Optimal Endocrine Therapy in Premenopausal Women: A Pragmatic Approach to Unanswered Questions

Recent epidemiologic data show an increasing incidence of breast cancer among premenopausal women in many higher-income countries. Among premenopausal women, those diagnosed under age 40 years experience inferior long-term outcomes, particularly in the setting of hormone receptor-positive, human epidermal growth factor receptor 2-negative disease. In addition to more advanced disease presentation and/or less favorable disease biology, suboptimal adjuvant endocrine therapy (ET) has emerged as an important driver of this age-related disparity. Historically, young women have been excluded from treatment with aromatase inhibitors (AIs), attained low rates of chemotherapy-related amenorrhea, and exhibited low adherence to ET. Recently, several studies have demonstrated treatment with ovarian function suppression (OFS) during the first 5 years postdiagnosis to be associated with improvements in breast cancer recurrence and mortality, with additional benefits achieved from pairing OFS with an AI. As the first 5 years of ET for premenopausal women has been transformed, extended ET, administered in years 5-10 postdiagnosis, has also become more common. However, the only studies of extending ET in premenopausal women have tested an additional 5 years of tamoxifen following an initial 5 years of tamoxifen and studies of AIs in the second 5 years have been limited to postmenopausal women. Herein, we review available data concerning potential benefits and risks to be considered when counseling premenopausal women on extended ET, including the continuation of OFS. We offer a pragmatic framework to support decision making given the current body of knowledge and call out the need for additional research into this issue.