Incorporating CDK4/6 Inhibitors in the Treatment of Advanced Luminal Breast Cancer

After optimizing endocrine monotherapy modalities in the setting of advanced luminal breast cancer (BC), dual endocrine/targeted therapy combinations have been tested with positive results, and are transforming this BC subtype treatment landscape. Cell cycle deregulation is a hallmark of cancer that has become a key druggable target in hormone receptor (HR)-positive BC due to its role in endocrine resistance mechanisms. Cyclin dependent kinase (CDK)4/6 inhibitors have experienced a fast development in combination with endocrine therapy and have already been commercialized in some countries. In this review, we will summarize the development of these CDK4/6 inhibitors in luminal BC, from the preclinical data to the pivotal phase III trials that led to their approval, focusing on the efficacy and safety data for each of the treatment settings. Moreover, we will consider the challenges CDK4/6 inhibitors face in their positioning in the algorithm of treatment for advanced luminal BC and the considerations physicians should take into account when selecting these therapies for their patients. However, we are still in need of reliable predictive biomarkers in order to identify patients who will derive the greatest benefit from these drug combinations that are not exempt from toxicity.