- Giuseppe Curigliano
- Binghe Xu
1O - Differences in Prognosis and Efficacy of Chemotherapy by p53 Expression in Triple Negative Breast Cancer
- Soo Youn Bae
- Soo Youn Bae
- Seung Pil Jung
- Korean Breast Cancer Society Korean Breast Cancer Society
- Seok Jin Nam
- Yongsik Jung
- Byung Woo Park
- Woosung Lim
- Sung Hoo Jung
- Hong Kyu Kim
- Ji-Young You
- Sae Byul Lee
Abstract
Background
TP53 mutation is the most common mutation in breast cancer, and it is considered a target marker of triple negative breast cancer (TNBC). The purpose of this study was to evaluate the prognosis of TNBC using only clinical information. The p53 status detected immunohistochemically was evaluated as a prognostic and predictive factor.
Methods
Among KBCSR-registered patients, triple-negative breast cancer patients diagnosed between 2000 and 2015 were included. This included patients who were aged 20 years or older and had between stage I and stage III TNBC. A total of 11,393 patients were included in this study, including 6,331 ‘p53-positive TNBC’ and 5,062 ‘p53-negative TNBC’ cases. The median follow-up period was 60 months (1-188 months).
Results
In univariate analysis, there was no difference in prognosis between p53+ TNBC and p53- TNBC for patients receiving chemotherapy. But, p53+ TNBC had a worse prognosis than p53- TNBC in patients not receiving chemotherapy (P = 0.003). In multivariate analysis adjusted for age and cancer stage, the risk of p53+ TNBC was 1.84 times higher than that of p53- TNBC in the non-chemotherapy group. There was no difference between p53+ TNBC and p53- TNBC in patients receiving chemotherapy. In p53+ TNBC, the risk was 0.6-fold lower when chemotherapy was administered than when chemotherapy was not administered. In p53- TNBC, there was no risk reduction effect by chemotherapy.
Conclusions
The prognosis of p53- TNBC is better than that of p53+ TNBC, but it shows no benefit of chemotherapy. p53+ TNBC has a poor prognosis but benefits from chemotherapy. In conclusion, p53+ TNBC appears to be more sensitive to chemotherapy than p53- TNBC.
Legal entity responsible for the study
Soo Youn Bae.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
23O - Implications of Plasma Deoxyribonucleic Acid Topoisomerase 2 Beta Level in Breast Cancer Patients receiving Doxorubicin-Based Chemotherapy
- Thurein Win
- Thurein Win
- Tun Tun Naing
- Tun Tun Win
- Kyaw Kyaw Aung
- Yin Yin Htun
Abstract
Background
Doxorubicin is the most preferred cytotoxic agent to be incorporated in chemotherapy regimens for breast cancer. However, its use is limited by cardiotoxicity which cannot be predicted using currently available methods. Plasma deoxyribonucleic acid topoisomerase 2β level (DNA Top 2β) is potential to be an early predictor of anthracycline-induced cardiotoxicity. Aim of the study is to assess the implications of plasma DNA Top 2β level in breast cancer patients receiving a doxorubicin-based chemotherapy regimen.
Methods
All newly diagnosed breast cancer patients, who were going to receive a new course of doxorubicin-based chemotherapy was recruited over 12 months and assessed comprehensively in No. (2) Military Hospital (500-Bedded). After informed consent, eligible patients received six cycles of doxorubicin-based chemotherapy with serial serum troponin I and LVEF assessments on the day after each cycle. LVEF <50% or ≥ 10% decline from baseline was regarded as indication to stop doxorubicin-based chemotherapy.
Results
Among fifty-one patients, mean age was 48.78 years. While mean plasma Top 2β level was 0.43 ng/μg, about a quarter of patients (25.5%) expressed ≥0.5 ng/μg. There was no significant association between plasma Top 2β level and each baseline clinical characteristics (age, hypertension, diabetes, dyslipidaemia and clinical staging). Throughout chemotherapy, no positive result of serum troponin I was observed while 16 patients had significant LVEF decline. There was significant association between higher Top 2β level (≥ 0.5 ng/μg) and LVEF decline (P = 0.001). Mean plasma Top 2β level was higher in patients with LVEF decline [0.74 ng/μg (S.D ±0.70)] than those without decline [0.29 ng/μg (S.D ±0.30)] (P < 0.05). Log-rank test showed that patients expressing higher Top 2β level (≥ 0.5 ng/μg) had higher propability of LVEF decline over time (p = 0.001).
