPIONs entered CNS-1 cells via clatherin coated pits which then became internalized in vacuoles. USPIONs induced Fenton Reaction, which potentially leads to the oxidative stress activating the Heat Shock Proteins (HSPs) protective mechanism. When this mechanism was overwhelmed, it led to a decrease in cell viability, however in due course, cells upregulated HSPs, re-activating these protective mechanisms which included the closure of mitochondrial permeability transition pore, limiting the release of pro-apoptotic cytochrome c, reducing oxidative stress and eventually recovering cell viability.

Conclusions

Ultrasmall superparamagnetic iron oxide nanoparticles interact with CNS-1, initiating the mitochondrial death pathway, however heat shock proteins are recruited, mitigating further apoptosis. Targeting CNS-1 protective mechanisms in conjunction with USPIONs exposure could induce a cytotoxic effect on CNS-1, providing insights for a novel therapy for this devastating disease.

Legal entity responsible for the study

Tailoi Chan-Ling

Funding

None

Disclosure

All authors have declared no conflicts of interest.

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CNS tumours Poster lunch Poster Display session

121P - SIRT1 inhibition exhibits decreased pluripotency in cancer stem cells of glioma (ID 1257)

Presentation Number
121P
Presentation Topic
CNS tumours
Lecture Time
13:00 - 13:00
Speakers
  • M. Bhagat
Authors
  • M. Bhagat
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

SIRT1, a class III histone deacetylase has cancer relevance because it regulates lifespan in multiple organisms and down-regulates p53 function through deacetylation. Cancer Stem Cells are a small subset of cells that are responsible for initiation, development, and recurrence of tumors. Therefore, it is important to understand the molecular mechanism of Cancer Stem Cells for translational applications in the treatment of patients with cancer. Role of SIRT1 in enhancing tumorigenesis has been well documented in many cancers. However, its functional role in glioma cancer stem cells is largely unknown.

Methods

In order to comprehend the role of SIRT1 in glioma cancer stem cells, we used EX-527, a nanomolar inhibitor of SIRT1 in three glioma Grade IV cell lines –U87MG, A172 and LN229. This was followed by expression analysis by Q-PCR, Immunofluorescence and Tumor sphere assay in glioma and cancer stem cells of glioma. Cell proliferation was assessed by XTT. Expression of genes in 20 grade IV glioma patient samples was compared to normal brain sample.

Results

U87MG, A172 and LN229 cells cultured in Stem Media exhibited an increase in SIRT1 expression compared to Normal media. XTT assay after EX527 treatment (10nM to 100µM) did not exhibit any change in cell proliferation compared to control cells in all the three glioma cell lines. SIRT1 inhibition exhibited a decreased expression of stemness markers –Sox-2 and Oct-4 and a decreased capacity to form gliomaspheres compared to the Control cells. Finally, we have correlated our in-vitro results with human GBM samples and found that SIRT1 and stemness markers correlated well in native tumor samples.

Conclusions

The results indicate a role of SIRT1 as a pluripotent marker in cancer stem cells of glioma. SIRT1 deacetylates p53 rendering it inactive and thus initaiting a ascade of events with oncogenic potential. Cancer stem cells are the cells responsible for drug resistance and tumor relapse Thus knowing the mechanism of SIRT1 action in cancer stem cells would open doors for more target specific therapy. Our study provides a functional interaction of SIRT1 with the stemness markers in cancer stem cells of glioma and glioma patient samples thus aiming for target specific approaches in glioma.

Legal entity responsible for the study

All India institute of Medical Sciences

Funding

Indian Council of Medical Research

Funding

Indian Council of Medical Research

Disclosure

The author has declared no conflicts of interest.

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CNS tumours Poster lunch Poster Display session

122P - Stereotactic radiosurgery in combination with high-dose methotrexate in the treatment of primary central nervous system lymphoma (ID 1374)

Presentation Number
122P
Presentation Topic
CNS tumours
Lecture Time
13:00 - 13:00
Speakers
  • H. Long
Authors
  • H. Long
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

Primary central nervous system lymphoma (PCNSL) is a rare cancer accounting for less than 3% of primary brain and central nervous system (CNS) tumors. Tissues involved include the brain parenchyma, leptomeninges, eyes, and spinal cord. High-dose methotrexate (HD-MTX) is the gold standard for newly diagnosed PCNSL. However, the efficacy of stereotactic radiosurgery (SRS) instead of whole brain radiotherapy following HD-MTX for PCNSL is unclear. The purpose of this study is to determine the effectiveness of HD-MTX in combination with SRS in the treatment of PCNSL.

Methods

This is a retrospective, observational cohort study evaluating the treatment of histologically confirmed PCNSL with HD-MTX as a single agent in a dose of 3.5 g/m2 (control) and treatment with MTX plus SRS. Strict inclusion and exclusion criteria were employed. Primary outcomes were measured by overall survival. Secondary outcomes were assessed by the tumor’s responsiveness to treatment and reduction in size as noted on imaging, the Karnofsky Performance Status (KPS), the activities of daily living (ADL) and mini-mental state examination (MMSE).

Results

Between January 2008 and January 2013, 68 cases were evaluated. Included in this evaluation were 42 chemotherapy and 26 chemotherapy, plus SRS. The follow-up period was 24 to 50 months (mean: 32.8 months). There were no statistically significant differences in patient demographics or histology diagnosis. Patients were treated with SRS doses ranging from 11 Gy to 16 Gy (mean: 13 Gy). The median survival rate from initial diagnosis was 28.6 months in the chemotherapy group and 48.6 in the chemotherapy, plus SRS, group (p-value: 0.0051). No significant side effects related to SRS were observed. During follow-up period, the good ADL preservation was achieved for 16 months from SRS. Patients with KPS >90 at SRS demonstrated longer ADL preservation (36 months from SRS). No significant difference in MMSE between two groups were found.

Conclusions

SRS in combination with high-dose methotrexate provided better prognosis and not worse neurocognition state. This noninvasive treatment modality should be considered as an option for patients with PCNSL, but should be validated in a large patient population.

Legal entity responsible for the study

Nanfang Hospital, Southern Medical University, Guangzhou, China

Funding: None

Disclosure: The author has declared no conflicts of interest.

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CNS tumours Poster lunch Poster Display session

123P - Curcumin downregulates FAT1 expression via NFkB in glioblastoma (ID 1716)

Presentation Number
123P
Presentation Topic
CNS tumours
Lecture Time
13:00 - 13:00
Speakers
  • C. Srivastava
Authors
  • C. Srivastava
  • Y. Gupta
  • K. Irshad
  • P. Chattopadhaya
  • C. Sarkar
  • A. Suri
  • S. Sinha
  • K. Chosdol
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

Glioblastoma (GBM) is the most aggressive brain cancer. Curcumin, a natural dietary polyphenol extracted from Curcuma longa L, has a demonstrated promising outcome against the GBM. Many molecular targets of curcumin are still undefined. Our lab is focused on the functional role of FAT1 which is a transmembrane protein and found to have oncogenic role in GBM. This study is designed to analyze the regulation of FAT1 expression by curcumin.

