Endocrine combination therapies in locally advanced and metastatic breast cancer—combination therapy better than monotherapy

Abstract

Endocrine therapy for hormone receptor-positive locally advanced or metastatic breast cancer has undergone significant changes in the past few years. New substances have been developed to overcome endocrine resistance and well-known drugs are combined with new substances. The group of CDK (cyclin-dependent kinase) 4/6 inhibitors has proven its superiority over endocrine monotherapy but new substances such as the PI3K (phosphoinositide 3‑kinase inhibitor) inhibitor alpelisib offer new therapeutic options for patients with PIK3CA-mutated breast cancer. The combination of everolimus, an mTOR (mechanistic target of rapamycin) inhibitor, and exemestane is still relevant in the treatment of metastatic breast cancer. Endocrine combination therapies have become indispensable in clinical practice and have led to a significantly better prognosis and partly proven prolonged survival for patients. Further research is needed to discover the optimal therapeutic sequence and combinations of therapies as well as to examine mechanisms of endocrine resistance to overcome these. For this purpose, triplet combinations should be considered in the future.