Abstract
Background: We conducted an open-label pilot study of 2 years of aromatase inhibitor (AI) therapy in women in their 40's 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 <45 years old (mean age 43). 96% of the patients were on letrozole. Median time from end of cyclophosphamide to start of letrozole was 23 months and median duration of Tam treatment prior to starting letrozole was 18 months. Seven patients (23%) resumed menses; 5 additional patients (17%) developed both premenopausal levels of FSH (<23 IU/L) and E2 (>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 <-1) at study entry while 4 of 12 patients (33%) without ovarian recovery had baseline osteopenia. In patients who had ovarian recovery on letrozole, FSH levels that were suppressed on Tam tended to rise over 6-10 months on letrozole and then return to premenopausal levels.Conclusion: Women <45 years of age who have persistent amenorrhea with adjuvant chemotherapy followed by Tam have a high incidence of ovarian recovery on letrozole. After initial rises in FSH levels following the switch from Tam to letrozole, subsequent declines in FSH levels predict for ovarian recovery.Supported, in part, by Novartis Pharmaceuticals, Corp., East Hanover, NJ.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 6097.
Volume 69, Issue 24 Supplement