Methods

U87MG cells were treated with Curcumin (5uM, 10uM and 20uM) for 24 hours, PDTC (Pyrrolidine dithiocarbamate) (5uM and 10uM) for 1 hour and TNFα (100ng/ml) for 24 hours. FAT1 promoter pGL3F1 [1kb; -200bp/+848bp from transcription start site (TSS) (+1)] was cloned in luciferase vector (pGL3Basic) and promoter activity was analysed in U87MG, A172, and U373MG. Characterization of NFkB binding sites was done by FAT1 deletion constructs (5’ and 3’ NFkB site deletion), site directed mutagenesis (SDM) and ChIP assay. FAT1 and NFkB expression were correlated in GBM tumors (n = 16) and TCGA GBM data set.

Results

FAT1 and NFkB was significantly downregulated in U87MG cells treated with curcumin. Also, PDTC (NFkB inhibitor) treatment showed significant decrease in FAT1 expression. But, TNFα (NFkB stimulator) treatment showed increased FAT1 expression in U87MG cells. Transfac (in-silico) analysis predicted three NFkB sites at -90bp/-80bp, +347bp/+356bp and +360bp/+368bp on 1kb FAT1 promoter. Glioma cell lines were transfected with cloned FAT1 promoter constrcut (pGL3F1), showed significant increase in promoter activity. Interestingly, FAT1 promoter activity was downregulated in curcumin treated cells and upregulated in TNFα treated cells. The most potential binding site for NFkB was found to be at-90bp/-80bp on FAT1 promoter upstream to TSS (+1). In our inhouse GBM tumors (n = 16), increased expression and a positive correlation between FAT1 and NFkB (r = 0.70, p < 0.01) was observed, which was also corroborated in TCGA GBM data set.

Conclusions

Our in-vitro and GBM tumor analysis for the first time confirms the regulation of FAT1 by curcumin via NFkB transcription factor in glioblastoma and also validating a novel link between NFkB and FAT1.

Legal entity responsible for the study

AIIMS

Funding

Indian council for medical research (ICMR)

Disclosure

All authors have declared no conflicts of interest.

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CNS tumours Poster lunch Poster Display session

124P - FAT1 on Salvador-Warts-Hippo (SWH) pathway in human Glioblastoma (ID 2034)

Presentation Number
124P
Presentation Topic
CNS tumours
Lecture Time
13:00 - 13:00
Speakers
  • Y. Gupta
Authors
  • Y. Gupta
  • S. Shivajirao
  • K. Irshad
  • B. Dikshit
  • T. Srivastav
  • P. Chattopadhyay
  • S. Sinha
  • K. Chosdol
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00
CNS tumours Poster lunch Poster Display session

125P - Impact of the time to initiation of chemoradiation on outcome of glioblastoma (ID 919)

Presentation Number
125P
Presentation Topic
CNS tumours
Lecture Time
13:00 - 13:00
Speakers
  • A. Al Alhumiqani
Authors
  • A. Al Alhumiqani
  • A. Altwairgi
  • B. Basulaiman
  • A. Balbaid
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

Glioblastoma multiforme (GBM) is the most common, malignant primary brain tumor. Surgical resection followed by concurrent Chemoradiation (CCRT) and adjuvant chemotherapy is the standard treatment at this time. Unlike other tumors, the impact of the time to initiation of CCRT on outcome remains unclear. The aim of this analysis was to investigate the impact of time to initiation of CCRT on outcome in patients with GBM treated at King Fahad Medical City (KFMC), Saudi Arabia.

Methods

All adult patients treated with CCRT at KFMC from January 2008 until June 2016 were included. A data collection form was developed to collect patient demographics, pathology, radiotherapy and chemotherapy details, progression and survival outcomes. The interval to initiation of CCRT was determined from the time of surgical intervention. The impact of the time to initiation of CCRT on overall (OS) and progression-free (PFS) survival was evaluated by univariate Log-rank tests and multivariate Cox-regression analysis.

Results

In this analysis, 100 patients treated with CCRT were included. Median age was 49 (18-81). 72% of included patients were male, and 89% underwent resection. The majority of patients, 79% received adjuvant Temozolomide (TMZ) with a median of 4 cycles. The median of time to initiation of CCRT was 5.1 weeks (1.4 to 12.8) with 33% of patient were started on CCRT beyond six weeks of surgery. In univariate and multivariate analyses, time to initiation of CCRT have no significant impact on either PFS (univariate, p = 0.81, multivariate, p = 0.96) or OS (univariate, p = 0.44, multivariate, p = 0.43). On multivariate analysis, the better survival rate was seen in patients received adjuvant TMZ (P = 0.001) and worse survival rates were associated with ECOG >2 (P = 0.009), the presence of comorbidities (P = 0.04) and residual disease (P = 0.004).

Conclusions

In this single-center retrospective study, no significant impact of the time to initiation of CCRT was demonstrated on the outcome of GBM patients. Prospective studies are needed to define the optimal timing of CCRT after surgical resection in GBM.

Legal entity responsible for the study

Ethical Committee- King Fahad Medical City -Riyadh -Saudi Arabia

Funding: None

Disclosure: All authors have declared no conflicts of interest.

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CNS tumours Poster lunch Poster Display session

126P - Gamma knife radiosurgery for treatment of cavernous sinus meningioma patients in Tangerang, Indonesia: A preliminary study (ID 1906)

Presentation Number
126P
Presentation Topic
CNS tumours
Lecture Time
13:00 - 13:00
Speakers
  • P. Wibisono
Authors
  • A. Vatvani
  • P. Wibisono
  • S. Evangelina
  • A. Widjaja
  • E. Soediatmoko
  • I. Hasbiullah
  • L. Hendriansyah
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

Despite the advancement of microsurgery and other skull base techniques, complete resection of skull base meningiomas still remains a challenge for neurosurgeons. The tumor in cavernous sinus meningioma is deep seated and total resection using open microsurgery can lead to various complications. The mortality and morbidity rates caused by total resection using open neurosurgery is still high. Over the past decade, there were many reports regarding the recurrence and progression rate of microsurgically treated cavernous sinus meningiomas. Gamma knife is an alternative which provides a more accurate and safer way of treating meningiomas. The aim of this study is to evaluate the tumor size and clinical symptoms in cavernous sinus meningioma patients after gamma knife radiosurgery.

Methods

This is a retrospective study that took place in Gamma Knife Centre Indonesia. We evaluated patients’ clinical characteristics and tumor size pre and post gamma knife radiosurgery from 2012 to 2015. The data is presented in the form of descriptive statistics.

