Abstract PD7-09: Changes in hormone levels (E2, FSH, AMH) and fertility of young women treated with neoadjuvant chemotherapy (CT) for early breast cancer (EBC)
Authors: J Furlanetto, C Thode, J Huober, C Denkert, M Bassy, C Hanusch, C Jackisch, S Kümmel, A Schneeweiss, M Untch, PA Fasching, T Karn, F Marmé, M van Mackelenbergh, V Müller, C Schem, G von Minckwitz, D Strik, V Nekljudova, S Loibl
Journal: Cancer Research (2018)

Abstract Background: We previously demonstrated that the majority of women ≤45 years experienced chemotherapy-induced ovarian failure (CIOF) after CT for EBC. Age, CT regimen, duration and dose-density influenced the rate of CIOF. The regain of premenopausal Follicle-Stimulating Hormone (FSH) and Estradiol (E2) levels after chemotherapy is not equivalent to fertility restoration. The Anti-Muellerian Hormone (AMH) assessment seems to be more accurate than other hormones in predicting the ovarian reserve. FSH, E2 and AMH have been prospectively assessed in young patients receiving (neo)adjuvant CT. Methods: 740 patients (pts) aged ≤45yrs treated with anthracycline or taxane-based CT for EBC from 4 German neoadjuvant/adjuvant trials were included. Blood samples were collected at baseline before CT (N=740), end of treatment (EOT n=740), 6 (n=177), 12 (n=113), 18 (n=69), 24 (n=47) months (m) after EOT. Only the full set of samples of a given patient was included. FSH, E2 and AMH were centrally assessed. Postmenopausal hormone levels of FSH and E2 according to the central laboratory were defined as FSH&amp;gt;12.4IU/l and E2&amp;lt;52.2ng/l; fertile level of AMH as ≥0.22ng/ml. Regain of premenopausal hormone levels was defined as the time point from EOT to premenopausal FSH and E2 level regain and was assessed only for those pts with postmenopausal FSH and E2 levels at EOT. Pts with no regain have been censored at the date of the last hormone assessment. Results: Median age was 40yrs (range 21-45); 57.2% had BMI 18.5-&amp;lt;25, 41.1% ≥25; 32% had luminal-like, 35.9% HER2+, 32.0% triple-negative BC. Median hormone levels at different time points are presented in Table 1. Before chemotherapy 14.2% of pts had non-fertile hormone levels of AMH despite premenopausal levels of FSH and E2 compared to 77.3% of pts with postmenopausal levels (p&amp;lt;0.001); at EOT 77.4% vs 99.8% (p&amp;lt;0.001); at 6m 82.1% vs 100% (p&amp;lt;0.001); at 12m 80.7% vs 98.4% (p=0.002); at 18m 66.7% vs 100% (p&amp;lt;0.001); at 24 m 72.4% vs 100% (p=0.017). Similar results were observed in 47 pts with all time point samples available. Of 147 pts with postmenopausal hormone levels of FSH and E2 at EOT, 32.7% (95%CI 25.7%-40.9%) regained premenopausal hormone levels within 6m, 51.0% (95%CI 42.3%-60.4%) within 12m, 66.6% (95%CI 55.2%-77.6%) within 18m and 69.9% (95%CI 57.8%-81.3%) within 24m. Conclusion: Nearly 70% of women regain premenopausal hormone levels of FSH and E2 within 2 years after end of CT. Despite that, only less than one third maintain their fertility potential as predicted by AMH. AMH is a very sensitive marker for the prediction of fertility function after CT for EBC. Table 1 Median and range of FSH, E2 and AMH levels per time pointsTimepointFSH,IU/lE2, ng/mLAMH, ng/ml% of pts with AMH levels above dtBaseline6.0 [dt-142.7]88.0 [dt-2375.0]0.96 [dt-16.18]95.4EOT76.1 [1.9-225.0]dt [dt-632.0]dt [dt -3.11]15.66 m41.4 [1.1-190.6]10.0 [dt-929.0]dt [dt -3.11]26.112 m28.7 [1.1-146.0]11.0 [dt-947.0]dt [dt -2.81]29.218 m20.6 [0.8-172.3]19.0 [dt-624.0]dt [dt -1.89]34.824 m16.30 [dt-93.9]44.0 [dt-11795.0]dt [dt -1.75]38.3Abbreviations: dt, detectable threshold, EOT, end of treatment; m, month; pts, patients. Detectable threshold: FSH&amp;lt;0.1IU/l, E2&amp;lt;5ng/l, AMH&amp;lt;0.03ng/ml Citation Format: Furlanetto J, Thode C, Huober J, Denkert C, Bassy M, Hanusch C, Jackisch C, Kümmel S, Schneeweiss A, Untch M, Fasching PA, Karn T, Marmé F, van Mackelenbergh M, Müller V, Schem C, von Minckwitz G, Strik D, Nekljudova V, Loibl S. Changes in hormone levels (E2, FSH, AMH) and fertility of young women treated with neoadjuvant chemotherapy (CT) for early breast cancer (EBC) [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr PD7-09.