March 3, 2026Open Access

BRCA and CDK4/6: allies or antagonists?—efficacy of CDK4/6 inhibitors in HR+/HER2− breast cancer with germline BRCA1/2 mutations: a narrative review

Key Points

Evidence suggests routine brca testing informs treatment choices for hr+/her2- breast cancer with cdk4/6 inhibitors and parp inhibitors, enhancing outcomes.
Prioritization of therapeutic sequencing for patients with brca mutations shows promise, particularly in high-risk settings, driving future research.
Analysis emphasizes the need for biomarker-driven strategies to optimize results in treating hr+/her2- breast cancer with cdk4/6 inhibitors.
Calls for clinical guidelines improvements highlight the critical role of understanding resistance mechanisms for brca-mutated breast cancer.

Abstract

This review underscores the need for prospective studies to clarify the prognostic and predictive role of gBRCAm in CDK4/6i-treated HR+/HER2- BC. Current evidence supports routine BRCA testing to inform therapeutic sequencing, with poly(ADP-ribose) polymerase inhibitors (PARPis) prioritized in high-risk early-stage and metastatic settings. Future research should focus on biomarker-driven strategies, including combinations to optimize outcomes. These insights may refine clinical guidelines, advocate for personalized treatment algorithms, and stimulate research into resistance mechanisms, ultimately improving care for BRCA-mutated BC patients.

BRCA and CDK4/6: allies or antagonists?—efficacy of CDK4/6 inhibitors in HR+/HER2− breast cancer with germline BRCA1/2 mutations: a narrative review

Key Points

Abstract

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