Results

There was a total of 25 patients with skull base meningiomas, out of which 9 of them were located in the cavernous sinus area. There were 6 female and 3 male patients. The mean age of the patients was 50.6 (36-70) years. The mean follow-up time post-radiosurgery was 6.67 (4-12) months. The mean tumor volume before radiosurgery was 12.36 (1.51-34.45) cm3. The mean tumor volume after radiosurgery was 10.19 (0.98-28.80) cm3. The dose used was between 12 to 18 gray. Post-radiosurgery, clinical symptoms such as hypesthesia improved in 1 out of 2 patients (50%), seizures improved in 100% of patients, blurred vision improved in 2 out of 4 patients (50%), cranial nerve III, IV and VI function improved in 2 out of 4 patients (50%), headaches was no longer present in 50% patients and double vision improved in 100% of patients.

Conclusions

Gamma knife radiosurgery reduces the tumor size and improves the clinical symptoms in patients with cavernous sinus meningiomas. However, large prospective studies should be done in order to further evaluate the long term effects of gamma knife for skull base meningiomas.

Legal entity responsible for the study

Faculty of Medicine, Pelita Harapan University

Funding

None

Disclosure

All authors have declared no conflicts of interest.

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CNS tumours Poster lunch Poster Display session

127P - Apatinib combined with irinotecan in treatment of recurrent high-grade gliomas (ID 2067)

Presentation Number
127P
Presentation Topic
CNS tumours
Lecture Time
13:00 - 13:00
Speakers
  • X. Jiang
Authors
  • L. Wang
  • T. Yang
  • Y. Xia
  • Y. Qiao
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

High-grade gliomas (HGGs) are the most common and aggressive group of primary central nervous system (CNS) tumors. They are characterized by diffuse parenchymal infiltration and prominent angiogenesis. Apatinib is a novel inhibitor of VEGFR-2, which was admitted for the treatment of advanced gastric cancer patients who had failed after the second-line and above treatment. However, there have been no reports for treating recurrent high-grade gliomas with this drug.

Methods

This was a single-arm, open-label, exploratory study design. Eligibility criteria included histologically proven glioma, patient age 18-75 years. A history of receiving previous treatment was not required. All the patients were orally given apatinib at an initial dose of 500-850 mg (qd) and irinotecan (125 mg/m2) on days 1, 8 of each 21-day cycle. After 6 cycles, patients were treated with apatinib 500-850 mg (qd) until disease progression or death.

Results

A total of 10 patients including 7 males and 3 females were eligible. The median age was 49 years (range 27-66 years). Among the 10 patients, 9 were available for the efficacy evaluation. Two patients achieved partial response (PR), 3 had stable disease (SD), and 4 had progressive disease (PD). The objective response rate (ORR) and the disease control rate (DCR) were 22.22% (2/9) and 55.56% (5/9), respectively. All patients were included for safety analysis. The incidence of adverse events (AEs) was 100%. The common AEs were bone marrow suppression (50%) and hypertension (40%), gastrointestinal reaction (30%), diarrhoea (30%) and sinus rhythm (20%).

Conclusions

Apatinib combined with irinotecan is an active regimen for patients with recurrent high-grade gliomas with a comparable disease control and tolerable adverse reactions.

Clinical trial identification

None

Legal entity responsible for the study

N/A

Funding

None

Disclosure

All authors have declared no conflicts of interest.

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CNS tumours Poster lunch Poster Display session

128P - Is fotemustine a good option after irinotecan-bevacizumab in high-grade glioma? (ID 785)

Presentation Number
128P
Presentation Topic
CNS tumours
Lecture Time
13:00 - 13:00
Speakers
  • P. Ramirez Daffós
Authors
  • P. Ramirez Daffós
  • M. Martinez Bautista
  • G. Blanco Sanchez(
  • S. Estalella
  • J. Baena Cañada
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

Recurrent high-grade glioma (GAG), don't usually benefit from a second surgery or reirradiation. With the addition of bevacizumab or fotemustine (FTM), the median OS is 9.2 and 8 months, respectively. There is no currently clinical trial showing a 3rd line treatment benefit in recurrent GAG. The aim of this study is to describe the clinical experience in our hospital with FTM in 3rd line.

Methods

An observational, retrospective study was conducted. All patients had progressed to temozolomide and irinotecan+bevacizumab and had received at least one cycle of fotemustine (FTM) from 2010 to the present. The schedule was: induction doses with 80 mg/m2 intravenously on days 1–15–30–45–60 and maintenance with 80 mg/m2 every 3 weeks.

Results

7 patients were included, 5 women, median age 41 years, 42% (n = 3) were anaplastic astrocytomas and 58% (n = 4) multiform glioblastoma, 100% of the patients had PS 0–1. To date, 6 of the 7 patients had progressed, with a median PFS of 1 month. The 3- month survival rate was 71.42%, and the median OS (5/7 deceased patients) was 3.3 months. No adverse events of grade ≥3 were reported.

Conclusions

Fotemustine in third line treatment of GAG shows moderate effectiveness but is a well tolerated treatment, so it could be considered in the third line in patients with GAG with good functional status.

Legal entity responsible for the study

Patricia Ramirez

Funding: None

Disclosure: All authors have declared no conflicts of interest.

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CNS tumours Poster lunch Poster Display session

129P - Outcomes and prognostic factors in re-irradiation of intracranial gliomas: Single institution experience (ID 1144)

Presentation Number
129P
Presentation Topic
CNS tumours
Lecture Time
13:00 - 13:00
Speakers
  • S. Paul
Authors
  • S. Paul
  • N. Sesikeran
  • V. Reddy
  • K. Bhattacharyya
  • S. Ahmed
  • R. Patlola
  • P. Upadhyay
  • V. Reddy
  • K. Mohanti
  • S. Reddy
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

The treatment options for recurrent gliomas are limited. Re-irradiation is being increasingly considered as an option, in view of the advances in treatment techniques, the ability to document doses and overlay plans. However, there is lack of data on outcomes, cumulative doses and prognostic factors in re-irradiation of gliomas. This study attempts to collate a single institutions’ data on re-irradiation of gliomas.

Methods

This is a retrospective analysis of outcomes and prognostic factors in re-irradiation of intracranial gliomas. All patients of gliomas who received re-irradiation between January 2012 to January 2017 were included. Medical records were evaluated to collect data on outcomes of 22 patients treated in a single institution. Survival curve was estimated using Kaplan maier method. Pearsons correlation co-efficient was used to identify factors correlating with better survival.

Results

Median age of patients undergoing re-irradiation was 45yrs (8-66yrs), of which 59% were female, 41% male. The histopathological diagnosis at initial radiation was predominantly grade2 (50%) and grade 3 (31.8%), only 18.1% were glioblastomas. However, at the time of re-irradiation, most common diagnosis was grade 3 glioma (40.9%). Glioblastomas were 36.3%, grade 2 gliomas were 18.1% and 4.5% did not undergo biopsy or surgery at recurrence. Median cumulative dose in 2Gy equivalent – NTD (Normalized Total Dose) was 108Gy (94Gy – 120Gy). Re-irradiation was delivered at standard fractionation in all except one patient, who received hypofractionated dose of 3.5Gy per fraction. Median time interval between the two courses of radiation was 38 months (12-360 months). All patients received IMRT, image guidance. Median re-irradiation volume was 405cc. ROC curve was generated, which showed thatcummulative dose of 115Gy and above was associated with better survival. There were no reported cases of symptomatic brainnecrosis. Median survival was 24 months following re-irradiation. Among the various prognostic factors tested, tumor volume at the time of re-irradiation was the only factor which correlated with survival.

