Sessions are scheduled in local time (CEST)
Browsing Over 485 Presentations
184P - PGS000508 as a Prediction for Breast Cancer Risk in Taiwanese Populations (ID 396)
- Yi-Hsuan Lin (Taichung City, Taiwan)
- Yi-Hsuan Lin (Taichung City, Taiwan)
- Chih-Chiang Hung (Taichung City, Taiwan)
- Tzu-Hung Hsiao (Taichung City, Taiwan)
- Chih-Yean Lum (Taichung City, Taiwan)
Abstract
Background
Breast cancer has been the most common cancer diagnosed among women in Taiwan since 2003. Genetic variants account for high risks of developing breast cancer was less studied in Asian population. Many researches had discovered variant polygenic risk score (PRS) to evaluate the risk of developing breast cancer. This study aims to determine a predictive breast cancer PRS for Taiwanese populations and assess the heterogeneity in the relationships with breast cancer risk by biomarker testing, age at diagnosis, clinical and pathological stages.
Methods
The development dataset comprised 28,443 control subjects and 1,501 case subjects from Taiwan Precision Medicine Initiative (TPMI) array and breast cancer registry lists in Taichung Veterans General Hospital (TCVGH). Samples were analyzed by using breast cancer associated PGS Catalog, and significant PGSs were selected by stepwise logistic regression. The best performing PGS was yielded and 1,501 breast cancer patients were evaluated for further heterogeneity of breast cancer risk analysis.
Results
Logistic regression results showed PGS000508 were significantly associated with breast cancer risk after multiple testing (odds ratio, 3.57; P=1.0850 E-53). Dose-response association was observed. Women in the highest quartile had a significantly increased risk compared to women in the lower quartile( odds ratio, 1.95; 95% confidence interval 1.75-2.17; P=3.54 E-34). Over 1,501 breast cancer diagnosed women stratified by PRS distribution, the highest quartile women had more advanced pathological stage (p=0.03); younger age while first diagnosis (p=0.01) and positive hormone status (p=0.03) compared to women in the lower quartile.
Conclusions
Our study identified PGS000508 as a risk predictor of breast cancer among Taiwanese women as well as advanced pathological stage, positive hormone status and younger age at first diagnosis.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
12P - HER2DX in HER2-positive (HER2+) Inflammatory Breast Cancer (IBC): a correlative analysis from a phase II clinical trial (ID 232)
- Adrienne G. Waks (Boston, MA, United States of America)
- Filipa Lynce (Boston, MA, United States of America)
- Fara Brasó-Maristany (Barcelona, Spain)
- Adrienne G. Waks (Boston, MA, United States of America)
- Patricia Villagrasa Gonzalez (Barcelona, Spain)
- Guillermo Villacampa (Barcelona, Spain)
- Esther Sanfeliu Torres (Barcelona, Spain)
- Patricia Galván (Barcelona, Spain)
- Laia Pare Brunet (Barcelona, Spain)
- Leilani Anderson (Boston, United States of America)
- Charles M. Perou (Chapel Hill, NC, United States of America)
- Joel Parker (Chapel Hill, United States of America)
- Ana Vivancos (Barcelona, Spain)
- Molly Dilullo (Boston, MA, United States of America)
- Sonia Pernas Simon (L'Hospitalet de Llobregat, Spain)
- Eric P. Winer (New Haven, United States of America)
- Beth Overmoyer (Boston, United States of America)
- Elizabeth A. Mittendorf (Boston, United States of America)
- Aleix Prat (Barcelona, Spain)
- Sara M. Tolaney (Boston, MA, United States of America)
Abstract
Background
HER2DX is a 27-gene assay for early-stage HER2+ breast cancer based on clinical data and the expression of 4 signatures (immune, proliferation, luminal, and HER2). Here we evaluated the utility of HER2DX in HER2+ IBC for the first time.
Methods
Standardized HER2DX was evaluated centrally on baseline pre-treatment tumors from a prospective phase II clinical trial (NCT01796197), in which patients with HER2+ IBC were treated with neoadjuvant paclitaxel, trastuzumab and pertuzumab (THP) x 16 weeks. The primary aim of this correlative analysis was to evaluate the pCR rates (ypT0/isN0) according to HER2DX pCR-score pre-defined cutoffs (i.e., low, medium, and high). Secondary objectives were to compare the HER2DX scores and signatures in IBC vs. stage II-III HER2+ non-IBC treated with neoadjuvant THP x 12 weeks on trial (NCT03716180). Descriptive statistics were used. Means between the two groups were compared using a Student´s t-test.
