Abstract PS5-04-21: Impact of Germline BCRA variants in the neoadjuvant treatment

Abstract Background: Carriers of pathogenic BRCA1 and BRCA2 variants often develop breast cancers with distinct pathological features, frequently associated with more aggressive phenotypes such as triple-negative tumors. Previous studies have reported greater benefit from neoadjuvant chemotherapy and higher rates of pathological complete response in this population. Objective: To evaluate the response to neoadjuvant therapy and survival outcomes in breast cancer patients with germline BRCA1/2 variants compared with those with wild-type phenotypes. Methods: Women ≤45 years with breast cancer were included in the hereditary cancer protocol at INEN between 2013 and 2020. Genetic testing was performed at the City of Hope (COH). We selected patients who had received neoadjuvant treatment. Results: A total of 105 patients were analyzed, including 45 with germline BRCA1/2 variants and 60 wild-type. Most patients received standard chemotherapy with anthracyclines and weekly taxanes (85%), while only a minority (12%) had access to carboplatin due to policy and approval restrictions. The median age was 40 years and comparable between groups, as all participants belonged to the hereditary breast cancer screening program. No significant differences were observed in pathological complete response (pCR) between BRCA variant carriers and wild-type patients, although a correlation was noted between pCR and the triple-negative subtype (p=0.053). In terms of survival, BRCA1 carriers showed poorer outcomes, with a hazard ratio of 2.5 and a median overall survival of 6.9 years, while BRCA2 carriers had a median survival of 11.6 years, comparable to wild-type patients whose median survival has not yet been reached. It is likely that the suboptimal pCR rates in BRCA mutation carriers were influenced by the limited use of carboplatin, a drug shown in other studies to significantly improve response rates. Conclusions: In this cohort of 105 breast cancer patients, BRCA1 carriers had worse overall survival (median 6.9 years, HR 2.5) compared with BRCA2 and wild-type patients, despite similar pCR rates. Pathological complete response was mainly associated with the triple-negative subtype. Limited access to carboplatin likely contributed to suboptimal responses in BRCA mutation carriers, underscoring the need for broader availability of platinum-based therapy. Citation Format: N. Valdiviezo, I. Otoya, P. Mora, J. Herzog, L. Reynaga, S. Neciosup, C. Calle, S. Casavilca, K. Roque, Z. Morante, H. Fuentes, C. Castañeda, T. Vidaurre, V. Acuña, M. Falla, J. Galarreta, S. Gruber. Impact of Germline BCRA variants in the neoadjuvant treatment abstract. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS5-04-21.