Conclusions

Re-irradiation of gliomas should be considered a valid option in select cases, particularly in small volume recurrences. IMRT with image guidance with conventional fractionation upto total cumulative dose of 115Gy can be considered safe.

Legal entity responsible for the study

Department of Radiation Oncology, Apollo Cancer Institute, Hyderabad

Funding

None

Disclosure

All authors have declared no conflicts of interest.

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CNS tumours Poster lunch Poster Display session

130P - Biomarker prevalence in high grade glioma patients from Siloam Hospital Karawaci Indonesia (ID 858)

Presentation Number
130P
Presentation Topic
CNS tumours
Lecture Time
13:00 - 13:00
Speakers
  • G. Prayogi
Authors
  • G. Prayogi
  • Z. Wuisan
  • D. Budiharko
  • T. Putra
  • N. Masykura
  • P. Prasetiyo
  • J. July
  • E. Wahjoepramono
  • A. Utomo
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

High Grade Gliomas (HGG) are most common types of primary brain tumor, characterized by poor prognosis and immune evasion properties. Molecular profiling of HGG patients may help clinicians in developing therapeutic strategies. However, molecular profiles of Indonesian patients are rarely studied. We investigated the prevalence of O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation and Isocitrate Dehydrogenase (IDH) mutation as a primary prognostic biomarkers for chemotherapy, as well as Epidermal Growth Factor Receptor (EGFR) and Tumor Protein 53 (TP53) Expressions to describe HGG molecular properties in indonesian patient cohort.

Methods

FFPE tumor samples from Siloam hospital (N = 43 patients) were analyzed using methylation Specific PCR, High Resolution melting PCR, and Direct sequencing to identify methylation of MGMT promoter and mutation of IDH gene. Immunohistochemistry staining methods were performed to analyze expressions of EGFR and TP53 proteins. Statistic analysis were used to describe its association with age groups and histological classification [Glioblastoma Multiforme (GBM) vs (Non-GBM) HGG].

Results

Four samples were discarded from analysis due to lack of viable tumor cells. GBM cases made up 64% of total sample (25/39) with median age 53 years old. The MGMT methylation rate was 36% (9/25) and more frequent in non-GBM groups (31% vs 44%; GBM vs non-GBM respectively). IDH1 mutation (R132H) were detected in 15% patient (6/39) and significantly related with non-GBM case (p = 0.0163). TP53 and EGFR protein expressions were detected in 73.6% (28/38) and 34% (13/38) of sample respectively. TP53 expressions were found frequently in non-GBM patients, whereas EGFR was most common in GBM patients. Overall survival analyses showed patients with overexpressed p53 proteins had good prognosis (p = 0.012).

Conclusions

Our retrospective study revealed the MGMT promoter methylation (36%) and IDH mutation rates (15%) and patterns were consistent to common features of HGG. Moreover, frequent p53 expression in our non GBM cohort was consistent with secondary nature of HGG and was associated with good prognosis. Our study may help improving treatment strategy based on distinct biomolecular characteristics.

Legal entity responsible for the study

Institutional Review Board, Stemcell And Cancer Institute, PT. Kalbe Farma TBK

Funding

PT. Kalbe Farma, Tbk

Funding

PT. Kalbe Farma, Tbk

Disclosure

All authors have declared no conflicts of interest.

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CNS tumours Poster lunch Poster Display session

131P - Role of chromosomal 1p/19q co-deletion on the prognosis of oligodendrogliomas in Pakistan (ID 1660)

Presentation Number
131P
Presentation Topic
CNS tumours
Lecture Time
13:00 - 13:00
Speakers
  • M. Tariq
Authors
  • Z. Ahmed
  • M. Tariq
  • T. Moatter
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

1p/19q co-deletion is a pathognomonic biomarker that defines a distinct glioma entity and is characteristic of oligodendrogliomas. The presence of 1p/19q co-deletion is a strong independent prognostic biomarker associated with improved survival in both diffuse low-grade and anaplastic tumours.1p/19q-co-deletion has predictive value for response to chemotherapy in anaplastic oligodendrogliomas. FISH is unable to differentiate between the whole chromosome arm deletions with centromeric breakpoints characteristic of 1p/19q co-deleted oligodendrogliomas, from smaller focal deletions. This distinction is important given the association of 1p/19q whole-arm co-deletion with improved survival and response to chemotherapy in the oligodendroglial tumour subtype.

Methods

FISH probes targeting 1p and 19q regions were used to determine deletion status of oligodendrogliomas patients having grades II or III disease. FISH was performed on 4 μm thick tissue sections using Abbott Molecular (USA) dual color probe sets [LSI 1p36/LSI 1q25 and LSI 19p13/LSI 19q13] according to the manufacturer’s instructions. A total of 60 nuclei were examined. The ratio was calculated for 1p and 19q deletion by dividing 1p or 19q signals by their respective control signals; <0.8 was considered as abnormal for both targets.

Results

This study investigated 99 patients of oligodendroglioma enrolled between 2013 and 2016 at the Aga Khan University Hospital. 2016. The male to female ratio was 2:1. Mean age was 39 years and patients’ ages ranged from 13 to 79 years. Thirty-five (35%) cases demonstrated co-deletion of 1p/19q, 2 cases showed isolated 1p deletion, whereas 19q deletion was positive in 9 patients. Among patients exhibiting 1p/19q co-deletion, 17 cases (48.5%) were grade II tumors and 16 cases (45.7%) were grade III tumors. Two (5.7%) of the cases had features intermediate between grade II and III.

Conclusions

On the basis of our findings, patients with 1p/19q-co-deleted anaplastic oligodendroglial tumours should not be treated with radiotherapy alone, but instead receive early alkylating chemotherapy with radiotherapy. A similar approach should be considered in a subset of patients with grade II oligodendroglioma.

Legal entity responsible for the study

Aga Khan Hospital

Funding

None

Funding

None

Disclosure

All authors have declared no conflicts of interest.

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CNS tumours Poster lunch Poster Display session

132P - Formalin fixed and paraffin embedded tissue samples: Potential valuable resource for molecular analysis in medical research (ID 1182)

Presentation Number
132P
Presentation Topic
CNS tumours
Lecture Time
13:00 - 13:00
Speakers
  • R. Narayanappa
Authors
  • R. Narayanappa
  • M. Aithal
  • P. Rout
  • A. Chand
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

FFPE tissue repertoires with patient clinical data have been gathered for decades, presenting a valuable resource for retrospective studies. Since long term storage and access of fresh tissues have many challenges, development of archives of formalin fixed and paraffin embedded (FFPE) sections are widely adopted. FFPE tissues are routinely used world-wide for histopathological diagnosis of various diseases. We have attempted to carry out gene expression analysis and DNA methylation profiles on FFPE tissue samples in patients with lymphomas and glioblastomas to understand the molecular basis of the disease and to identify molecular biomarkers.

