Impact of Anti-HER2 Therapy Alone and with Weekly Paclitaxel on the Ovarian Reserve of Young Women with HER2-Positive Breast Cancer

Background: The potential gonadotoxicity of anti-HER2 agents remains largely unknown, and limited, conflicting evidence exists for taxanes. Antimullerian € hormone (AMH) is an established biomarker of ovarian reserve that may aid in quantifying anticancer treatment–induced gonadotoxicity. Patients and Methods: The present biomarker analysis of the randomized phase III neoadjuvant NeoALTTO trial included premenopausal women aged #45 years at diagnosis of HER2-positive early breast cancer with available frozen serum samples at baseline (ie, before anticancer treatments), at week 2 (ie, the “biological window” of antiHER2 therapy alone), and/or at the time of surgery (ie, after completing paclitaxel 1 anti-HER2 therapy, before starting adjuvant chemotherapy). Results: The present analysis included 130 patients with a median age of 38 years (interquartile ratio [IQR], age 33–42 years). AMH values at the 3 time points differed significantly (P,.001). At baseline, median AMH levels were 1.29 ng/mL (IQR, 0.56–2.62 ng/mL). At week 2, a small but significant reduction in AMH levels was observed (median, 1.10 ng/mL; IQR, 0.45–2.09 ng/mL; P,.001). At surgery, a larger significant decline in AMH levels was observed (median, 0.01 ng/mL; IQR, 0.01–0.03 ng/mL; P,.001). Although the type of anti-HER2 treatment (trastuzumab and/or lapatinib) did not seem to impact the results, age and pretreatment ovarian reserve had a major influence on treatment-induced gonadotoxicity risk. Conclusions: This NeoALTTO biomarker analysis showed that anti-HER2 therapies alone had limited gonadotoxicity but that the addition of weekly paclitaxel resulted in marked AMH decline with possible negative implications for subsequent ovarian function and fertility.