Human epidermal growth factor receptor-2 and hormonal therapies: clinical implications.

Estrogen-targeted therapies such as administration of tamoxifen or aromatase inhibitors are among the most important treatment strategies in the modern management of breast cancer. Despite initial responses in the metastatic setting and prolonged disease-free intervals in the adjuvant setting, many patients subsequently become resistant to these agents. Human epidermal growth factor receptor-2 (HER2) is a transmembrane glycoprotein receptor that is overexpressed in 13%-30% of human breast cancers. There are experimental data suggesting an important role for HER2 in de novo and acquired resistance to endocrine therapies. These experimental data are discussed in this article, as are clinical data addressing the role of HER2 in resistance to endocrine therapy in the adjuvant, neoadjuvant, and metastatic settings. Responses and benefit from tamoxifen appear to be impaired in patients in whom HER2 is overexpressed. In contrast, early data from the neoadjuvant setting suggest that responses to aromatase inhibitors may be maintained in patients with HER2 overexpression.