Methods

Immunohistochemistry and FISH were carried out on tissue microarrays (TMA). Methylation specific PCR was carried on the same tissue sections. Gene expression analysis was also done on glioblastoma FFPE tissue sections.

Results

Comparable results were obtained on lymphomas and glioblastoma FFPE tissue sections.

Conclusions

With growing interest in understanding the molecular basis of any disease, FFPE samples represent a valuable resource since follow-up clinical data and disease prognosis are often collected years after the specimen collection. Furthermore, data from FFPE tissue based assays not only complement disease diagnosis but also allow designing of personalized therapeutic regimens. However, other tissue types also need to be analysed for further confirmation.

Legal entity responsible for the study

Rajeswari Narayanappa

Funding

Department of Science and Technology, Govt of India

Funding

Department of Science and Technology, Govt of India

Disclosure

All authors have declared no conflicts of interest.

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Developmental therapeutics Poster lunch Poster Display session

137P - Prognostic factors of patients received immunocheckpoint inhibitors in oncology phase 1 trials (ID 1789)

Presentation Number
137P
Presentation Topic
Developmental therapeutics
Lecture Time
13:00 - 13:00
Speakers
  • T. Ebata
Authors
  • T. Ebata
  • T. Shimizu
  • S. Iizumi
  • T. Koyama
  • A. Shimomura
  • S. Iwasa
  • S. Kondo
  • S. Kitano
  • K. Yonemori
  • Y. Fujiwara
  • N. Yamamoto
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

To improve patient selection is crucial issue in phase 1 trial. Many prognostic factors and scoring systems such as the Royal Marsden Hospital score which includes serum albumin, LDH, and number of metastatic sites have been reported. However, it is unclear whether these factors could adapt to phase 1 trials of immunocheck point inhibitor because of the specific features and clinical course of immunotherapy. Therefore, we investigated the factors that have affected survival in oncology phase 1 trials of immunocheckpoint inhibitors.

Methods

We retrospectively evaluated 65 phase 1 trials at our institution conducted between June 2009 and November 2016 from our database. Patients who received immunocheck point inhibitors for advanced solid tumor were eligible. Some121 patients enrolled in 11 trials were eligible. Outcome and factors affecting survival were investigated.

Results

Eighty two events (67.8%) occurred. Median survival time (MST) of overall population from the day of administration of the investigational drugs was 12.8 months (95% confidence interval [CI]: 9.5-13.1). In univariate analysis, serum albumin ≺ 3.5g/dl, lactate dehydrogenase > normal upper limit, > 2 sites of metastasis, male, hemoglobin > 10.5 g/dl, neutrophil to lymphocyte ratio > 3 were significant poor prognostic factors. In multivariate analysis, serum albumin (hazard ratio [HR] 2.01 95% CI: 1.06-3.66), lactate dehydrogenase (HR 2.26 95%CI: 1.38-3.68), > 2 sites of metastasis (HR 3.86 95%CI: 2.31-6.44) and male (HR 2.22 95%CI: 1.30-3.86) were poor prognostic factors of overall survival.

Conclusions

In our study, the prognostic factors of overall survival in phase 1 trials of immunocheck point inhibitors were revealed similar features and were consistent with classical prognostic factors.

Legal entity responsible for the study

National Cancer Center Hospital

Legal entity responsible for the study

National Cancer Center Hospital

Funding

None

Disclosure

T. Shimizu: Reserch fund Bristol-Myers Squibb FivePrime PharmaMar honoreria ONO Pharmaceutical Co. Ltd. ONO Pharma Taiwan Co.Ltd. Chugai Pharmaceutical Co. Ltd. S. Kitano: Paid consultant for a company or supplier Ono. Daiichi-Sankyo. Astra Zeneca. Merek (MSD), Chugai, Eizai, Kyowa Kirin). Unpaid consultant for a company or supplier Boehringer Ingelheim,Ohtsuka, Merck Serono, Novaltis, Research support from a company or supplier Astellas, Gilead, Eizai, Regeneron Board member/committee appointments for a society Japanese Society of Medical Oncology,Japanese Association of Cancer Immunology, Japan Society for Biological Therapy, Japan Society of Urologic Oncology, Japanese Society of Renal Cancer, Y. Fujiwara: Grants/Research Support Recipient: AstraZeneca, BMS, Chugai, Daiichi-Sankyo, Eisai, Incyte, MerckSerono, MSD Speaker’s Bureau: BMS, ONO, Taiho, Boehringer Ingelheim, All other authors have declared no conflicts of interest. K. Yonemori: Lecture\'s fee Taiho, Eisai, Mochida, Novartis Grant Novartis. S. Iwasa: Research Grant: Bristol-Myers Squibb, Merck Serono, Chugai, Novartis, Lilly, Daiichi-Sankyo. Leuture\'s fee: Lilly. N. Yamamoto: Research grants: Quintiles, Astellas, Chugai, Eisai, Taiho, BMS, Pfizer, Novartis, Daiichi-Sankyo, Bayer, Boehringer Ingelheim, Kyowa-Hakko Kirin, Takeda, ONO. Advisory role: Eisai, Takeda, Onco Therapy Science. Speakers: BMS, Pfizer, AstraZeneca, Eli Lilly, ONO, Chugai

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Developmental therapeutics Poster lunch Poster Display session

138P - Clinical outcome and prognostic factors for patients treated in a phase I study at the National University Cancer Institute, Singapore (NCIS) (ID 1810)

Presentation Number
138P
Presentation Topic
Developmental therapeutics
Lecture Time
13:00 - 13:00
Speakers
  • C. Chee
Authors
  • C. Chee
  • R. Soo
  • B. Goh
  • W. Yong
  • S. Lee
  • D. Tan
  • A. Wong
  • W. Chng
  • V. Heong
  • B. Tai
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

Patient selection for phase I trials in oncology is challenging. A typical inclusion criterion for phase I studies is 'life expectancy >3 months', however overall survival (OS) of patients with advanced solid malignancies are difficult to predict. Other studies have demonstrated that despite the use of traditional eligibility criteria for enrollment into a Phase I (P1) study, about 1/3 of patients fail to meet all the necessary eligibility criteria at screening and ∼15-20% die within the first 90 days of P1 trial entry. The P1 Unit at the Royal Marsden Hospital (RMH), UK has found that a prognostic score is a helpful tool in the process of patient selection for P1 trial entry. We aim to develop a similar prognostic score predicting OS in our P1 patient population here at the NCIS.

Methods

Patients in P1 studies completed between Oct. 2013 – Jan. 2016 at NCIS and had EMR available were reviewed. Patient characteristics and survival data were analysed.

