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Endocrine therapy and cyclin-dependent kinase (CDK) inhibitor therapy

Source: Breast Cancer Treatment (PDQ®)–Health Professional Version, National Cancer Institute.

Source updated: April 25, 2025 · Captured 2026-09-09.

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Context: Treatment of Metastatic Breast Cancer / Metastatic HER2-Negative Hormone Receptor–Positive Breast Cancer

CDK4 and CDK6 have been implicated in the continued proliferation of hormone receptor–positive breast cancer resistant to endocrine therapy. CDK inhibitors have been approved by the U.S. Food and Drug Administration (FDA) in combination with endocrine therapy in both first-line and later-line treatment of advanced, HER2-negative hormone receptor–positive breast cancer. Three oral CDK4/6 inhibitors are currently available: palbociclib, ribociclib, and abemaciclib.

Overall, the addition of CDK4/6 inhibitors to endocrine therapy is associated with improved breast cancer outcomes and, in general, either maintained or improved quality of life.[3-8] This benefit was observed across multiple clinicopathological subgroups of breast cancer.[9]

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First-line palbociclib and endocrine therapy →First-line ribociclib and endocrine therapy →First-line abemaciclib and endocrine therapy →Second-line palbociclib and endocrine therapy →Second-line ribociclib and endocrine therapy →Second-line abemaciclib and endocrine therapy →CDK inhibitor therapy after disease progression on a prior CDK inhibitor →Single-agent CDK inhibitor therapy →

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