A prospective longitudinal analysis of the predictors of amenorrhea after breast cancer chemotherapy: Impact of BRCA pathogenic variants

Abstract

Abstract Background Better tools for post‐chemotherapy amenorrhea risk assessment are needed for fertility preservation decision‐making. Our aim was to determine the predictors of amenorrhea risk at 12 and 18 months post‐chemotherapy in women with breast cancer. Methods 142 women with breast cancer were longitudinally followed for their menstrual changes at 6, 12, and 18 months after the completion of adjuvant chemotherapy with an Anthracycline‐Cyclophosphamide‐based (AC‐based) or Cyclophosphamide‐Methotrexate +5‐Fluorouracil regimen. Pre‐ and/or post‐chemo AMH levels, age, BMI, tamoxifen use, regimen type, and germline BRCA pathogenic variant (gBRCApv) status were evaluated for the prediction of amenorrhea at 6–18 months. Results In multivariable‐adjusted logistic regression, age (p = 0.03) and AMH (p = 0.03) at 12 months, and gBRCApv status (p = 0.03) at 18 months were significant predictors of amenorrhea (areas under the ROC curve of 0.77 and 0.76, for 12 and 18 months, respectively) among 102 evaluable subjects. An undetectable AMH immediately post‐chemotherapy was predictive of amenorrhea with 2.0 ng/mL group showed attenuated time‐trend risk of amenorrhea versus AMH ≤2.0 group (ratio of ORs = 0.91, 95% CI = 0.86–0.97, p = 0.002), while the gBRCApv + showed a steeper time trend, versus the controls (ratio of ORs = 1.12, 95% CI = 1.04–1.20, p = 0.003). Conclusions In addition to the pre‐ and post‐treatment AMH levels, gBRCApv status is a novel potential predictor of amenorrhea at 12 and 18 months after chemotherapy. The higher likelihood of amenorrhea in women gBRCApv suggests that they are more prone to losing their fertility post‐chemotherapy.

Keywords

• amenorrhea
• anti‐mullerian hormone
• BRCA
• breast cancer
• chemotherapy
• fertility preservation