Results

120 pts from 10 completed P1 studies were included. Median age was 44.5 years (range: 23-79). Baseline variables were: age >60 (56%), male (53%), ECOG 0-1 (98%), comorbidities ≥2 (26%), no. of prior therapies ≥3 (65%), no. of metastatic sites ≥3 (40%). Univariate analysis revealed that albumin <35 g/L (HR: 3.23, 95% CI: 1.93 – 5.39, p < 0.001) and LDH >580 IU/L (HR: 1.95, 95% CI: 1.18 – 3.24, p = 0.009) were highly significant negative prognosticators for OS. The number of metastatic sites (>2 sites) was also at the threshold of significance (HR: 1.62, 95% CI: 0.99 – 2.64, p < 0.055). In the multivariable analysis of OS adjusting for tumour type, a high RMH prognostic score (2-3) vs. low score (0-1) was highly significantly for OS (HR: 3.67, 95% CI: 2.15 - 6.28), p < 0.001). OS according to the RMH prognostic risk score (high vs. low) for patients enrolled in P1 trials at the NCIS was 6 months and 16 months, respectively.

Conclusions

Risk scoring based on objective clinical parameters indicated that patients with a high score had a significantly shorter OS and this may assist in the selection of patient entry into P1 studies. A prospective study will be needed to test the validity of the prognostic score.

Legal entity responsible for the study

National University Cancer Institute, Singapore

Legal entity responsible for the study

National University Cancer Institute, Singapore

Funding

National University Cancer Institute, Singapore

Disclosure

All authors have declared no conflicts of interest.

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Developmental therapeutics Poster lunch Poster Display session

139P - Repurposing non-cancer drugs in oncology: Aspirin and metformin are only the tip of the iceberg (ID 1732)

Presentation Number
139P
Presentation Topic
Developmental therapeutics
Lecture Time
13:00 - 13:00
Speakers
  • B. Gyawali
Authors
  • B. Gyawali
  • P. Pantziarka
  • L. Meheus
  • G. Bouche
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

Drug repurposing can speed up access to new therapeutic options for cancer patients. With more than 2,000 drugs approved worldwide (DrugBank), and an average of 6 relevant targets per drug (Mestres, Nature Biotechnol, 2008; 26: 983), multiple opportunities for repurposing exist. Drug repurposing also represents an efficient way to adapt to new knowledge about cancer. For instance, tadalafil inhibits myeloid-derived suppressor cells in cancer patients at doses approved for erectile dysfunction. Many non-cancer drugs could be potentially repurposed against cancer. We attempted to quantify the number of non-cancer drugs that could potentially be repurposed in cancer treatment on the basis of supporting preclinical or clinical data.

Methods

A literature search (PubMed) was performed to identify non-cancer drugs which could be repurposed in oncology. Eligible drugs needed at least one peer-reviewed article showing an anticancer effect in vitro, in vivo or in humans.

Results

A total of 231 eligible non-cancer drugs were identified. 67 (29%) are on the WHO list of essential medicines and 157 (68%) are off-patent. 117 (51%) had human data in cancer patient(s). Four were listed in clinical guidelines, namely thalidomide, all-trans retinoic acid, zoledronic acid and non-steroidal anti-inflammatory drugs (NSAID). In the first 3 cases, pharmaceutical companies took the lead and re-branded or re-formulated the drugs. This was not the case for NSAIDs, listed in desmoid tumours guidelines and used off-label. Several drugs have shown a survival benefit in randomized trials such as cimetidine (colorectal cancer), progesterone (breast cancer) or itraconazole (lung cancer). Of note, several other drugs induced responses in rare tumours (e.g. clarithromycin, timolol, propranolol).

Conclusions

The number of repurposing opportunities is high. Since the majority of drugs identified are off-patent, joint non-commercial clinical development by academic, governmental and philanthropic organizations is likely the best way to bring new therapeutic options to patients at low cost. Such an effort would be truly innovative and may relieve healthcare systems currently under high financial stress.

Legal entity responsible for the study

Anticancer Fund

Clinical trial identification

Not apploicable

Legal entity responsible for the study

Anticancer Fund

Funding

Anticancer Fund

Disclosure

All authors have declared no conflicts of interest.

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Developmental therapeutics Poster lunch Poster Display session

140P - Effects of sinomenine, cepharanthine, and tetrandrine on 2D and 3D cultured triple negative breast cancer cells (ID 1525)

Presentation Number
140P
Presentation Topic
Developmental therapeutics
Lecture Time
13:00 - 13:00
Speakers
  • A. Kiyomi
Authors
  • A. Kiyomi
  • R. Miyakawa
  • N. Uematsu
  • H. Ono
  • Y. Nakajima
  • T. Hirano
  • M. Sugiura
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

P-glycoprotein (P-gp) is known to contribute to chemotherapy resistance. Tetrandrine (TET) has been reported to inhibit P-gp function. Sinomenine (SIN) may have a similar efficacy, while its effect on P-gp have little been clarified. Cepharanthine (CEP), a structural TET analog, has little been investigated for its anti-cancer efficacy. 3-Dimensionally (3D) cultured spheroids reflect in vivo environment closer than 2-dimensionally (2D) cultured cells. Then, we aimed to investigate the suppressive efficacy of these herbal ingredients on the growth of 2D and 3D cultured triple negative breast cancer cells.

Methods

MDA-MB-231 cells were cultured in a well of normal flat bottom plate or DSeA-3D Plate filled with TGP. After incubating in 5% CO2 for one night, cells or spheroids were treated by alone/combination of doxorubicin (DOX), docetaxel (DOC), SIN, CEP, or TET and then further cultured for 48 or 72hs. After incubating, the cell viability in each well was evaluated by WST-8 assay. Likewise, cells or spheroids were treated by DOC and/or a P-gp inhibitor verapamil (Vera) and evaluated the cell viability.

Results

DOX or DOC alone suppressed 2D cultured MDA-MB-231 cells dose-dependently, and significant effects were observed by > 5 × 10−7M DOX or > 2 × 10−8M DOC (p < 0.05). However, 3D spheroids showed resistance, and 2 × 10−4M of DOC showed no effect. Combination of DOC and Vera did not significantly alter the cell viability compared with DOC alone in both 2D and 3D. For 2D, 0.03 to 100μg/mL of SIN had no effect on the cell viability, while 300μg/mL of SIN inhibited significantly (p < 0.05). Otherwise, CEP and TET showed similar effect on 2D cells and decreased the cell viability dose-dependently. Significant inhibitory effects were observed when >30μg/mL of these compounds alone were used (p < 0.05).

Conclusions

3D cultured TNBC cells showed chemotherapy resistance compared with 2D cultured cells, and it may not be because of P-gp. TET, SIN and CEP suppress the 2D cultured TNBC cells, and thus further studies are encouraging for their combined use with anti-cancer drugs.

Legal entity responsible for the study

Tokyo University of Pharmacy & Life Sciences

Legal entity responsible for the study

Tokyo University of Pharmacy & Life Sciences

Funding

None

Disclosure

All authors have declared no conflicts of interest.

