Selective oestrogen receptor degraders in breast cancer: a review and perspectives

Abstract

Purpose of review: Estrogen receptor-positive breast cancer accounts for 70% of all breast cancers. Sequential endocrine treatment in monotherapy or in combination with CDK 4/6 or m-TOR inhibitors is the mainstay of recommended treatment options in the management of metastatic breast cancer even in the presence of visceral metastasis. There is an emerging need to address endocrine resistance, which despite highly efficacious treatment combinations still can develop.

Recent findings: One of the mechanisms of endocrine resistance is molecular alteration of the oestrogen receptor itself, such as ESR1 mutations affecting the ligand-binding domain. These mutations emerge under the selective pressure of aromatase inhibitors. The efficacy of selective oestrogen receptor degraders (SERDs) might not be affected by the presence of molecular alterations of oestrogen receptor. Fulvestrant is the only SERD used in current clinical practice. Numerous novel, nonsteroidal orally available SERDs are currently in clinical development. Efficacious oestrogen receptor target engagement and promising clinical activity was shown in early phase clinical trials.

Summary: Therefore, a new class of orally available nonsteroidal SERDs gains high interest in tackling endocrine resistance in oestrogen receptor-positive (ER+) advanced breast cancer. Clinical efficacy needs to be confirmed in larger patient populations.