Abstract 13P
Background
In first-line metastatic HER2+ BC, the standard regimen of taxane-trastuzumab-pertuzumab (THP) is increasingly challenged by new therapies like antibody-drug conjugates. This shift accentuates the necessity for precise biomarkers to guide treatment decisions. Our study focuses on using HER2DX ERBB2 mRNA score to predict treatment responses and long-term prognosis, aiming to identify patients who would benefit more from escalation or de-escalation therapies.
Methods
We evaluated 85 patients with advanced HER2+ BC from Hospital Clinic of Barcelona, IOB-QuironSalud and Hospital Universitario 12 de Octubre, treated with the standard THP regimen between 2010 and 2024. HER2DX analysis was performed on formalin-fixed paraffin-embedded tumor samples. We correlated HER2DX ERBB2 mRNA score as a continuous variable and as pre-defined categories (low, medium, high) with progression-free survival (PFS) and overall survival (OS) using Cox regression models.
Results
The distribution of low, medium, and high HER2DX ERBB2 scores in our cohort was 16.5%, 23.5%, and 60.0%, respectively. With a median follow-up of 44.2 months (0.72-162.5), our cohort consisted of hormone receptor-positive cases (64.7%), patients with visceral disease (70.6%), brain metastasis (14.1%), and de novo metastatic disease (50.6%). Median PFS and OS to THP regimen were 27.1 and 62.7 months, respectively. HER2DX ERBB2 score was significantly associated with both PFS and OS, particularly in the ERRB2-high group, which showed significantly better PFS (28.6 vs. 12.5 months; hazard ratio=0.45, 0.26-0.78, p=0.005) and OS (not reached vs. 29.8 months; hazard ratio=0.23, 0.12-0.44, p<0.001). All patients without progression over 5 years and no death over 8 years (n=4) had ERBB2-high disease. These associations persisted in multivariable analyses.
Conclusions
The HER2DX ERBB2 mRNA score shows a significant association with improved survival in metastatic HER2+ BC patients treated initially with THP. Additional validation of the HER2DX ERBB2 score and integration of prognostic clinical factors might refine and optimize treatment strategies in this clinical setting.
Legal entity responsible for the study
The authors.
Funding
Reveal Genomics.
Disclosure
R. Sanchez Bayona: Financial Interests, Personal, Invited Speaker: Novartis, Lilly Oncology, GSK Oncology, AstraZeneca, Seagen, Clovis Oncology; Financial Interests, Personal, Other, Travel and accommodation: Pfizer; Financial Interests, Personal, Full or part-time Employment, Medical Advisor: SOLTI; Financial Interests, Personal, Full or part-time Employment, Scientific Secretary: SEOM - Spanish Society of Medical Oncology; Financial Interests, Personal, Other, Medical Monitor in HARMONIA Trial: Novartis. O. Martínez-Sáez: Financial Interests, Personal, Invited Speaker: Novartis, Eisai; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Other, Travel expenses: Roche; Financial Interests, Personal, Other, Medical advisory: Reveal Genomics. E. Segui Solis: Financial Interests, Personal, Invited Speaker: Novartis, Veracyte, Pfizer, Daiichi Sankyo, Eisai; Financial Interests, Personal, Advisory Board: Pfizer, Seagen; Financial Interests, Personal, Full or part-time Employment: SOLTI; Financial Interests, Personal, Research Grant: Amgen. P. Tolosa Ortega: Financial Interests, Personal, Invited Speaker: Novartis, Pfizer, Lilly, Seagen, AstraZeneca, Daiichi Sankyo and MSD; Financial Interests, Personal, Advisory Board: Novartis, Adamed, Seagen and Daiichi Sankyo; Financial Interests, Personal, Full or part-time Employment, Medical Advisor and Madical Monitor: SOLTI; Financial Interests, Institutional, Funding: Novartis. T. Pascual: Financial Interests, Personal, Invited Speaker: Pfizer/ AstraZeneca / Veracyte / Novartis; Financial Interests, Personal, Advisory Board: Roche/Genentech, Novartis. G. Villacampa Javierre: 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. W. Buckingham: Financial Interests, Institutional, Full or part-time Employment, Employed by Reveal Genomics SL: Reveal Genomics SL; Financial Interests, Personal, Stocks/Shares, Spouse stock ownership: Natera Inc. M. Marin: Financial Interests, Institutional, Full or part-time Employment, Product Manager: Reveal Genomics, S.L. 