Department of Obstetrics and Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut, USA.
Department of Obstetrics and Gynecology, Istanbul Health and Technology University School of Medicine, Istanbul, Turkey.
Cancer Med. 2023 Sep;12(18):19225-19233. doi: 10.1002/cam4.6527. Epub 2023 Sep 12.
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.
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.
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 <18 month follow-up. In longitudinal analysis estimating time trends, baseline AMH and gBRCApv status was associated with the risk of amenorrhea over 6-18 months; the AMH >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).
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.
为了进行生育力保留决策，需要更好的工具来评估化疗后闭经风险。我们的目的是确定乳腺癌患者化疗后 12 个月和 18 个月闭经风险的预测因素。
142 名乳腺癌患者在接受蒽环类药物环磷酰胺（AC 方案）或环磷酰胺甲氨蝶呤+5-氟尿嘧啶方案辅助化疗后 6、12 和 18 个月进行了纵向随访，以了解月经变化。评估化疗前和/或化疗后 AMH 水平、年龄、BMI、他莫昔芬使用、方案类型和种系 BRCA 致病性变异（gBRCApv）状态，以预测 6-18 个月时的闭经。
在多变量调整的逻辑回归中，12 个月时年龄（p=0.03）和 AMH（p=0.03），以及 18 个月时 gBRCApv 状态（p=0.03）是 102 名可评估患者闭经的显著预测因素（12 个月和 18 个月时 ROC 曲线下面积分别为 0.77 和 0.76）。化疗后即刻 AMH 不可检测可预测 18 个月内闭经。在估计时间趋势的纵向分析中，基线 AMH 和 gBRCApv 状态与 6-18 个月闭经风险相关；AMH>2.0ng/mL 组闭经时间趋势风险较 AMH≤2.0ng/mL 组降低（OR 比值 0.91，95%CI 0.86-0.97，p=0.002），而 gBRCApv+组与对照组相比，时间趋势风险更高（OR 比值 1.12，95%CI 1.04-1.20，p=0.003）。
除了治疗前后的 AMH 水平外，gBRCApv 状态是化疗后 12 个月和 18 个月闭经的潜在新预测因素。gBRCApv 阳性女性闭经的可能性更高，这表明她们在化疗后更有可能失去生育能力。
