Optimizing Breast Cancer Management

Lisa E. Flaum, William J. Gradishar

A majority of breast cancers are hormone receptor (HR) positive and are responsive to various types of hormone manipulation. Endocrine therapy is the preferred first-line therapy for patients with advanced estrogen receptor (ER) positive, HER2-negative breast cancer who do not have symptomatic visceral disease. Endocrine therapy is often continued in the second- and third-line setting, with chemotherapy deferred until tumor becomes endocrine therapy refractory and/or a visceral crisis in imminent. Therapeutic options vary based on clinical presentation and include single-agent therapies such as tamoxifen, aromatase inhibitors and fulvestrant, and combination therapies options. Over the past few years, multiple trials have shown significant improvement in outcomes when endocrine therapy is combined with CDK 4/6 inhibitors or mTOR inhibitors. Improved efficacy comes at a cost of a modest increase in toxicity. Mechanisms of ER resistance have been defined leading to multiple strategies to improve efficacy and overcome resistance. These include the combination therapies options mentioned above and other novel drugs that are in development. This review will summarize the existing literature regarding endocrine therapy in postmenopausal metastatic breast cancer and outline treatment approaches in the first-line metastatic setting and beyond.