Perils of Prolonged Ovarian Suppression and Hypoestrogenism in the Treatment of Breast Cancer: Is the Risk of Treatment Worse than the Risk of Recurrence?

Premenopausal breast cancer is usually estrogen receptor positive, and hence, prolonged ovarian suppression by medical or surgical means to prevent recurrence has become standard of management to improve disease-free survival. Ten-year adjuvant tamoxifen therapy is associated with 3.5% fewer recurrences compared to five years. The SOFT trial demonstrated small but statistically significant incremental improvements in long-term disease-free survival by the addition of gonadotropin-releasing hormone analog treatment (triptorelin) to an aromatase inhibitor (exemestane). Profound hypoestrogenism in the premenopausal age group may not be well tolerated due to a host of bothersome side effects (primarily vasomotor symptoms, musculoskeletal complaints, genitourinary syndrome of menopause, and mood disorders). Prolonged hypoestrogenism in younger women is associated with premature development of cardiovascular disease, bone loss, cognitive decline, and all-cause mortality. This paper explores multi-system consequences of prolonged hypoestrogenism in premenopausal women derived from studies of women with and without breast cancer. Pretreatment counseling in estrogen receptor positive breast cancer should emphasize the benefit of prolonged estrogen suppression on breast cancer recurrence and established risks of lifelong hypoestrogenism on quality of life and all-cause mortality. Future genomic research may help identify the best candidates for extended ovarian suppression to avoid treating many women when only a minority benefit.