Amid expanding evidence that vitamin D deficiency can negatively affect response for patients with hormone receptor (HR)–positive breast cancer undergoing CDK4/6 inhibitor treatment, we are seeking to demonstrate the importance of standardizing supplementation of this essential vitamin. In vitro and in vivo research has shown anticancer effects of vitamin D, and small studies have suggested that combining vitamin D with CDK4/6 inhibitors may increase treatment effectiveness. Both of these agents work to inhibit cell cycle progression, so there could be additive effects on cell cycle arrest.
Also, vitamin D might help reverse cancer drug resistance, which is a significant challenge in CDK inhibitor therapy. Correcting deficiency may be beneficial, especially since some groups have been found to have up to an 80% deficiency rate for this essential vitamin. Short term we seek to raise awareness of the issue of vitamin D deficiency in breast cancer and long term to demonstrate the efficacy of a vitamin D supplementation program in the setting of adjuvant or metastatic breast cancer being treated with CDK4/6 inhibitors.
Our hypothesis is that correcting vitamin D deficiency will have beneficial effects on response to hormonal therapy plus CDK4/6 inhibitors and may lessen adverse effects. We are starting to review cases of metastatic HR-positive breast cancer with either short-term or no response to CDK4/6 inhibitors to look for factors in common, such as clinical characteristics, ethnicity, and vitamin D levels. We then plan to correct vitamin D deficiency aggressively in a prospective group of patients and to compare the response rates and progression-free survival with the many published trials with these agents.
