Rinat Bernstein-Molho, Tal Sella, Virginia Delucchi, Florence Coussy, Hee Jeong Kim, Sabine Linn, Antonio Di Meglio, Katarzyna Pogoda, Ava Kwong, Elisa Agostinetto, Jyoti Bajpai, Yannick Van Herck, Alberta Ferrari, Judith Balmana, Halle C F Moore, Fedro A Peccatori, Ann H Partridge, Melina Winocur, Tiphaine Renaud, Christine Rousset-Jablonski, Jeong Eon Lee, Angela Toss, Shani Paluch-Shimon, Stephanie M Wong, Alexios Matikas, Cynthia Villarreal-Garza, Claudio Vernieri, Minna Lee, Deniz Can Guven, Wanda Cui, Kathryn J Ruddy, Maria Vittoria Dieci, Robert Fruscio, Laura De Marchis, Zoe Kemp, Pedro A Meireles, Maria Grazia Razeti, Maria Del Pilar Diz, Shelley E Hwang, Fabio Puglisi, Florian Clatot, Rinat Yerushalmi, Natalia Cichowska-Cwalinska, Alessandra Chirco, Carmine De Angelis, Eva Blondeaux, Matteo Lambertini
In young BRCA carriers with HER2-negative early BC, no statistically significant differences in survival outcomes were detected across different chemotherapy regimens. Our findings may inform future prospective studies evaluating chemotherapy de-escalation strategies in this genetically defined population.
BACKGROUND: Evidence to guide (neo)adjuvant chemotherapy choices in carriers of germline BRCA1/BRCA2 pathogenic variants (BRCA carriers) with early breast cancer (BC) is limited. We evaluated the association of different chemotherapy regimens with survival outcomes in this population.
METHODS: The BRCA BCY Collaboration (NCT03673306) is an international, multicenter, retrospective cohort study of BRCA carriers diagnosed with stage I-III BC at age ≤ 40 years, between 2000 and 2020. Disease-free survival (DFS) and overall survival (OS) were assessed among patients with HER2-negative disease treated with anthracycline-taxane, anthracycline-no-taxane, or non-anthracycline (neo)adjuvant chemotherapy. The association of platinum use with outcomes was evaluated in triple-negative breast cancer (TNBC).
RESULTS: Among 4200 young BRCA carriers from 109 centres who received (neo)adjuvant chemotherapy for HER2-negative BC, 58.7% had TNBC. Median follow-up was 8.1 years (IQR, 4.7-12.6 years). Anthracycline-taxane, anthracycline-no-taxane, and non-anthracycline regimens were used in 74.4%, 19.3%, and 6.3% of patients, respectively. Platinum agents were administered in 19.8% of TNBC cases. After multivariable adjustment, no significant differences in DFS or OS were observed between anthracycline-no-taxane and anthracycline-taxane regimens (DFS adjusted hazard ratio [aHR] 0.88, 95% CI 0.73-1.05; OS aHR 1.20, 95% CI 0.87-1.67) or non-anthracycline regimens (DFS aHR 1.07, 95% CI 0.82-1.38; OS aHR 1.16, 95% CI 0.68-2.0). In TNBC, platinum use was not associated with improved outcomes.
CONCLUSIONS: In young BRCA carriers with HER2-negative early BC, no statistically significant differences in survival outcomes were detected across different chemotherapy regimens. Our findings may inform future prospective studies evaluating chemotherapy de-escalation strategies in this genetically defined population.