Adjuvant endocrine therapy for premenopausal women: Type and duration

Abstract

The Early Breast Cancer Trialists' Collaborative Group (EBCTCG) meta-analysis of randomized tamoxifen trials, found that women age <45 years with estrogen receptor-positive (ER+ve) breast cancer, allocated 5 years of adjuvant tamoxifen, have substantial long-term reduction of breast cancer recurrence. Breast cancer mortality was reduced by about one-third through the first 15 years. Increasing the duration of tamoxifen to 10 years can further reduce the risk of recurrence. For women age <45 years allocated 5 years of tamoxifen, the risk of contralateral breast cancer is halved over 15 years.The initial results from the Suppression of Ovarian Function Trial (SOFT) indicate tamoxifen is a suitable therapy for premenopausal women with low risk clinical-pathologic features. For women at sufficient risk to receive chemotherapy who have premenopausal E2 levels within 8 months of completion, the addition of ovarian suppression to tamoxifen for 5 years resulted in some reduction of recurrence. The use of ovarian suppression combined with an aromatase inhibitor exemestane for 5 years, resulted in further reduction of recurrence.The joint analysis of SOFT and Tamoxifen and Exemestane Trial (TEXT) found the combination of ovarian suppression plus exemestane significantly reduced recurrence, compared with ovarian suppression plus tamoxifen. Premenopausal women with ER+ve HER2-negative breast cancer with high-risk features can derive a meaningful improvement in 5-year invasive breast cancer-free interval with exemestane plus ovarian suppression, as an alternative to tamoxifen. Very young women under age 35 with ER+ve breast cancer have higher risks of recurrence, and the use of ovarian suppression with oral endocrine therapy should be considered.