Abstract P3-12-05: Reduction of ovarian reserve in young early breast cancer patients: 24 months follow up of a prospective cohort trial
Authors: Mundhenke Christoph , Wenners Antonia S , Grambach Jana , Koss Juliane , von Hehn Ulrike , Jonat Walter , Schmutzler Andreas G 
Published: May 2015

Abstract
Background: Sideeffects of adjuvant chemotherapy on ovarian function are inadequately studied by now. Premenopausal women undergoing chemotherapy are at risk for sexual hormone deficiency and impaired fertility. This prospective cohort study searches for predictive parameters of ovarian reserve after chemotherapy. Methods: 51 premenopausal patients (average 38 years; 28-46 years) with primary breast cancer have been included. They all received neo- or adjuvant chemotherapy: anthracycline based "A"(FEC)(n= 18); anthracycline/taxane based "T"( TAC or FEC/Doc or EC/Pac)(n=30) or anthracycline- free "AF"(n=3). After chemotherapy patients received endocrine therapy (ET) for hormone receptor (HR) positive disease (tamoxifen (n=34) or goserelin/tamoxifen (n=7)). For HR negative disease (n=20) no ET was given. Before (visit 1) and 6, 12 and 24 months after initiation of chemotherapy (visit 2-4) age and chemotherapy related changes in hormone (LH, FSH, E2 and Anti-Muellerian hormone (AMH)) levels, antral follicle count and amenorrhea as parameters of endocrine function and fertility were assessed. Also quality of life (QL) and additional impact of parity, BMI and nicotine use on ovarian reserve were evaluated. Results: Antral follicle count is decreasing dramatically after chemotherapy and is not fully recovering after 2 years. Antral follicle count before and 1 year after chemotherapy are significantly correlated (p=0.012). Follicle count and age before chemotherapy are negatively correlated (p=0.004). At visit 4 the type of chemotherapy (A, T, AF) has no influence on antral follicle count or AMH levels. Tamoxifen is correlated with a significant decrease in follicle count (vs. no endocrine therapy) (p=0.039). Smoking is significantly detrimental on antral follicle count after 24 months (p=0.001). AMH levels at visits 2-4 are significantly correlated with levels at the 1 visit and are negatively correlated with age (p=0.032). Tamoxifen therapy has no impact on AMH levels. LH and FSH are increasing between visit 1 and 2 and decreasing at visits 3 and 4 (but stay above basic levels). At visit 4 LH is not and FSH is correlated with visit 1 levels (p=0.005). LH and FSH are correlated with age (p=0.0001) and are not influenced by type of chemotherapy or tamoxifen .E2 levels at visit 4 are not influenced by type of chemotherapy, but significantly decreased (p=0.003) by continued smoking. At visit 4 31/51 patients have stayed amenorrheic, 19 resumed their menstruation. This was not influenced by type of chemotherapy or age. Non- smokers are 13 times more likely to resume their menstruation (vs. smokers). Tamoxifen is correlated with a higher probability of permanent amenorrhea (p=0.058, n.s.). BMI, nicotine abuse, age, type of chemotherapy and tamoxifen have no influence on duration of amenorrhea. QL is significantly lower at visit 2, but recovers to basic values at visits 3 and 4. Conclusions: Our study contributes to a better prediction of ovarian reserve before chemotherapy. We suggest personalized counselling on fertility preserving measures before chemotherapy especially at higher age, with low AMH levels or low antral follicle counts. To stop smoking could enhance chances for ovarian preservation.
Citation Format: Christoph Mundhenke, Antonia S Wenners, Jana Grambach, Juliane Koss, Ulrike von Hehn, Walter Jonat, Andreas G Schmutzler. Reduction of ovarian reserve in young early breast cancer patients: 24 months follow up of a prospective cohort trial [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 P3-12-05.