Results
HER2DX was evaluated in 23 patients with HER2+ IBC (
Study IBC non-IBC 23 80 19/21 (90.5%) 68/78 (87.2%) 23 (100%) 0 21 (91.3%) 28 (35%) 12 (52.2%) 56 (70%) 10 (43.5%) 48 (60%) 22 (95.7%; 78.1-99.9%) 39 (48.8%; 37.4-60.2%) 8 (34.8%; 16.4-57.3%) 31(38.8%; 28.1-50.3%) 11 (47.8%; 26.8-69.4%) 22 (27.5%;18.1-38.6%) 4 (17.4%; 4.9-38.8%) 27 (33.8%; 23.6-45.2%)
Conclusions
HER2DX pCR-high designation may be less frequent in HER2+ IBC compared to HER2+ non-IBC. Lower mRNA expression of HER2 amplicon genes, and higher tumor burden at diagnosis, might explain the differences observed in the distribution of HER2DX scores and signatures between HER2+ IBC and non-IBC.
Clinical trial identification
NCT01796197.
Legal entity responsible for the study
The authors.
Funding
Reveal Genomics.
Disclosure
F. Lynce: Financial Interests, Personal and Institutional, Advisory Board, PI of clinical trial: AstraZeneca; Financial Interests, Personal, Advisory Board: Pfizer, Merck, Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Incyte, Eisai, CytomX. F. Brasó-Maristany: Financial Interests, Personal, Invited Speaker: Reveal Genomics. A.G. Waks: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Institutional, Invited Speaker: Genentech, Macrogenics, Merck. P. Villagrasa Gonzalez: Financial Interests, Personal, Full or part-time Employment: Reveal Genomics; Financial Interests, Personal, Other, Co-Founder: Reveal Genomics. G. Villacampa: Financial Interests, Personal, Invited Speaker, Invited speaker in a course: MSD; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Invited Speaker, Invited speaker in an internal training: Pierre Fabrer, GSK; Financial Interests, Personal, Invited Speaker, Internal discussion about the interpretation of some published results: Pfizer; Financial Interests, Personal, Other, Collaborations with specific projects: Reveal Genomics. L. Pare Brunet: Financial Interests, Institutional, Full or part-time Employment: Reveal Genomics S.L.; Financial Interests, Institutional, Other, Patent pending: In vitro method for the prognosis of patients suffering from HER2-positive breast cancer - 905333: Reveal Genomics S.L. C.M. Perou: Financial Interests, Personal, Invited Speaker: GeneCentric Therapeutics; Financial Interests, Personal, Stocks/Shares: GeneCentric Therapeutics, Bioclassifier LLC, Reveal Genomics; Financial Interests, Personal, Royalties, from PAM50 licensing: Bioclassifier LLC; Financial Interests, Personal, Royalties: GeneCentric Therapeutics; Non-Financial Interests, Advisory Role: GeneCentric Therapeutics, Bioclassifier LLC, Reveal Genomics. J. Parker: Financial Interests, Personal, Other, Advisory: Reveal Genomics, Bristol Myers Squibb; Financial Interests, Personal, Full or part-time Employment: LifeEdit Therapeutics; Financial Interests, Personal, Ownership Interest: Reveal Genomics, GeneCentric; Financial Interests, Personal, Royalties: Veracyte. A. Vivancos: Financial Interests, Personal, Advisory Board: Roche, Bristol Meyers Squibb, Guardant Health, Bayer, Incyte; Financial Interests, Personal, Stocks/Shares: Reveal Genomics; Financial Interests, Institutional, Research Grant, Preclinical Research Grant: Bristol Meyers Squibb, Roche, Incyte. S. Pernas Simon: Financial Interests, Personal, Advisory Board: Seagen, AstraZeneca- Daiichi Sankyo, Pierre-Fabre, Pfizer; Financial Interests, Personal, Invited Speaker: Lilly, Novartis, Eisai, Roche; Financial Interests, Institutional, Invited Speaker: AstraZeneca, Novartis, Daiichi-Sankyo; Non-Financial Interests, Invited Speaker: SOLTI. E.P. Winer: Financial Interests, Institutional, Research Grant: Genentech/Roche; Financial