Clinical Management in BRCA Carriers with Early Breast Cancer

Muñante B.; Paz-Manrique R.; Pinto J.A.; Gomez H.L. · Cancer Control (2025) · DOI: 10.1177/10732748251377864

Resumen

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. © The Author(s) 2025. This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).

Instituciones: Universidad Peruana Cayetano Heredia; Universidad San Ignacio de Loyola; Universidad Privada San Juan Bautista