Incidence and predictors of ovarian function recovery (OFR) in breast cancer (BC) patients with chemotherapy-induced amenorrhea (CIA) who switched from tamoxifen to exemestane

Background: Aromatase inhibitors (AIs) may promote ovarian function recovery (OFR). True incidence, predictors and impact on the outcome of OFR are unknown. Patients and methods: We carried out a prospective study to assess ovarian function in estrogen receptor (ER)-positive BC patients on tamoxifen who had at least 2 years of chemotherapy-induced amenorrhea (CIA) and postmenopausal E2 levels. Patients switched to exemestane and underwent a series of investigations including vaginal ultrasound, antimullerian hormone, follicle stimulating hormone (FSH), and E2. E2 measurements were made using a clinical assay (direct) and a highly sensitive (indirect) immunoassay for comparison. Results: Both E2 assays (indirect versus direct) showed a similar incidence of OFR 32% (95% CI 19.5-44.5) versus 30% (95% CI 17.7-42.3) and median time to OFR 5.4 months (95% CI 1.2-9.6) versus 6.0 months (95% CI 4.8-7.1). On multivariate analysis, the mean age at the start of exemestane treatment was the only marker associated with probability of OFR (OR: 0.44, 0.24-0.78; P = 0.006). According to a receiver operating characteristic (ROC) analysis, age <48 years predicted for OFR (sensitivity: 59%; 1-specificity: 17%; AUC: 0.796; P=0.001). Patients with OFR had higher mean E2 levels (43.6 versus 5.76 pmol/l; P=0.001) and a reduced disease-free survival IDES; HR 9.3 (95% Cl 3.3-48.0; P = 0.04)] than those without it. Conclusion: Even with a clinical and biochemical profile compatible with menopause, switching from tamoxifen to an AI should be avoided in patients <48 with CIA.