Metastatic breast cancer: therapeutic options according to molecular subtypes and prior adjuvant therapy

In spite of advances in treatment strategies, about 25%-40% of patients with breast cancer still eventually develop metastatic disease that is largely incurable. Treatment goals vary from symptom control to lengthening survival, mainly on the basis of patient age and performance status, tumor biology, site and extent of disease, and prior therapies. In particular, breast cancer molecular characterization allows for the identification of breast cancer subtypes with distinct biological features, a distinct clinical course, and distinct treatment sensitivity. Endocrine manipulation is the cornerstone of therapy in hormone receptor-positive tumors; anti-human epidermal growth factor receptor (HER)-2 agents are essential in the management of HER-2(+) tumors; and chemotherapy is the only available option so far for the triple-negative subtype. In each of these subtypes, the more efficacious agents have been progressively incorporated into adjuvant treatment. As a consequence, the choice of the optimal therapeutic strategy for patients with metastatic disease is largely influenced by prior exposure to adjuvant therapies. This review contextualizes the data from clinical trials into different clinical scenarios of metastatic disease, taking into account the molecular subtype and prior adjuvant treatments.