Hormonal Changes during Extended Letrozole Treatment after Completion of 5 Years of Tamoxifen in Premenopausal Patients with Breast Cancer who Became Postmenopausal

Abstract

Purpose: Extended treatment with aromatase inhibitors (AIs) after tamoxifen has shown effectiveness in postmenopausal patients with breast cancer. However it is very difficult to start on AIs for patients who become postmenopausal after tamoxifen because tamoxifen is a selective estrogen receptor modulator (SERM) that influences menopause, confusing the menopausal status of patients. We assessed the menopausal status and hormone concentrations at the start of letrozole treatment in women with breast cancer who were premenopausal when diagnosed with breast cancer and who became postmenopausal during 5 years of tamoxifen therapy. Methods: We evaluated 164 patients with breast cancer who received extended letrozole therapy between May 2006 and December 2007. All had been premenopausal at diagnosis but became postmenopausal during 5 years of tamoxifen therapy. Menopause was defined as amenorrhea for >1 year, serum follicle stimulating hormone (FSH) concentration ≥30 mIU/mL or serum estradiol (E2) concentrations ≤20 pg/mL. FSH and E2 concentrations were monitored for 2 years after starting letrozole therapy. Results: The median ages of the 164 patients were 45 years at surgery, 46 years when they became amenorrheic, and 50 years at the start of letrozole treatment. Of the 164 patients, 157 (95.7%) were amenorrheic, 14 (9.3%) had FSH concentrations ≥30 mIU/mL and 113 (70.2%) had E2 concentrations ≤20 pg/mL at the start of letrozole. FSH concentrations ≥30 mIU/mL were observed in 87 patients (57.6%) after 6 months of letrozole and in 133 (88.1%) after 2 years, and E2 concentrations ≤20 pg/mL were observed in 164 patients (100%) after 2 years. Times to reach FSH ≥30 mIU/mL and E2 levels ≤20 pg/mL were not significantly related to age at surgery (p=0.836 and p= 0.228, respectively), at start of letrozole (p=0.855 and p= 0.357, respectively), or at amenorrhea (p=0.098 and p= 0.154, respectively). Conclusion: Applying postmenopausal ranges of hormone concentrations observed in normal healthy people to patients who completed 5 years of tamoxifen is inappropriate, because tamoxifen itself may affect FSH concentration. Further studies should focus on identifying an indicator of ovarian function so that these patients can start extended hormone therapy.