Conclusions
LVEF decline is associated with higher plasma DNA Top 2β level in breast cancer patients receiving doxorubicin-based chemotherapy. Given no association with other cardiovascular risk factors, plasma DNA Top 2β is a potential independent biomarker to predict cardiac risk of anthracycline in cancer patients.
Legal entity responsible for the study
Defence Services Medical Academy.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
40O - Biomarker analyses of Asian women with hormone receptor-positive (HR+), HER2-negative (HER2–) advanced breast cancer (ABC) receiving ribociclib (RIB) + endocrine therapy (ET)
- Yoon Sim Yap
- Yoon Sim Yap
- Norikazu Masuda
- Yoshinori Ito
- Takashi Ishikawa
- Seung Jin Kim
- Tomoyuki Aruga
- Tatsuya Toyama
- Toshiaki Saeki
- Takashi Yamanaka
- Mitsue Saito
- Junichiro Watanabe
- Masato Takahashi
- Seigo Nakamura
- Kenichi Inoue
- Jose Suarez-Vizcarra
- Wei He
- Nadia Solovieff
- Faye Su
- Joanne Chiu
Abstract
Background
The ongoing Phase Ib MONALEESASIA (NCT02333370) study is a dose-escalation (RIB + letrozole [LET]) and dose-expansion (RIB + LET, fulvestrant [FUL], or tamoxifen [TAM]) study in Asian patients (pts) with HR+, HER2– ABC; here we present biomarker analyses.
Methods
In the dose escalation, postmenopausal pts with HR+, HER2– ABC (no prior therapy for ABC) received RIB (300, 400, or 600 mg/day [d]; 3 weeks on/1 week off) + LET (2.5 mg/d). In the dose expansion, pre- and postmenopausal pts (≤1 line of any prior therapy for ABC) received RIB (recommended Phase II dose) + LET (2.5 mg/d), FUL (500 mg, d1 and 15 of Cycle [C] 1, then every 28 d), or TAM (20 mg/d) + goserelin (3.6 mg every 28 d; premenopausal pts only). Baseline (BL) and on-treatment (OT; collected at d15 of C1) samples were assessed for dynamic changes in messenger RNA expression (NanoString 230-gene nCounter® GX Human Cancer Reference panel). Differences in gene expression between pre- and postmenopausal pts were assessed using a Mann-Whitney-Wilcoxon test.
Results
As of Mar 2, 2018, BL tumor mRNA expression was evaluated in 68 of 88 pts. Dynamic gene expression changes were assessed in 5 pts with paired BL/OT samples, with an observed decrease in mRNA expression of E2F-responsive (e.g. E2F1, MYC, and TYMS) and cell cycle-related genes (e.g. CDK genes). Super responders (n = 5; no progression ≥24 months post-randomization) and poor responders (n = 6; progressed ≤8 weeks post-randomization) showed differential expression of cell cycle-, proliferation-, and breast cancer-related genes. Genes with different expression levels between pre- (n = 9) and postmenopausal Japanese pts (n = 31) were identified. BL circulating tumor DNA analysis by next-generating sequencing (n = 82) will be presented.
Conclusions
In Asian pts with HR+, HER2– ABC, suppression of pharmacodynamic biomarker gene expression, including E2F-responsive genes, indicated that RIB + ET inhibited the intended targets. Differences in BL gene expression patterns were observed between pts with sustained responses vs those who progressed ≤2 treatment cycles. Due to small pt numbers, further investigation is needed.
Editorial acknowledgement
Editorial assistance was provided by Claire Wilson, PhD, of ArticulateScience Ltd.
Clinical trial identification
NCT02333370.
Legal entity responsible for the study
Novartis Pharmaceuticals Corporation.
Funding
Novartis Pharmaceuticals Corporation.
