BRCA1 and neoplasm: The synergy with endocrine therapy (Exemestane) is mechanistically plausible because PARPi-induced DNA damage may impair the ER pathway, and ER blockade can downregulate critical DNA repair genes (e.g., BRCA1, RAD51), together creating a “dual hit” that exacerbates genomic instability and enhances tumor cell death in HR + disease (Sottnik et al., 2025; Wu et al., 2020).