Several phase III clinical trials demonstrated the efficacy of PARPi in ER+/HER2- in early and mBC associated with germline BRCA mutation, especially in those with high-risk features characterized by bulky diseases and residual cancer cells after neo-adjuvant chemotherapy in localized BC, and early disease progression during treatment with CDK4/6 inhibitor in mBC. The gene discussed is CDK4; the disease is breast cancer.