Concurrent Use of Cyclin Dependent Kinase 4/6 (CDK4/6) Inhibitors with Palliative Radiotherapy for Metastatic Breast Cancer Patients: A Review of Toxicity

Breast cancer remains to be the most common cancer in women. Given the recent developments in oncology, while more women with early breast cancer are being cured, patients with metastatic breast cancer are living longer. There have been improvements in the treatment of hormone-sensitive metastatic breast cancer by the addition of CDK 4/6 inhibitors to endocrine treatment. CDK 4 and CDK 6 control entry into the cell cycle via estrogen signaling pathway and their inhibition was shown to prevent tumor cell cycle progression. Three CDK4/6 inhibitors available for hormone receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer are palbociclib, ribociclib, and abemaciclib. CDK 4/6 inhibitors are suggested as radiosensitizers given their mechanism of action that inhibits cell cycle progression as well as DNA repair. However, there are concerns regarding their concurrent use with radiotherapy given their potential to delay normal tissue repair. Currently, there are several retrospective series suggesting a site-dependent toxicity. After reviewing preclinical and retrospective studies, we suggest further studies are required to clarify the safety of this combination. Until then, oncologists should evaluate each case with caution regarding the potential risks of CDK 4/6 inhibitors in combination with radiotherapy.

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