Histomorphological and Immunohistochemical Features of Breast Tumors in Patients with BRCA1 and BRCA2 Mutations: An Integrative Literature Review
DOI:
https://doi.org/10.66201/ss.v1.15Keywords:
Hereditary Breast Cancer, BRCA1, BRCA2, Histopathology, Immunohistochemistry, Homologous Recombination Deficiency, Tumor-Infiltrating Lymphocytes, PD-L1, PARP Inhibitors, Integrative ReviewAbstract
Background: Hereditary breast cancer, associated with germline BRCA1 and BRCA2 mutations produces distinct tumor phenotypes due to its differentiated molecular functions in DNA repair. Despite advances in precision oncology, evidence on differentiated histomorphological and immunohistochemical profiles was fragmented. This review seeks to integrate and compare these characteristics to synthesize their therapeutic implications.
Methods: An integrative literature review (Whittemore and Knafl framework) was conducted by searching four databases (2018–2026). Eighteen high-quality studies (clinical trials, cohorts, meta-analyses), comprising more than 14,000 participants, were selected to generate a comprehensive understanding of histopathological profiles.
Results: BRCA1 tumors are predominantly aggressive, Grade III (55–75%), with a medullary or pushing-edge morphology, and a Triple Negative phenotype (TNBC, 71.1%). They exhibit high proliferation (Ki-67 ≥ 30%) and a unique immunogenic microenvironment with PD-L1/PD-1 overexpression and a T cell-inflamed signature. BRCA2 tumors are mainly luminal (ER+ in 65–77%) with a lower degree, lower proliferation (Ki-67 ≥ 30% in 58.2%), and lack the immunogenic profile of BRCA1. Both subtypes respond to carboplatin in the metastatic context and to adjuvant olaparib.
Conclusions: BRCA1 and BRCA2 phenotypes represent biologically distinct subtypes of homologous recombination deficiency. Profile recognition of BRCA1 (TNBC, Grade III, PD-L1+) is crucial for therapeutic stratification: while BRCA1 is a candidate for platinum, PARP inhibitors and potential immunotherapies, BRCA2 focuses on endocrine therapy with PARP inhibitors.
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Copyright (c) 2026 Jamile Freitas Ribeiro, Alice Vittoria Steirnagel, Raissa Alvarenga Oliva, Isabelli Müller Betine, Juliana Januário Aguiar, Lucas Gesser Chagas, Eleandro Camargo, Leandro Dos Santos Dantas, Natália Camily De Sousa Orso, João Manoel Gomes Ferreira, Andrea Paola Britos Gómez (Autor/a)
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