Incidence of and Predictive Factors for Recovery of Ovarian Function on Letrozole in ER-Positive Breast Cancer Patients in Their Forties Who Cease Menstruating with Adjuvant Chemotherapy.

Background: We conducted an open-label pilot study of 2 years of aromatase inhibitor (AI) therapy in women in their 409s with ER-positive breast cancer who had ceased menstruating with adjuvant cyclophosphamide-based chemotherapy, had postmenopausal serum estradiol (E2) levels, and had been on tamoxifen (Tam) for at least 1 year. The primary objective was to determine if serial FSH levels while on letrozole predicted for ovarian recovery (resumption of menses or premenopausal E2/FSH levels) and secondary objectives included evaluation of serial E2, inhibin A and B levels and osteopenia on baseline DEXA scan as predictors of ovarian failure. Patients and Methods: Patients who had ceased menstruating and who had a postmenopausal estradiol level on tamoxifen at study entry were treated for up to 2 years with letrozole following at least 1 year of Tam; patients who were on another AI at study entry were permitted to continue on that therapy. All patients underwent evaluation of serum FSH and E2 levels every 3 months for 1 year and then every 6 months during Year 2; baseline and end of Year 1 inhibin A and B levels; and baseline assessment of bone mineral density (BMD). Patients consented to strict birth control measures and stopped letrozole therapy at evidence of ovarian function recovery. Results: 173 patients were enrolled on study and we report now on the findings in the 30 patients 31 pg/mL) without menses; and an additional 6 patients (20%) had isolated premenopausal E2 levels. The average time to recovery of ovarian function as above on letrozole was 14 months (range 2.4 - 29 months). Postmenopausal baseline inhibin A and B levels did not accurately predict for lack of ovarian recovery. Of the 18 patients with menses or biochemical evidence of ovarian recovery, 5 (28%) had osteopenia (T score Conclusion: Women Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 6097.