How I treat endocrine-dependent metastatic breast cancer

Abstract

Estrogen receptor-positive (ER+)/HER2-negative (HER2-), the so-called luminal-type breast cancer, is the most frequent subset, accounting for around 70% of all breast cancer cases. Endocrine therapy (ET) combined with cyclin-dependent kinases (CDK) 4/6 inhibitors is the standard first option in the management of advanced luminal breast cancer independently of disease extension. Classically, patients undergo multiple lines of ET ± targeted treatments until endocrine resistance occurs and palliative chemotherapy is proposed. Understanding endocrine resistance mechanisms and development of novel ET options is one of the main challenges in current clinical research. Another area of utmost interest is the improvement of post-endocrine therapeutic approaches. Among others, the development of antibody-drug conjugates (ADCs) is very promising, and some of these drugs will probably soon become a part of the therapeutic arsenal against this incurable disease. This review paper provides an overview of currently available treatment options in ER+/HER2- metastatic breast cancer and extensively discusses new approaches in late clinical development.

Keywords: CDK 4/6; PIK3CA; SERD; antibody–drug conjugate (ADC); luminal breast cancer.

Figure 1

Treatment algorithm of estrogen receptor-positive/HER2-negative advanced breast cancer. AI, aromatase inhibitor; ctDNA, circulating tumor DNA; DFI, disease-free interval; ER, estrogen receptor; ESR-1, gene encoding estrogen receptor-α; ET, endocrine therapy; HER2, human epidermal growth factor receptor 2; MBC, metastatic breast cancer; NGS, next-generation sequencing; NSAI, non-steroidal aromatase inhibitor; SERD, selective estrogen receptor degrader; BRCA, BReast CAncer gene; wt, wild-type; PIK3CA, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha; CDK 4/6, cyclin-dependent kinase 4 and 6.