Abstract P1-09-06: A prospective longitudinal study of the impact of breast cancer treatment with adjuvant chemotherapy or tamoxifen alone on ovarian reserve
Authors: Goldfarb Shari B , Bedoschi Giuliano , Grunblatt Eli , Goswami Sumanta , Cigler Tessa , Quistorff Jessica , Pacheco Fernanda , Stobezki Robert , Robson Mark , Moy Fred , Hudis Clifford , Patil Sujata , Dickler Maura , Oktay Kutluk 
Published: May 2015

Abstract
Background: Many women with breast cancer (BC) of reproductive age would prefer to preserve their fertility and ovarian function, if possible. However, available information is insufficient to predict the likelihood and extent of ovarian damage that will be suffered by an individual woman. In prior studies, menses was used as a surrogate for fertility, but it is a poor marker of future fertility. Preliminary work suggests that anti-mullerian hormone (AMH) may be a better surrogate for ovarian reserve. The goal of this study is to delineate the extent of ovarian damage from specific treatment regimens by using serum AMH. Here we report results from the largest longitudinal study with a pretreatment evaluation to measure the impact of both chemotherapy (chemo) and tamoxifen (tam) on ovarian reserve in BC patients. Methods: A multi-institutional longitudinal IRB-approved study was performed in 207 premenopausal women with stage 0-III BC. AMH levels were evaluated at baseline and 1 yr post completion of adjuvant chemo or 1 yr post initiation of tam. After the exclusions (failure to follow-up, sample inadequacy, presumed PCOS and consent withdrawal), 115 women ages 26-46 (median 38) were available for analysis at 1 yr post treatment (primary endpoint). AMH levels were measured in frozen sera with an in-house ultrasensitive ELISA assay and were log transformed due to non-normal distribution. Results were analyzed with Wilcoxon rank sum test and repeated measures ANOVA to adjust for age, tam use and stage. Results: In the 115 evaluable women, 98 pts had HR positive BC & 17 had triple negative BC. 77 pts received anthracycline-based (ddAC-T/EC-T) chemo, 26 non-anthracycline-based chemo (TC/CMF/TH) & 12 tam only. In the 103 women who received chemo, compared to baseline (median 0.21 ng/ml, 0.001-3.9 ng/ml), AMH levels declined significantly (median 0.11 ng/ml, 0.001-4.47 ng/ml; p&lt;0.0001) at 1 yr post chemo. The type of chemo, stage and adjuvant tam use did not significantly impact the results. In the 12 women who received tam only, compared to baseline (median 0.505 ng/ml, 0.010-1.27 ng/ml), AMH levels declined significantly (median 0.155 ng/ml, 0.010-0.91 ng/ml; p=.0049) at 1 yr. Despite a significant decline in ovarian reserve by AMH, 69% (66/95) of pts who received chemo had return of menses by 1 yr post treatment. Conclusion: This longitudinal study shows that BC chemo is detrimental to ovarian reserve. Although a decline in AMH was also seen in pts treated with tam only, this is a small cohort and the results are hypothesis generating. The decline in AMH may be due to ovarian stimulation from tam, which can cause predominance of larger follicles that produce less AMH rather than actual reduction in ovarian reserve. This needs to be studied in a larger cohort. The fact that the majority of pts resumed their menses despite a significant decline in their ovarian reserve by AMH indicates that resumption of menses is not the best measure of ovarian normalcy/fertility. This new info can be used for counseling pts in childbearing ages so they can make better informed decisions on fertility preservation, if desired. Supported by NIH RO1 HD053112, Jodi Spiegel Fisher Cancer Foundation and Susan G. Komen Foundation.
Citation Format: Shari B Goldfarb, Giuliano Bedoschi, Eli Grunblatt, Sumanta Goswami, Tessa Cigler, Jessica Quistorff, Fernanda Pacheco, Robert Stobezki, Mark Robson, Fred Moy, Clifford Hudis, Sujata Patil, Maura Dickler, Kutluk Oktay. A prospective longitudinal study of the impact of breast cancer treatment with adjuvant chemotherapy or tamoxifen alone on ovarian reserve [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-09-06.