Targeted Therapy for Premenopausal Women with HR+, HER2- Advanced Breast Cancer: Focus on Special Considerations and Latest Advances

The incidence of advanced breast cancer in premenopausal women is increasing, and breast cancer in younger women is often more aggressive and has a worse prognosis compared with breast cancer in older women. Premenopausal women with hormone receptor-positive (HR+) breast cancer are frequently under-represented in clinical trials, and treatment strategies in the premenopausal setting are usually extrapolated from data from postmenopausal patients, with the addition of ovarian function suppression to endocrine therapy in HR+ disease. However, the underlying biology of breast cancer in premenopausal women can be different from postmenopausal women, and treatment strategies should ideally be specifically tested in premenopausal patients. Recent phase III trials have now investigated cyclin-dependent kinase 4/6 (CDK4/6) inhibitors in premenopausal patients with HR+, HER2(+) advanced breast cancer: Palbociclib and abemaciclib have been tested in a subset of premenopausal patients in the PALOMA-3 andMONARCH-2studies, and ribociclib has been tested in the phase III MONALEESA-7 trial, which was entirely dedicated to premenopausal women. This comprehensive review summarizes the differences in the biology of HR+, HER2(+) breast cancer in the premenopausal population compared with the postmenopausal population; discusses special considerations for treatment of premenopausal women; and reviews the evidence from clinical trials investigating endocrine therapy, other targeted treatments, and ovarian function suppression in the HR thorn, HER2(+) advanced breast cancer setting. (C) 2018 AACR.