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Developmental therapeutics Poster lunch Poster Display session

141P - Erbitux conjugated zinc oxide nanoparticles to enhance antitumor efficiency via targeted drug delivery system for breast cancer therapy (ID 1700)

Presentation Number
141P
Presentation Topic
Developmental therapeutics
Lecture Time
13:00 - 13:00
Speakers
  • K. Vimala
Authors
  • K. Vimala
  • K. Soundarapandian
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

Owing to the presence of multidrug resistance in tumor cells, conventional chemotherapy remains clinically intractable. To enhance the therapeutic efficacy of chemotherapeutic agents, targeting strategies based on polyethylene glycol coated zinc oxide nanoparticles modified with targeting ligands have gained significant attention in cancer therapy

Methods

We used the green‐bio method to synthesize folic acid modified erbitux conjugated zinc oxide nanoparticles complex for its use as a cancer‐targeted drug delivery system to achieve enhanced cellular uptake and anticancer efficacy. To investigate the expression level of E2F3 protein RT‐PCR and western blotting analysis was carried out.

Results

In the present investigation, we synthesized folic acid (FA)-modified polyethylene glycol coated zinc oxide nanoparticles (PEG-ZnO NPs) loaded with erbitux (ErB) using a bio organic method, followed by FA adsorption on the surface of NPs. The FA-modified PEG-ZnO NPs were characterized in terms of particle morphology and size, encapsulation efficiency and drug release. Furthermore, the cytotoxicity and cellular uptake of the drug-loaded PEG-ZnO NPs were evaluated in breast cancer cells in vitro. We found that FA-modified ErB-PEG-ZnO NPs showed the highest cytotoxicity effect and cellular uptake efficiency under folic acid receptor mediation in breast cancer cells compared with unmodified PEG-ZnO NPs and free drug. The cellular uptake efficiency of FA-modified PEG-ZnO NPs appeared to be facilitated by the applied PEG-ZnO NPs field, but the difference did not reach statistical significance.

Conclusions

This study illustrates that this proposed formulation can be used as one new alternative treatment for patients bearing inaccessible tumors. Thus, functionalized-ZnO NPs could be used as a novel nanomaterial for selective chemotherapy.

Clinical trial indentification

622/PO/c/02/CPCSEA/2014.

Clinical trial identification

622/PO/c/02/CPCSEA/2014.

Legal entity responsible for the study

Periyar University, Department of Zoology, Division of Cancer Nanomedicine

Funding

None

Disclosure

All authors have declared no conflicts of interest.

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Gastrointestinal tumours, colorectal Poster lunch Poster Display session

146P - Overall survival in the FOXFIRE-SIRFLOX-FOXFIRE global prospective randomized studies of first-line SIRT in patients with mCRC (ID 1191)

Presentation Number
146P
Presentation Topic
Gastrointestinal tumours, colorectal
Lecture Time
13:00 - 13:00
Speakers
  • H. Wasan
Authors
  • H. Wasan
  • G. Van Hazel
  • V. Heinemann
  • N. Sharma
  • J. Taieb
  • J. Ricke
  • M. Peeters
  • M. Findlay
  • P. Virdee
  • S. Love
  • J. Moschandreas
  • P. Dutton
  • V. Gebski
  • A. Gray
  • R. Sharma
  • P. Gibbs
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

The FOXFIRE randomized studies [FOXFIRE, SIRFLOX and FOXFIRE-Global (FF-SF-FFG)] were designed to evaluate the efficacy and safety of selective internal radiation therapy (SIRT) using yttrium-90 resin microspheres plus first-line chemotherapy for unresectable metastatic colorectal cancer (mCRC). The design and eligibility criteria of the three studies were similar, which facilitated this prospective combined analysis of overall survival (OS).

Methods

Chemotherapy-naïve mCRC patients with liver metastases unsuitable for curative resection/ablation were randomized (1:1) to the Control arm with standard oxaliplatin-based chemotherapy (mFOLFOX6 or OxMdG) ± bevacizumab, or the Test arm to receive the same chemotherapy, plus a single SIRT treatment. Limited extra-hepatic metastases and primary tumor in situ were included. The primary endpoint OS was analysed on an intention-to-treat basis using individual participant data. Secondary endpoints included progression-free survival (PFS), liver PFS, response rate and adverse events (AEs).

Results

A total of 1103 patients (Control arm n = 549; Test arm n = 554) with a median age of 63 years were enrolled. Median follow-up was 43.3 months. There was no difference in median OS between the two treatment arms (pooled hazard ratio [HR] 1.04; 95% confidence interval [CI], 0.90-1.19; p = 0.609) or in median PFS (pooled HR 0.90; 95% CI, 0.79-1.02; p = 0.108). The objective response rate was higher in the SIRT arm than in the Control arm (72.2% and 63.0%, respectively, p = 0.001). The risk of progression in the liver as a first event was lower in patients in the SIRT arm (pooled HR 0.51; CI 0.43-0.62; p < 0.001). There was a higher likelihood of grade 3-5 AEs in the Test arm than in the Control arm (74.0% vs 66.5%, respectively, p = 0.009). The addition of SIRT appeared to have a significant OS benefit in patients with right-sided tumors.

Conclusions

This combined analysis showed no improvement when SIRT is added to first-line oxaliplatin-fluorouracil chemotherapy. However, the addition of SIRT achieved higher tumor response rates and improved liver-specific PFS. The addition of SIRT appeared to have a significant OS benefit in patients with right-sided tumors.

Clinical trial identification

FOXFIRE has ISRCTN Registry number ISRCTN83867919. SIRFLOX and FOXFIRE-Global are registered with ClinicalTrials.gov with registration numbers NCT00724503 and NCT01721954, respectively.

Legal entity responsible for the study

FOXFIRE, SIRFLOX and FOXFIRE-Global trial investigators.

Funding

Bobby Moore Fund of Cancer Research U.K., the University of Oxford and Sirtex Medical Ltd.

Disclosure

,H. Wasan: grants, personal fees, non-financial support and other uncompensated work from Sirtex Medical., G. van Hazel, V. Gebski: compensation for participation in Advisory Committees from Sirtex., V. Heinemann: honoraria from Amgen, Roche, Sanofi and Sirtex for consulting roles, participation in advisory boards, and his institution has received study grants from Amgen, Merck, Roche, Sanofi and Sirtex., N. Sharma: honoria from Sirtex Medical, J. Taieb: honoraria from Genentech, Merck Serono, Amgen, Celgene, Sanofi, Eli Lilly/ImClone Systems., J. Ricke: personal fees and grants from Sirtex Medical., M. Peeters: research funding and personal fees from Sirtex Medical., M. Findlay: grants from Sirtex Medical., P. Virdee, S.B. Love, J. Moschandreas: h grants from Cancer Research UK, grants from Sirtex Medical and non-financial support from Sirtex Medical., P. Dutton: grants from Cancer Research UK, grants from Sirtex Medical and non-financial support from Sirtex Medical, A. Gray: grants from Cancer Research UK, R. Sharma: research funding, honoraria, and consultancy fees from Sirtex Medical., P. Gibbs: honoraria from Sirtex Medical for participation in advisory boards and for giving presentations.