Interests, Personal, Advisory Board: Athenex, Carrick Therapeutics, G1 Therapeutics, Genentech/Roche, Genomic Health, Gilead, GlaxoSmithKline, Jounce, Lilly, St Lucia, Syros, Zymeworks; Non-Financial Interests, Personal, Advisory Board, non-paid: Leap Therapeutics; Other, Personal, Leadership Role, President: ASCO. E.A. Mittendorf: Financial Interests, Personal, Advisory Board: Merck, BioNTech; Financial Interests, Institutional, Research Grant, I have a grant from SU2C funded by Roche/Genentech that supports the conduct of a clinical trial: Roche/Genentech; Financial Interests, Institutional, Invited Speaker, Gillead provides clinical trial support to my institution for a study that I am the PI on: Gillead; Financial Interests, Personal, Invited Speaker: Roche/Genentech, BMS; Non-Financial Interests, Invited Speaker: American Society of Clinical Oncology; Non-Financial Interests, Advisory Role, I serve in an advisory role as a Komen Scholar: Komen for the Cure. A. Prat: Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker, Lecture fees: Novartis, Daiichi Sankyo; Financial Interests, Personal, Advisory Board, Advisory role/consultancy: Novartis, Pfizer, Oncolytics Biotech, Guardant Health, Peptomyc; Financial Interests, Institutional, Invited Speaker, Clinical trials: Daiichi Sankyo; Financial Interests, Institutional, Other, Contracted research: Boehringer, Medica Scientia inno. Research; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Invited Speaker, Leadership role: Reveal Genomics, SL.; Financial Interests, Personal, Stocks/Shares: Reveal Genomics, Oncolytics Biotech; Financial Interests, Personal, Royalties: Reveal Genomics; Financial Interests, Institutional, Invited Speaker: Roche, AstraZeneca, Novartis; Financial Interests, Personal and Institutional, Invited Speaker: Daiichi Sankyo; Non-Financial Interests, Institutional, Other, Leadership roles: Patronage committee: SOLTI Foundation, Actitud Frente al Cáncer Foundation; Non-Financial Interests, Personal, Other, Asociación Española de Investigación sobre el Cáncer: ASEICA. S.M. Tolaney: Financial Interests, Personal, Advisory Board, Ad Board Participant/Consultant: AstraZeneca, Eli Lilly; Financial Interests, Personal, Advisory Board, Ad board participant/Consultant: Pfizer; Financial Interests, Personal, Advisory Board, Ad board participant/consultant: Novartis, Gilead, Genentech/Roche, Eisai, Sanofi, Seagen, Daiichi Sankyo, 4D Pharma, ARC Therapeutics; Financial Interests, Personal, Advisory Board, Ad Board participant/consultant: Merck; Financial Interests, Personal, Advisory Board, Ad board participant: Bristol Myers Squibb, Mersana Therapeutics, Ellipses Pharma; Financial Interests, Personal, Other, Steering Committee Member/Consultant: CytomX; Financial Interests, Personal, Other, Consultant: Blueprint Medicines; Financial Interests, Personal, Advisory Board, Advisory Board Participation: Zymeworks; Financial Interests, Personal, Advisory Board, Advisory Board participation: Zentalis, OncXerna, Myovant, Bayer, Zetagen, Infinity Therapeutics, Umoja Biopharma; Financial Interests, Personal, Advisory Board, Advisory board participation: Reveal Genomics; Financial Interests, Personal, Advisory Board, Advisory Board participation/consulting: Menarini/Stemline; Financial Interests, Personal, Other, Consulting: Aadi BioPharma; Financial Interests, Institutional, Funding: AstraZeneca, Eli Lilly, Pfizer, Sanofi, Seagen, Odonate, Cyclacel, Exelixis, Gilead, Bristol Myers Squibb, Eisai, Merck, Novartis, Nektar, Genentech/Roche; Financial Interests, Personal and Institutional, Invited Speaker: CytomX. All other authors have declared no conflicts of interest.
