Journal Article

Clinical Management in BRCA Carriers with Early Breast Cancer

Muñante, Bruno, Gomez, Henry L., Paz-Manrique, Roberto, Pinto, Joseph A.

2025

Overview

Background Breast cancer remains a leading cause of cancer-related morbidity and mortality globally, with BRCA1/2 mutation carriers facing distinct challenges due to aggressive tumor biology and heightened risks of contralateral and secondary cancers. Purpose This review synthesizes evidence on managing early-stage breast cancer in BRCA mutation carriers, emphasizing Latin America’s heterogeneous BRCA prevalence (ranging from 5% to 25.7% across countries), which underscores the need for region-specific genetic screening. BRCA-associated tumors exhibit homologous recombination deficiency, informing therapeutic strategies such as PARP inhibitors, which exploit synthetic lethality, as demonstrated by the OlympiA trial showing Olaparib’s sustained survival benefits (28% reduction in mortality risk). Imaging strategies must adapt to BRCA-related tumor phenotypes: BRCA1 carriers often present mammography-elusive tumors, favoring MRI, while abbreviated MRI protocols offer cost-effective alternatives without compromising sensitivity. Surgical decision-making balances breast-conserving surgery (BCS) and mastectomy, with studies showing comparable survival outcomes but elevated contralateral cancer risk post-BCS (10-year risk: 14%), necessitating vigilant surveillance. Contralateral prophylactic mastectomy reduces contralateral cancer risk but requires personalized risk-benefit discussions. Neoadjuvant platinum-based chemotherapy shows higher pathologic complete response rates in BRCA carriers, particularly in triple-negative subtypes, though adjuvant platinum benefits remain under investigation. Emerging immunotherapies, such as pembrolizumab in KEYNOTE-522, show promise but lack BRCA-specific efficacy data. Special considerations for transgender BRCA carriers highlight evolving screening guidelines, including mammography for hormonally treated transgender women and multimodal imaging for non-mastectomized transgender men. Conclusions Optimizing outcomes for BRCA mutation carriers demands multidisciplinary, personalized approaches integrating genetic, regional, and clinical factors. Advances in targeted therapies, refined imaging, and risk-adapted surgery emphasize the importance of shared decision-making and ongoing research to address knowledge gaps in survivorship and equitable care.

• Publisher: SAGE Publications,Sage Publications Ltd,SAGE Publishing
• Subject: BRCA1 protein / BRCA1 Protein - genetics / BRCA2 Protein - genetics / Breast cancer / Breast Neoplasms - diagnosis / Breast Neoplasms - genetics / Breast Neoplasms - pathology / Breast Neoplasms - therapy / Chemotherapy / Decision making / Female / Genetic screening / Homologous recombination / Humans / Immunotherapy / Lethality / Magnetic resonance imaging / Mammography / Mastectomy / Morbidity / Mortality / Mutation / Pembrolizumab / Phenotypes / Platinum / Surgery / Survival / Transgender persons / Tumors