Association between chemotherapy use and clinical outcomes in young BRCA carriers with T1N0 breast cancer: Results from an international cohort study.
Year: 2025
Type: conference-abstract
Abstract: 541 Background: Systemic treatment decisions for young BRCA carriers with small node-negative breast cancers present unique challenges due to limited evidence on the benefits of chemotherapy in this setting. This study evaluated chemotherapy use and survival outcomes among these patients. Methods: The BRCA BCY collaboration (NCT03673306) is an international, multicenter, hospital-based, retrospective cohort study that included carriers of germline pathogenic variants in BRCA1/2 diagnosed with invasive breast cancer at the age of ≤40 years between January 2000 and December 2020. Among patients diagnosed with T1N0 disease, survival outcomes - disease-free survival (DFS) and overall survival (OS) defined from breast cancer diagnosis - were compared between patients who received chemotherapy and those who did not, using multivariate Cox models adjusted for propensity score (including age at diagnosis, histology, grade, country and year of diagnosis) and risk-reducing surgeries (bilateral risk-reducing mastectomy (RRM) and/or risk-reducing salpingo-oophorectomy (RRSO)), and accounting for the delayed entry at the time of BRCA testing (i.e. left truncation). Subgroup analyses were performed according to tumor subtype (HR+/HER2- vs triple negative breast cancer (TNBC)). Results: Out of 5660 from 109 centers, 1280 patients had T1N0 breast cancer: T1mic (n = 14, 1.1%), T1a (n = 92, 7.2%), T1b (n = 303, 23.7%), T1c (n = 778, 60.8%), and T1 size unknown (n = 93, 7.3%). Most patients received chemotherapy (80%), although use was less frequent over time. Among patients who received chemotherapy, the majority were treated with an anthracycline-containing regimen (83.6%) and in the adjuvant setting (85.7%). Patients who received chemotherapy were younger and more likely to have high grade, TNBC or larger tumors compared to those who did not. The median follow-up was 8.7 years (IQR 5.0-13.4 years), during which 428 had DFS events including second primary breast cancer (n = 174), locoregional (n = 130), distant relapse (n = 65), second primary non breast cancer (n = 53), and 88 had died. Overall, 8-year DFS was 69.4%. In multivariate analysis, no significant differences in DFS or OS were observed between patients who received chemotherapy and those who did not (DFS HR = 0.92, 95% CI 0.65-1.31; OS HR = 0.68, 95% CI 0.37-1.24). No significant difference in 8-year DFS was observed between patients with HR+/HER2- breast cancer (n = 474) treated with or without chemotherapy (HR 0.91: 95% CI 0.59-1.43), or between patients with TNBC (n = 637) treated with or without chemotherapy (HR 0.84: 95% CI 0.46-1.53). Conclusions: In this global study of young BRCA carriers with T1N0 breast cancer, chemotherapy was not associated with better DFS or OS overall. However, these patients remain at high risk of events and warrant investigation of additional risk-reduction strategies.
Source: Journal of Clinical Oncology
Authors: Filipa Lynce, Eva Blondeaux, Virginia Delucchi, Hee Jeong Kim, Rinat Bernstein-Molho, Sabine C. Linn, Florence Coussy, Antonio Di Meglio, Kelly-Anne Phillips, Ava Kwong, Hans Wildiers, Elisa Agostinetto, Robert Fruscio, Alberta Ferrari, Laura De Marchis, Carmen Criscitiello, Katarzyna Pogoda, Meredith M. Regan, Ann H. Partridge, Matteo Lambertini
Institutions: Dana-Farber Cancer Institute, Ospedale Policlinico San Martino, University of Genoa, Asan Medical Center, University of Ulsan, Tel Aviv University, The Netherlands Cancer Institute, Université Paris Cité, Institut Curie, Inserm, Institut Gustave Roussy, Fondation Gustave Roussy, Peter MacCallum Cancer Centre, University of Hong Kong, Universitair Ziekenhuis Leuven, Université Libre de Bruxelles, Institut Jules Bordet, University of Milan, Policlinico San Matteo Fondazione, Policlinico Umberto I, Sapienza University of Rome, European Institute of Oncology, The Maria Sklodowska-Curie National Research Institute of Oncology, Harvard University
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: bronze
OpenAlex ID: W4410809075