Recent progresses on the treatment of luminal metastatic breast cancer with CDK 4/6 inhibitors (ID 61)
- Gustavo Werutsky (Porto Alegre, Brazil)
- Gustavo Werutsky (Porto Alegre, Brazil)
220P - Oral Selective Estrogen Receptor Degraders for metastatic hormone receptor-positive, HER2 negative breast cancer according to ESR1 mutation: a systematic review and meta-analysis of randomized control trials. (ID 424)
- Roberto Gabriel Santiago Novello (Sao Paulo, Brazil)
- Roberto Gabriel Santiago Novello (Sao Paulo, Brazil)
- Matheus Lobo (Sao Paulo, Brazil)
- Maysa Silveira Vilbert (Toronto, Canada)
- Solange M. Sanches (Sao Paulo, SP, Brazil)
- Marcelle G. Cesca (Sao Paulo, Brazil)
Abstract
Background
Oral selective estrogen receptor degraders (SERDs) are a promising treatment after disease progression on first-line endocrine therapy (ET) for hormone receptor-positive (HR+), HER2 negative advanced breast cancer (aBC) patients. This systematic review and meta-analysis of randomized clinical trials (RCTs) aimed to assess the efficacy of oral SERDS versus standard of care (SOC) ET according to ESR1 mutation (ESR1mut).
Methods
We searched PubMed, Embase, Cochrane, Web of Science, and congresses websites (ASCO and ESMO) for RCTs including HR+/HER2 negative aBC patients who were randomized to oral SERDs versus SOC ET and had received at least one prior line of ET. Outcomes of interest were progression-free survival (PFS) according to ESR1mut and objective response (ORR). Heterogeneity was evaluated with I2 statistics, and random-effect models were fitted.
Results
Of 519 studies screened, four RCTs were included, comprising 1290 patients, of whom; 41% harbored ESR1mut, 92.5% were postmenopausal, and 66% had visceral metastasis. Prior treatment for aBC included iCDK4/6 (73.3%), chemotherapy (21.6%), and; 25.2% of patients received ≥ two prior ET. In a pooled analysis, oral SERDs significantly improved PFS compared to SOC ET (HR 0.76 [95% CI 0.63-0.93 p=0.007]). ESR1mut patients treated with SERDs achieved a significant prolonged PFS than SOC ET (HR 0.59 [95% CI 0.45-0.77 p<0.001]), which was not seen in the wild-type ESR1 group (HR 0.84 [95%CI 0.67-1.04 p=0.11]). ORR was 11% in patients treated with SERDs and 7.4% in SOC ET (p=0,06). N: number; SERD: Selective Estrogen Receptor Degrader; SOC: standard of care; ET: endocrine therapy; mut: mutant; NA: not available.
Trial Phase N Follow-up Median, months Oral SERD (N) SOC ET (N) ESR1mut Bidard, 2022 III 477 15.1 Elacestrant (239) Fulvestrant, AI (238) 228 Oliveira, 2022 II 147 16.6 Arm 1: camizestrant 75mg (74) Fulvestrant (73) 88 146 Arm 2: camizestrant 150mg (73) 88 Tonaley, 2022 II 290 NA Amcenestrant (143) Fulvestrant, AI, tamoxifen (147) 120 Jimenez, 2022 II 303 7.89 Giredestrant (151) Fulvestrant, AI (152) 90
Conclusions
Oral SERDs improved PFS compared to SOC ET for ESR1mut HR+/HER2 negative metastatic breast cancer, but not for unselected patients.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
M. Lobo: Financial Interests, Personal, Invited Speaker: MSD, Novartis. S.M. Sanches: Financial Interests, Personal, Invited Speaker: MSD, AstraZeneca, Daiichi Sankyo. M.G. Cesca: Financial Interests, Personal, Invited Speaker: Novartis, Zodiac, Daiichi; Financial Interests, Personal, Principal Investigator: AstraZeneca, Sanofi, Seagen. All other authors have declared no conflicts of interest.
39P - A validation study of a self-testing capillary kit, the rhelise™ kit for therapeutic dose monitoring (TDM) of tamoxifen, Z-endoxifen, and 4-hydroxytamoxifen in breast cancer patients (ID 259)
- Elham Hedayati (Solna, Sweden)
- Elham Hedayati (Solna, Sweden)
- Ivan Shabo (Solna, Sweden)
- Per Rydberg (Stockholm, Sweden)
- Stefan Rehnmark (Sodertalje, Sweden)
- Håkan Randahl (Sodertalje, Sweden)
- Annelie Lindqvist (Sodertalje, Sweden)
- Per F. Hall (Stockholm, So, Sweden)
- Jenny Bergqvist (Stockholm, Sweden)
- Yvonne Wengstrom (Huddinge, Sweden)
Abstract
Background
Tamoxifen is an effective drug reducing the risk of dying from breast cancer. This study aims to validate and study the feasibility of serial assessments, including therapeutic drug monitoring of tamoxifen (TAM), 4-hydroxytamoxifen (4HT) and Z-endoxifen (Z-END) by capillary blood sampling.
