Long-term management of patients with hormone receptor-positive metastatic breast cancer: Concepts for sequential and combination endocrine-based therapies.

Treatment options for hormone receptor-positive (HR-positive) metastatic breast cancer (MBC) continue to increase in parallel with expanding knowledge about the complex biology of breast cancer subtypes and resistance mechanisms to endocrine therapy. For patients with HR-positive MBC, there are now an unprecedented number of endocrine-based treatment options that can improve long-term outcomes, while preserving or optimizing quality of life, and that can be used before selecting more cytotoxic chemotherapeutic regimens. In addition to antiestrogens, steroidal and nonsteroidal aromatase inhibitors, the selective estrogen-receptor degrader, fulvestrant, and new endocrine-based combinations provide significant and clinically meaningful improvements in outcomes in the first line setting and beyond. Also, new clinical scenarios and indications for monotherapy endocrine and targeted therapies continue to be explored. Patients have several therapeutic options when their disease progresses or becomes resistant, although the optimal sequencing of these therapies remains unclear. Ongoing research in the resistant/refractory setting is anticipated to continue improving the outlook for these patients. This review will discuss current and investigational approaches to sequential single-agent endocrine and endocrine-based combination therapy for the long-term management of patients with HR-positive, human epidermal growth factor receptor 2-negative MBC.