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Gastrointestinal tumours, colorectal Poster lunch Poster Display session

147P - S-1/oxaliplatin (SOX) plus bevacizumab (Bev) as first line followed by S-1/irinotecan (IRIS) plus cetuximab (Cmab) as second line therapy in metastatic colorectal cancer (mCRC) (SOBIC trial) (ID 1528)

Presentation Number
147P
Presentation Topic
Gastrointestinal tumours, colorectal
Lecture Time
13:00 - 13:00
Speakers
  • Y. Nakamoto
Authors
  • Y. Nakamoto
  • R. Mikami
  • M. Umeki
  • Y. Tokunaga
  • T. Okumoto
  • T. Kawamura
  • H. Fujiwara
  • S. Doi
  • M. Noda
  • N. Tomita
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

S-1 combination therapy (SOX, IRIS) is expected to be promising and safe for mCRC. The SOBIC trial is a phase II trial designed to validate the effectiveness of first and second line oral combination chemotherapy (CT) in mCRC. This is the first report which evaluated the efficacy of S-1 combination CT for mCRC.

Methods

mCRC patients candidate were received first line SOX + Bev (7.5mg/kg of Bev, 130mg/m2 of oxaliplatin on day 1 and 80-120mg/day of S-1 for 2 weeks followed by a 1-week rest) followed by second line IRIS + Cmab (weekly Cmab 250 mg/m2 initial dose 400 mg/m2, 100 mg/m2 of irinotecan on day 1, 15 and 80-120mg/day of S-1 for 2 weeks followed by a 2-week rest) in KRAS wild patients, IRIS + Bev (5mg/kg of Bev on day 1, 15, 100 mg/m2 of irinotecan on day 1, 15 and 80-120mg/day of S-1 for 2 weeks followed by a 2-week rest) or IRIS (125 mg/m2 of irinotecan on day 1, 15 and 80-120mg/day of S-1 for 2 weeks followed by a 2-week rest) in KRAS mutant patients. The primary endpoint was second progression-free survival (PFS). The secondary endpoint included overall survival (OS), response rate (RR) in first and second line CT, R0 resection rate (R0-Rate) and safety. We estimated that a target sample size of 48 patients.

Results

Among 52 patients were enrolled from May 2010 to March 2013 in HCCSG hospitals. 50 (male gender 60%, median age 65: 38 to 77) patients were included in the efficacy analysis. Second PFS was 24.2 months (95%CI: 17.7 to 35.2), OS was 35.2 months (95%CI: 27.8 to not reached). RR was 46.3% in first line CT, 20% in second line CT, respectively. In first line CT 10 (20%) patients underwent surgery, and R0 resection was achieved in all of the operable cases (R0-Rate was 20%). Surgery rate in second line CT was 12.5%. The main grade 3-4 adverse events were sensory neuropathy (18%), fatigue (10%), and anorexia (8%).

Conclusions

First line SOX+Bev, second line IRIS+Bev or IRIS+Cmab or IRIS was considered to be beneficial for mCRC patients.

Clinical trial identification

SOBIC trial

Legal entity responsible for the study

Yoshihiko Nakamoto

Funding

None

Disclosure

All authors have declared no conflicts of interest.

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Gastrointestinal tumours, colorectal Poster lunch Poster Display session

148P - Update analysis of phase Ib study of FOLFOXIRI plus ramucirumab as first-line therapy for patients with metastatic colorectal cancer (ID 1611)

Presentation Number
148P
Presentation Topic
Gastrointestinal tumours, colorectal
Lecture Time
13:00 - 13:00
Speakers
  • T. Yamada
Authors
  • T. Yamada
  • Y. Kito
  • H. Satake
  • H. Taniguchi
  • Y. Horie
  • T. Esaki
  • T. Denda
  • K. Mori
  • K. Yamazaki
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

Ramucirumab (Rmab), an anti-VEGFR-2 antibody, inhibits VEGF-A, -C, -D binding and endothelial cell proliferation, although bevacizumab binds to and blocks circulating VEGF-A. We had presented the result of dose finding phase Ib study of FOLFOXIRI plus Rmab for metastatic colorectal cancer (mCRC) patients (pts) in the 19th World Congress on Gastrointestinal Cancer. Here we reported the update analysis.

Methods

The eligibility criteria included pts with unresectable colorectal adenocarcinoma, 20-75 years, ECOG PS 0-1 (pts > 70 years were eligible if their ECOG PS was 0), wild-type or heterozygous UGT1A1 *28 or *6, no history of prior chemotherapy, and adequate organ function. Three dose levels were planned as follows: oxaliplatin and Rmab dose was fixed at 85 mg/m2 and 8 mg/kg, respectively. Level 1: 5-fluorouracil (5-FU) 3200 mg/m2, irinotecan (IRI) 165 mg/m2, Level 0 as starting dose: 5-FU 2400 mg/m2, IRI 150 mg/m2, and Level -1: 5-FU 2400 mg/m2, IRI 120 mg/m2. The dose-limiting toxicity (DLT) was evaluated in the first cycle.

Results

We enrolled a total of 10 pts (4 pts in the Level 0 and 6 pts in the Level 1). The pts characteristics were as follows: median age, 64 (range, 44-68); male/female, 6/4; ECOG PS 0/1, 8/2; RAS wild/mutant, 1/9; UGT1A1 *1*1/*1*28, 4/6. One patient was excluded for the DLT evaluation due to lack of safety evaluation on cycle 1 day 8. No DLT was observed in the 9 DLT-evaluable pts. Among 8 pts who had at least one tumor evaluation, early tumor shrinkage, response rate and disease control rate was 87.5%, 75% and 100%, respectively. In the first 3-cycle, major adverse events were Grade (G) 4 neutropenia (n = 2), G3 neutropenia (n = 1), G3 hypertension (n = 2), G2 thrombocytopenia (n = 4), G2 anorexia (n = 3), G2 hypertension (n = 3), G2 fatigue (n = 2) and G2 proteinurea (n = 2). G-CSF was administered in 2 pts in the first cycle.

Conclusions

FOLFOXIRI plus Rmab showed a promising antitumor activity with acceptable toxicity, although this study had a small sample size. A randomized phase II study of FOLFIRI plus Rmab versus FOLFOXIRI plus Rmab (Level 1) for chemotherapy-naïve mCRC pts (WJOG9216G trial; UMIN000026527) is on-going.

Clinical trial identification

UMIN000023277.

Legal entity responsible for the study

Shizuoka Cancer Center

Funding

Shizuoka Cancer Center

Disclosure

All authors have declared no conflicts of interest.

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Gastrointestinal tumours, colorectal Poster lunch Poster Display session

149P - Efficacy and safety of CapeIRI plus bevacizumab therapy as a second-line treatment for patients with metastatic colorectal cancer (ID 1713)

Presentation Number
149P
Presentation Topic
Gastrointestinal t