Endocrine Therapy: From Ovarian Ablation to Individualized Therapy and Signal Inhibition

At the end of the 19th century, Sir George Thomas Beatson first discovered the positive influence of a bilateral oophorectomy on the development of breast cancer lesions in women with advanced disease. Since then, endocrine therapy has been a key component of the treatment of both early (EBC) and advanced-stage (MBC) hormone receptor (HR)-positive breast cancer.

This review discusses the evolution of this therapeutic approach from the introduction of high-dose estrogen therapy leading to the development of several antiestrogen therapies. Recently, the new generation of drugs includes selective estrogen receptor modulators, orally administered selective estrogen receptor degraders (SERDs), as well as more unique agents such as complete estrogen receptor antagonists, proteolysis targeting chimeric, and selective estrogen receptor covalent antagonists. These drugs are under evaluation in various levels of randomized clinical trials (RCTs) being evaluated in both early and metastatic settings. As of today, the options in EBC are ranging from short-term neoadjuvant endocrine therapy to monitor the responsiveness of Ki-67 to combined endocrine therapy in MBC, introducing the combination of endocrine therapy and CDK4/6 inhibition as well as PARP inhibition in patients with luminal breast cancer presenting with germline BRCA1/2 mutations. The results of global RCTs are settled in global and local guidelines to optimize the individual therapy of our patients with luminal EBC.

Endocrine intervention in hormone-sensitive breast cancer remains one of the most important options in all settings of early and metastatic breast cancer.