Disclosure
Y.S. Yap: Personal fees and non-financial support: Novartis, Pfizer, AstraZeneca, Eisai; Personal fees: Eli-Lilly, Roche. N. Masuda: Personal fees: Chugai, AstraZeneca, Pfizer, Kyowa-Kirin, Eisai, Takeda, Eli-Lilly. Y. Ito: Grants: Daiichi Sankyo, Chugai, Novartis, Parexel, EPS, MSD, AstraZeneca, Lilly, Kyowa Hakko Kirin, Covance, Taiho, A2 Healthcare. S.J. Kim: Personal fees: Novartis. T. Toyama: Grants: Novartis Pharma, Eisai, Chugai Pharmaceutical, Nippon Kayaku, Pfizer Japan Inc., Kyowa Hakko Kirin, Taiho Pharma, Daiichi Sankyo, Takeda Pharmaceutical. T. Saeki: AstraZeneca, Eisai, Ono, Kyowa Hakko Kirin, Sanofi, TaishoToyama, Taiho, Takeda, Chugai, Bayer Yakuhin, Fuji, Daiichi Sankyo, Nihon Medi-Physics, Nippon Kayaku, Novartis, Hamamatsu Photonics, Medicon, MSD, Global Software Inc, KyowaHakkoKirin, Taiho. T. Yamanaka: Personal fees: Novartis, Chugai, Pfizer, Taiho, outside the submitted work. J. Watanabe: Personal fees: Novartis Pharma, outside the submitted work. S. Nakamura: AstraZeneca, Chugai Pharmaceutical, Daiichi Sankyou, Eisai, Ltd., Kkyowa Hakko Kirin, Nipponn Kayaku, Novartis Pharma K.K., Pfizer Japan Inc., Taiho Pharmaceutical, Takeda Pharmaceutical. K. Inoue: Institutional grants: Novartis, Pfizer, Chugai, Daiichi Sankyo, Parexel / Puma Biotechnology, MSD, Bayer, Lilly, Esai. J. Suarez-Vizcarra, W. He: Employee: Novartis. N. Solovieff, F. Su: Employee, stock holder: Novartis. All other authors have declared no conflicts of interest.
41O - Decreased mortality strongly correlated with the upregulation of BCR in breast cancer metastasis to bone
- Si Nguyen T. Mai
- Si Nguyen T. Mai
- Huyen N. Vu
- Xuan The Hoang
- Van Thai Than
- Trung V. Nguyen
- Minh Thong Le
- Phuc-Loi Luu
- Hoa Q. Tran
- Minh Nam Nguyen
Abstract
Background
Metastatic breast cancer frequently spreads to bone due to the large reservoir of available tissue contained within the human skeleton and the environmental conditions which surround it. However, it remains unclear why only a subset of cancer patients develops bone metastasis. As those with bone metastasis have increased mortality rates among cancer patients, there is a need to investigate the molecular factors that drive cancer metastasis to bone tissue and the biomarkers that are most predictive of skeletal metastasis. Data were collected and analyzed to determine the correlation between metastatic bone cancer and Breakpoint Cluster region (BCR), one such molecular factor hypothesized to assist in bone metastasis.
Methods
Clinical information and gene expression data were retrieved from GEO and Array express, including GSE2034 (n = 284), GSE2603 (n = 82), and E-MTAB-365 (n = 115). Raw data were processed using a robust, multiarray averaging method for normalization. Kaplan-Meier curves, Chi-square, and log-rank tests were performed using R to evaluate the prognostic value of BCR. In all statistical analyses, a p-value of less than 0.05 was considered significant.
Results
It was found that expression of BCR was significantly low in breast cancer tissues of patients with bone metastasis (p = 5.43e-11). Breast cancer patients with high expression levels of BCR had better bone metastasis-free survival outcomes (p = 5.43e-13). In addition, BCR was identified as an independent predictor of bone metastasis in univariate [HR = 3.43, 95% CI = 2.40–4.90; p = 5.43e-13] and multivariate analysis [HR = 3.19, 95% CI = 2.21–4.61; p = 6.25e-10]. Intriguingly, BCR also helps to obtain greater insights into the heterogeneity of triple negative breast cancer.
Conclusions
BCR is a powerful predictor in gaining greater insights into the heterogeneous landscape of bone metastatic in breast cancer. Moreover, by integrating into the molecular subtypes, BCR can further sub-classify patients into two risk groups, thereby enabling more informed therapeutic decisions and improved prognostics for breast cancer. Together, these findings point to the general utility of this biomarker in the age of precision medicine.
Legal entity responsible for the study
Ton Duc Thang University.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.