Optimal treatment strategies in postmenopausal women with hormone-receptor-positive and HER2-negative metastatic breast cancer

Metastatic breast cancer (MBC) is unfortunately still considered incurable; treatment aims to prolong progression-free and overall survival, relieve disease symptoms, and maintain quality of life. Treatment can include endocrine therapy, radiotherapy, chemotherapy, bisphosphonates, and/or targeted therapy; which is used depends on the characteristics of the disease [e.g., hormone receptor status, disease site(s), and response to previous treatment] and the patient (age, comorbidity, and personal preferences). For most patients with hormone-receptor-positive tumors, the first choice of treatment is further endocrine therapy, but endocrine resistance is a common problem in advanced disease. Several novel anticancer agents have been developed with the aim of overcoming endocrine resistance, many of which target intracellular signaling pathways implicated in disease progression or resistance. Among these, inhibitors of growth factor receptor tyrosine kinases and of mammalian target of rapamycin have shown the most promise in clinical trials. Chemotherapy is the cornerstone of MBC treatment in most women. Important considerations when choosing chemotherapy include the choice of agents, and whether to use single-agent or combination therapy. Anthracyclines are one of the most active cytotoxic agents currently used for the treatment of breast cancer, and for many women, further anthracycline therapy at progression or relapse would be the preferred option. However, lifetime exposure to anthracyclines is limited by cumulative cardiotoxicity, which often prevents rechallenge in later lines of therapy. Newer anthracycline formulations have been developed with lower cardiotoxicity than the conventional anthracycline doxorubicin, but these agents still impair cardiac function, and have maximum recommended lifetime doses. Recently, the concomitant use of cardioprotective agents, such as dexrazoxane, has emerged as an effective approach to reducing the cardiotoxic effects of anthracyclines, thus permitting retreatment. Bisphosphonates, which are not associated with the acute toxicities of cytotoxic chemotherapy drugs, are the established standard of care for patients with metastatic bone disease, and have greatly improved outcomes over the last decade. The search is ongoing for novel agents that will, hopefully, bring a cure closer to reality.