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: SOLTI; Financial Interests, Institutional, Other, Patent filed: EP23382703: Reveal Genomics S.L.; Financial Interests, Institutional, Other, Patent filed: EP23383369: Reveal Genomics S.L. P. Villagrasa Gonzalez: Financial Interests, Personal, Full or part-time Employment, CEO and co-founder of the company: Reveal Genomics S.L.; Financial Interests, Personal, Ownership Interest: Reveal Genomics S.L.; Financial Interests, Personal, Royalties, PCT/EP2021/086493 - In Vitro Method For The Prognosis Of Patients Suffering From Her2-Positive Breast Cancer: Reveal Genomics S.L. C.M. Perou: Financial Interests, Personal, Other, consultant: GeneCentric Therapeutics, Bioclassifier LLC, Reveal Genomics; Financial Interests, Personal, Member of Board of Directors: GeneCentric Therapeutics; Financial Interests, Personal, Ownership Interest: GeneCentric Therapeutics, Bioclassifier LLC, Reveal Genomics; Financial Interests, Personal, Royalties: Bioclassifier LLC. A. Prat: Financial Interests, Personal, Invited Speaker: Roche, 1TRIALSP, S.L.; 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, Member of Board of Directors, Leadership role: Reveal Genomics, SL.; Financial Interests, Personal, Stocks/Shares: Reveal Genomics, Oncolytics Biotech; Financial Interests, Personal, Royalties: Reveal Genomics, International Oncology Bureau, S.L.,; 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. F. Brasó-Maristany: Financial Interests, Personal, Full or part-time Employment, part time employment: Reveal Genomics SL; Financial Interests, Personal, Other, Patents filed: EP23382703 and EP23383369: Reveal Genomics SL; Financial Interests, Personal, Other, Patents filed: PCT/EP2022/086493, PCT/EP2023/060810: Fundació de Recerca Clínic Barcelona-Institut d'Investigacions Biomèdiques August Pi i Sunyer. E.M. Ciruelos: Financial Interests, Personal, Other, Speakers Bureau. Educational activities: Roche; Financial Interests, Personal, Invited Speaker, Symposia and Educational activities: Roche; Financial Interests, Personal, Advisory Board, Non-permanent advisor: Roche, Lilly, Novartis, Pfizer, Daiichi Sankyo, MSD; Financial Interests, Personal, Invited Speaker, Symposia and Education: Lilly; Financial Interests, Personal, Invited Speaker, Educational activities: Pfizer; Financial Interests, Personal, Advisory Board, Non-permanent advisor, Travel accommodation: AstraZeneca; Financial Interests, Personal, Other, Advisory Board: Gilead; Financial Interests, Personal, Other, Advisory Board, Invited speaker: Seagen; Financial Interests, Institutional, Funding, PI for Patricia 2 trial (sponsor: SOLTI Group): Pfizer; Financial Interests, Institutional, Funding, PI for Prometeo 2 trial (sponsor: SOLTI Group): Pfizer; Financial Interests, Institutional, Funding, PI for TATEN trial (sponsor: SOLTI Group): MSD; Financial Interests, Institutional, Funding, PI for ATREZZO trial (sponsor: SOLTI Group): Roche; Non-Financial Interests, Member of Board of Directors, Non-profit organization dedicated to breast cancer research: SOLTI Cooperative Group; Non-Financial Interests, Advisory Role, Scientific Evaluator at ISCIII (Spanish Government Academic Research Platform): Instituto de Salud Carlos III. All other authors have declared no conflicts of interest.