A shift in the treatment of hormone receptor and human epidermal growth factor receptor 2-positive metastatic breast cancer

摘要

Historically, postmenopausal women with estrogen receptor (ER)-positive metastatic breast cancer (MBC) with a long disease-free interval and small volume disease have received an aromatase inhibitor. However, the advent of human epidermal growth factor receptor 2 (HER2) testing and its recognition as a poor prognostic indicator has led to the first line use of anti-HER2 directed therapy in combination with chemotherapy. The optimal treatment for those who are both hormone receptor and HER2 receptor positive is less clear. Tumors rich in ER are considered to be less responsive to chemotherapy, and hormone therapy has the benefit of being less toxic than chemotherapy. However, preclinical evidence suggests that HER2 overexpression may confer resistance to endocrine therapy, even in the presence of hormone receptors, due to crosstalk between the two pathways. This review summarizes the evidence from three clinical trials for combining endocrine therapy with anti-HER2 therapy in MBC. The trials raise the possibility of a new treatment approach to co-positive tumors in patients with good performance status and low tumor burden, and a means to potentially delay the need for chemotherapy.