Methods
A prospective, single-centre study including women with stage 0-3 breast cancer receiving adjuvant tamoxifen 20 mg/day for a minimum of 2 months. Study design: Blood samples for repeated measurement of TAM, 4HT and Z-END were drawn capillary in total at 4-time points, at inclusion (baseline), and after 1, 2, and 3 weeks for each participant; and venously in total at two time-points, at inclusion (baseline), and after 3 weeks for each participant. At baseline, the capillary blood test concentrations of TAM, 4HT and Z-END were taken first by the research nurse and second by the patient. At each time, participants will be asked to leave 1 vial of capillary blood using the rhelise™ kit and 2 samples of conventional venous blood for blood and plasma. Primary Objective To validate the rhelise™ kit for monitoring TAM, 4HT and Z-END among patients who have ongoing adjuvant tamoxifen by testing for equivalence between concentrations found in the capillary sample and the venous blood sample (gold standard). Primary endpoint Blood concentrations and correlations of TAM, 4HT and Z-END at baseline and 3 weeks by capillary and venous blood sampling (whole blood/plasma). Secondary objectives To validate user acceptability and feasibility of self-testing the capillary kit by comparing the capillary blood test concentrations of TAM, 4HT and Z-END taken by the patient to the capillary sample taken by the research nurse. Secondary endpoints Capillary blood test concentrations of TAM, 4HT and Z-END were taken by the patient and the research nurse at baseline.
Results
A capillary sampling kit was used for 40 participants. Mean TAM, 4HT and Z-END concentrations did not differ significantly in the 3 types of samples. Mean capillary TAM, 4HT and Z-END concentrations did not differ significantly between nurse and patient.
Conclusions
TDM of TAM using capillary blood sampling is feasible.
Clinical trial identification
NCT05133674.
Legal entity responsible for the study
Elham Hedayati, Karolinska University Hospital.
Funding
Vinnova & Karolinska University Hospital, Karolinska Institutet.
Disclosure
S. Rehnmark, H. Randahl: Financial Interests, Personal and Institutional, Ownership Interest: Redhotdiagnostics AB. A. Lindqvist: Financial Interests, Personal and Institutional, Full or part-time Employment: Redhotdiagnostics AB. All other authors have declared no conflicts of interest.
Q&A and discussion (ID 89)
- To be Announced (Barcelona, Spain)
- To be Announced (Barcelona, Spain)
254P - The invasive lobular cancer of the breast (ILC): a collection of clinical and pathological data in patients with (non-)metastatic breast cancer (BC) (ID 457)
- Toni Ljubicic (Berlin, Germany)
- Toni Ljubicic (Berlin, Germany)
- Therese Pross (Berlin, Germany)
- Adam D. Dordevic (Berlin, Germany)
- Robert Röhle (Berlin, Germany)
- Pimrapat Gebert (Berlin, Germany)
- Paul Jank (Marburg, Germany)
- Maria M. Karsten (Berlin, Germany)
Abstract
Background
ILC is the second most common BC type after the invasive carcinoma of no special type (NST). It mostly presents as estrogen receptor (ER) and progesterone receptor (PR) positive, human epidermal growth receptor 2 (HER2) negative and with a low marker of proliferation (Ki67) which results in a luminal A subtype and E-cadherin loss. Additionally, it appears to have a metastatic pattern that differs from the NST. This registry study aims to show clinical and pathological parameters in patients with early and advanced ILC.
Methods
Clinical and pathological data of 683 patients diagnosed with ILC were retrospectively collected and descriptively analyzed. Of these, 206 patients (30.2%) subsequently developed a local recurrence and/or distant metastasis.
