Homologous recombination pathway alterations in basal-like breast cancer.

Breast cancer is a heterogeneous disease comprising multiple molecular subtypes with distinct biological and clinical features. Among them, the basal-like subtype accounts for approximately 15-20% of cases and is associated with poor prognosis. Basal-like breast cancers (BLBC) share several histo-molecular characteristics with BRCA1-deficient tumors, including genomic instability and reduced BRCA1 expression beyond germline-mutated cases, suggesting potential alterations in homologous recombination (HR) DNA repair. These observations have led to the hypothesis that homologous recombination deficiency (HRD) may be enriched in a subset of BLBC. However, the extent, causes, and clinical implications of HRD in this subtype remain incompletely defined, as much of the available evidence is derived from triple-negative breast cancer (TNBC) cohorts, which only partially overlap with BLBC. In this review, we first summarize the transcriptomic definition of BLBC and its relationship to TNBC. We then provide a concise overview of current HRD detection methods, followed by a critical analysis of their application specifically to basal-like tumors. We next examine the molecular mechanisms that may contribute to HRD in BLBC, distinguishing well-supported alterations from emerging mechanisms. Finally, we discuss the therapeutic implications of HRD in BLBC, highlighting current limitations of clinical evidence and the challenges of translating a biologically defined subtype into a clinically actionable framework. Overall, while a BLBC-centered approach may offer a more biologically homogeneous context to study HRD, its clinical relevance remains to be established, and future studies specifically designed in molecularly defined cohorts will be required to clarify its diagnostic and therapeutic value.