Background: Women ≤45 years (yrs) treated with chemotherapy (CT) for EBC have a high risk of developing CIOF. Awareness of CIOF is essential for young women. 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 (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 samples collected in a time sequence were included. Estradiol (E2), Follicle-Stimulating Hormone (FSH) and Anti-Müllerian Hormone (AMH) were centrally assessed. CIOF was defined as FSH >12.4IU/l and E2 <52.2ng/ml and was analysed per timepoint and according to clinical and treatment-related variables. Results: Median age was 40yrs (range 21-45); 57.2% had BMI 18.5-<25, 41.1% ≥25; 32% had luminal, 35.9% HER2+, 32.0% triple-negative BC. Median hormone levels at baseline for pts <30yrs vs 30-40yrs vs ≥40yrs were: FSH 5.2IU/I vs 5.6IU/I vs 6.4IU/I; E2 101ng/l vs 86ng/l vs 88ng/l; AMH 2.14ng/ml vs 1.58ng/ml vs 0.53ng/ml. 85.7% of pts had CIOF at EOT, 62.2% at 6m, 54.0% at 12m, 43.5% at 18m, 38.3% at 24m. Similar results were observed in 47 pts with all timepoint samples available. Older vs younger pts had more frequently CIOF at EOT (≥40yrs 94.6%, 30-40yrs 82.0%, <30yrs 50.0%, p<0.001). CIOF at EOT was not influenced by BMI. CT agents impacted the rate of CIOF (p<0.001; Table 1). Higher rate of CIOF was associated with longer CT duration (12w 58.3%, 16-18w 94.5%, 24w 82.1%; p<0.001) and with dose-dense (ddEC-ddD, weekly PM(Cb), intense-dd (idd) EnPC) vs conventional dosed CT (P/nP-EC q3w, P, Cz) (94.5% vs 78.6%; p<0.001). Conclusions: The majority of young women experienced CIOF after CT for EBC. After 2 yrs 62% of the pts returned to premenopausal hormone levels. Age, CT regimen, duration and density influenced the rate of CIOF and should be taken into account when counseling young women who desire to maintain ovarian function.

C, cyclophosphamide; Cb, carboplatin; Cz, cabazitaxel; D, docetaxel; E, epirubicin; M, doxorubicin; P, paclitaxel; nP, nab-paclitaxel.