Results
The majority of ILC patients presented with low Ki67, positive ER and PR, HER2-negativity and an intermediate grade tumor. E-cadherin loss was detected in 96.2% (n=427, 256 unknown). In summary, 0.4% of patients exhibited a pTis, 45.7% a pT1, 37.3% a pT2, 15.5% a pT3 and 1.1% a pT4 tumor (n=451, 26 unknown), while 68% of patients had pN0, 20.3% pN1, 7.3% pN2 and 4.3% pN3 status (n=438, 39 unknown). ILC tumors with a subsequent metastatic event initially showed similar data to non-metastatic tumors, although metastatic tumors have the highest rate in pT2 with 44.4% but 39.2% presented with pN0 in. Distant metastases were detected at the following sites: bones (43.7%; n=90), local recurrence (33.4%; n =69), peritoneum (12.6%; n=26), liver (11.2%; n=23), gynecological metastasis (10.7%; n=22) (multiple sites per person possible). Patients who progressed showed a slightly different profile, with a particular increase in cerebral lesions (24%, n=24).
Conclusions
This registry study summarizes histopathological data of ILC patients and shows a high rate of metastatic events despite initially good prognostic factors. The metastatic sites in this cohort resemble other studies and differ from NST in the frequency of visceral metastasis or metastasis inside the abdominal cavity (28.2%, n=58) in our cohort. This should be taken into consideration for planning surveillance for ILC patients in survivorship care.
Legal entity responsible for the study
AG Karsten-Speiser, Department of Gynecology with Breast Center, Charité - Universitätsmedizin Berlin.
Funding
Has not received any funding.
Disclosure
P. Jank: Financial Interests, Personal and Institutional, Stocks/Shares: Myriad Genetics Inc. M.M. Karsten: Financial Interests, Personal, Invited Speaker: Roche, Gilead, Sysmex. All other authors have declared no conflicts of interest.
72P - Correlation of serum cytokine patterns and clinicopathological factors in breast carcinoma patients (ID 291)
- Yoel Genaro Montoyo-Pujol (Alicante, Spain)
- Yoel Genaro Montoyo-Pujol (Alicante, Spain)
- Pascual Martínez-Peinado (Alicante, Spain)
- Sandra Pascual-García (Alicante, Spain)
- Ana Belén López-Jaén (Alicante, Spain)
- Jose Ponce (alicante, Spain)
- Inmaculada Lozano Cubo (Alicante, Spain)
- Bartomeu Massuti Sureda (Alicante, Spain)
- Elena Castellón-Molla (Alicante, Spain)
- Silvia Delgado (Alicante, Spain)
- Tina Aurora Martín-Bayón (Alicante, Spain)
- Hortensia Ballester (Alicante, Spain)
- Angela Ramos (Alicante, Spain)
- José Miguel Sempere-Ortells (Alicante, Spain)
- Gloria Peiro-Cabrera (Alicante, Spain)
Abstract
Background
Recent evidence support that the immune system has both positive and negative effects on tumorigenesis. Systemic inflammation has been linked to aggressive tumor growth, metastasis, and drug resistance in breast cancer (BC) patients. Therefore, serum cytokines (SC) may represent an exciting biomarker in the monitoring of BC pathogenesis.
Methods
Pretreatment serum from 204 BC patients (23% Luminal A, 23.6% Luminal B/HER2-, 22.5% Luminal B/HER2+, 10.3% HER2-enriched, and 20.6% Triple-Negative/Basal-like -TNBL-) and 50 healthy donors was collected. Measurement of 62 SC was performed using LEGENDplex immunoassay. Fluorescence intensity was quantified by flow cytometry. The results were correlated with age, tumor size and grade, vascular invasion, necrosis, phenotype, tumor-infiltrating lymphocytes, lymph node status, and Ki67. Statistical analysis was done by Student’s t-test and Mann–Whitney U test.
Results
BC patients showed higher levels of SCF, MIP3α, EPO and 4-1BB but lower levels of IL-2RA, IL-8, IL-12p40, IL-18, IL-23, IL-27, PDGF-AA, Galectin 9, PDGF-BB, B7.2, MIP1β and PD1, compared to the healthy group. Furthermore, IL-23, IL-27, and EPO correlated with younger age (p≤0.041), in contrast to Galectin 9, MCP1, IL-2RA, and MIP1β (p≤0.003). IL-12p40 and IFNγ were elevated in cases with grade I tumors (p≤0.05) and, in addition to IL-11 and IL-27 in low Ki67 tumors (p≤0.030). Moreover, IL-12p40 and IL-23 were associated with positive lymph nodes (p≤0.031). In Luminal tumors, we detected high IL-12p40, IL-15, IL-23, IL-27, and IFNγ (p≤0.048). However, only PDGF-BB was seen in non-Luminal tumor patients (p=0.040). IL-12p40, IL-18, IL-23, IL-27, SCF, and EPO were mainly higher in Luminal A, while PDGF-AA in Luminal B/HER2-. Likewise, MIP1β, MIP3α, and EPO were elevated in Luminal B/HER2+ serum, whereas Galectin9, PDGF-BB, IL-2RA, B7.2, SCF, 4-1BB, and PD1 were found in TNBL, with no specific profile for HER2-enriched.
