Expression of hormone receptor and HER2 identify different breast cancer subtypes with distinct biology, clinical behavior, and treatment sensitivity. Hormone receptor positive (HR+) tumors are largely dependent on hormones, and endocrine manipulation is the cornerstone of therapy. In the case of concomitant HER2 overexpression, HER2 blockade is critical to allow for endocrine responsiveness.
Several strategies to block or interfere with hormones are available, including ovarian function suppression (pre-menopause), selective estrogen receptor modulators (SERMs), aromatase inhibitors, and estrogen receptor down-regulators. The more efficacious endocrine agents are progressively incorporated into the adjuvant treatment; therefore, the optimal strategy for patients who eventually relapse is largely influenced by their prior exposure to adjuvant therapies.
Patients with HR+/HER2 negative disease might benefit from sequential use of all available endocrine agents, delaying the use of chemotherapy. The combination of endocrine therapy plus anti-HER2 agents is a valid option for selected patients with HR+/HER2+ disease not immediately requiring chemotherapy. New strategies to overcome endocrine resistance, such as co-targeting the mTOR pathway, are promising.