Circulating Biomarkers of CDK4/6 Inhibitors Response in Hormone Receptor Positive and HER2 Negative Breast Cancer

SIMPLE SUMMARY: Biomarkers found in the blood of patients with hormone receptor positive and HER2 negative metastatic breast cancer are being investigated to understand how patients respond to treatments. Circulating biomarkers have the potential advantage of giving important information with a simple withdrawal of peripheral blood. Here, we review and discuss the recent achievements in the development of circulating biomarkers in patients with metastatic breast cancer treated with CDK4/6 inhibitors and endocrine therapy. ABSTRACT: CDK4/6 inhibitors (CDK4/6i) and endocrine therapy are the standard treatment for patients with hormone receptor-positive and HER2 negative (HR+/HER2−) metastatic breast cancer. Patients might show intrinsic and acquired resistance, which leads to treatment failure and progression. Circulating biomarkers have the potential advantages of recognizing patients who might not respond to treatment, monitoring treatment effects and identifying markers of acquired resistance during tumor progression with a simple withdrawal of peripheral blood. Genomic alterations on circulating tumor DNA and serum thymidine kinase activity, but also circulating tumor cells, epigenetic or exosome markers are currently being tested as markers of CDK4/6i treatment response, even though none of these have been integrated into clinical practice. In this review, we discuss the recent advancements in the development of circulating biomarkers of CDK4/6i response in patients with HR+/HER2−breast cancer.