Conclusions
Our results showed specific serum profiles of SC among BC phenotypes. Moreover, IL-12p40 and IL-23 were correlated with lymph node involvement in Luminal tumors, especially in Luminal A.
Legal entity responsible for the study
The authors.
Funding
Grant (SEAP-Proyecto Semilla; Expt. 200042); Biobank HGUA (21-154) and HUB-ICO-IDIBELL (PT17/0015/0024).
Disclosure
All authors have declared no conflicts of interest.
Q&A and discussion (ID 127)
- To be Announced (Barcelona, Spain)
- To be Announced (Barcelona, Spain)
Mentor (ID 492)
- Fabrice André (Villejuif, France)
- Fabrice André (Villejuif, France)
108P - Safety results of post-neoadjuvant T-DM1 in the Italian compassionate use program (GIM26-TRASTHER study). (ID 324)
- Francesca Poggio (Genova, Italy)
- Francesca Poggio (Genova, Italy)
- Marco Tagliamento (Genova, Italy)
- Diletta Favero (Genova, Italy)
- Michelino De Laurentiis (Napoli, Italy)
- Giuseppe Tonini (Rome, Italy)
- Antonio Bernardo (Pavia, Italy)
- Elisa Ferraris (Pavia, Italy)
- Ida Paris (Rome, Italy)
- Ferdinando Riccardi (Napoli, Italy)
- Giulia V. Bianchi (Milan, Italy)
- Giuseppe Cancello (Milan, Italy)
- Claudio Chini (Varese, Italy)
- Andrea Fontana (Pisa, Italy)
- Giancarlo Bisagni (Reggio Emilia, Italy)
- Alessandra Crippa (Lecco, Italy)
- Alessandra Gennari (Novara, Italy)
- Rossana Berardi (Torrette di Ancona, Italy)
- Antonino Musolino (Parma, Italy)
- Matteo Lambertini (Genova, Italy)
- Lucia Del Mastro (Genova, Italy)
Abstract
Background
T-DM1 is standard treatment in patients (pts) with HER2-positive breast cancer with residual disease after neoadjuvant therapy. The GIM26-TRASTHER study of the Gruppo Italiano Mammella (GIM) study group collects data from the Italian compassionate use program that anticipated drug reimbursement.
Methods
Inclusion criteria mirrored the Katherine trial. We registered adverse events (AEs) that were considered to be certainly/probably/possibly related to T-DM1 as per investigators’ judgement. We used descriptive analysis for data presentation.
Results
202 pts were included in 18 centers between Sep 2021 and Dec 2022. Median age was 52 years (IQR 45-59), 30% of the pts (n=61) were premenopausal and 56% (n=113) had at least 1 comorbidity (main: thyroid disorders 13%, hypertension 13%, dyslipidemia 4.5%). Smoking status was available for 156 pts, and 39 (25%) were current or former smokers. As neoadjuvant therapy, 85 % of the pts (n=169) received anthracycline plus taxane chemotherapy and 25 % (n=50) dual anti-HER2 blockade. Overall, 320 T-DM1-related AEs of any grade were registered in 105 pts (52%). G3 AEs were observed in 11 pts (5.4%), while there were no G4-G5 AEs. Most prevalent AEs of any grade were transaminases increase (19.8%), thrombocytopenia (15.3%), nausea and vomiting (13.3%), fatigue (10.9%), myalgia and arthralgia (7.4%), peripheral neuropathy (6.4%) and neutropenia (5%). For 42 out of 202 pts (20.8%), T-DM1 was reduced in dose, delayed or discontinued due to toxicity. Pts experiencing any grade AEs were older (54 vs 51, p=0.046), more frequently current or former smokers (34% vs 16.6%, p=0.034), and were less exposed to anthracyclines (79% vs 92%, p=0.012) as compared to those with no AEs. No impact of menopausal status, pre-existing comorbidities and type of neoadjuvant anti-HER2 therapy was observed.
Conclusions
In this multicentric Italian study, no new safety concerns of adjuvant T-DM1 were observed. Toxicity seems to be mostly linked by patient’s characteristics, underlying the importance of evaluating safety profile of anticancer drugs in a real-world setting in less selected pts. Further analyses, including survival outcomes, are ongoing.
Legal entity responsible for the study
GIM (Gruppo Italiano Mammella).
Funding
Roche.
Disclosure
F. Poggio: Financial Interests, Personal, Invited Speaker: Eli Lilly, Novartis, Pfizer; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Other: Daiichi Sankyo, Gilead. M. Tagliamento: Financial Interests, Personal, Other, travel grants: Roche, Bristol Myers Squibb; Financial Interests, Personal, Other: AstraZeneca; Financial Interests, Personal, Writing Engagements: Novartis, MSD, Amgen. M. De Laurentiis: Financial Interests, Personal, Advisory Board: Roche, Eli Lilly, Novartis, AstraZeneca, Seattle Genetics, Gilead, Ipsen, Takeda; Financial Interests, Personal, Research Grant: Puma Biotechnology, Macrogenics, Bristol Myers Squibb. A. Gennari: Financial Interests, Personal, Invited Speaker: Eisai, Novartis, Roche, Eli Lilly, Daiichi Sankyo, Gilead. M. Lambertini: Financial Interests, Personal, Advisory Board: Roche, Novartis, Eli Lilly, AstraZeneca, Gilead, MSD, Exact Science, Seattle Genetics; Financial Interests, Personal, Speaker’s Bureau: Takeda, Knight Terapeutics, Ipsen, Sandoz, Libbs; Financial Interests, Institutional, Research Grant: Gilead. L. Del Mastro: Financial Interests, Personal, Invited Speaker, Educational meeting: Novartis, Symposia, Andromeda E20, Vyvamed srl; Financial Interests, Personal, Invited Speaker, Lecture: Ipsen; Financial Interests, Personal, Advisory Board, Her2+ and TN breast cancer: Roche; Financial Interests, Personal, Invited Speaker, Consultancy for TNBC text: Roche; Financial Interests, Personal, Advisory Board, denosumab: Amgen; Financial Interests, Personal, Advisory Board, Early and metastatic BC: Eli Lilly; Financial Interests, Personal, Invited Speaker, CDK4-6 inhibitors: Eli Lilly; Financial Interests, Personal, Advisory Board, tucatinib: Seagen Int; Financial Interests, Personal, Advisory Board, Oncotype dx: Exact sciences, Havas life; Financial Interests, Personal, Advisory Board, Neratinib: Pierre Fabre; Financial Interests, Personal, Invited Speaker, Internal training: MSD; Financial Interests, Personal, Invited Speaker, Educational meetings: Accademia Nazionale Medicina; Financial Interests, Personal, Invited Speaker, Author for BC text: Pensiero Scientifico Editore; Financial Interests, Personal, Advisory Board, Breast cancer: Uvet; Financial Interests, Personal, Other, Author slide kits and interviews: Think2it; Financial Interests, Personal, Advisory Board, Palbociclib: Pfizer; Financial Interests, Personal, Invited Speaker, Breast cancer: Aristea, Meeting SrL; Financial Interests, Personal, Other, Author slide kits: Forum service; Financial Interests, Personal, Other, Author text about biosimilars: Edizioni Minerva Medica; Financial Interests, Personal, Other, consultant: Kardo srl; Financial Interests, Personal, Invited Speaker, Breast cancer meetings: Delphi international, Over srl; Financial Interests, Personal, Invited Speaker: Prex Srl, Editree; Financial Interests, Personal, Advisory Board: Uvet, Collage SpA, Daiichi Sankyo, AstraZeneca, Agendia, Gilead; Financial Interests, Personal, Other, Interview: Infomedica srl; Financial Interests, Personal, Other, Consultant: Sharing progress in cancer care - Switzerland; Financial Interests, Personal, Other, Consultancy: Eli lilly; Financial Interests, Institutional, Funding, National coordinating PI: Roche; Financial Interests, Institutional, Funding, Local PI: AstraZeneca, Roche, Eli Lilly, Daiichi Sankyo, Novella Clinical, Novartis; Non-Financial Interests, Institutional, Product Samples, Genomic Test: FoundationOne. All other authors have declared no conflicts of interest.
Back to work: What oncologists need to know and how they could help (ID 161)
- Agnes Dumas (Paris, France)
- Agnes Dumas (Paris, France)