Abstract P6-05-02: PRESENCE OF BRCA MUTATIONS AND PRE-CHEMOTHERAPY SERUM ANTI-MULLERIAN HORMONE LEVELS PREDICT RISK OF AMENORRHEA IN WOMEN WITH BREAST CANCER
Authors: Goldfarb Shari B. , Turan Volkan , Bedoschi Giuliano , Abdo Nadia , Chang Cassandra , Bang heejung , OKTAY KUTLUK H. 
Published: March 2023

OBJECTIVE: The likelihood of post-chemotherapy (ChT) amenorrhea is still empirically determined. Our aim was to determine the predictors of amenorrhea risk post- ChT in women with breast cancer(ca). As acute amenorrhea (&lt; 12mo post-ChT) can be temporary, we used amenorrhea status 12 and 18 months post-ChT as the primary endpoint.

MATERIALS AND METHODS: 102 women aged 18-44, with regular cycles and stage I-III breast ca were prospectively and longitudinally followed for their menstrual pattern changes at 6, 12, and 18mo after the completion of adjuvant ChT with an Anthracycline-Cyclophosphamide-based (AC) or Cyclophosphamide-Methotrexate +5-Fluorouracil regimen on an IRB-approved protocol. Prior ChT, ovarian surgery, pelvic RT, family history of POI, and infertility diagnosis were the exclusion criteria. AMH was measured pre- and immediately post- ChT. Amenorrhea was defined as no bleeding for 4 consecutive cycles. Preand/or post-ChT AMH levels, age and BMI at the onset of ChT, BMI, tamoxifen use, regimen type (AC-based vs. not), and BRCA mutation (m) status (positive vs. not) were evaluated for the prediction of amenorrhea risk.

RESULTS: In multivariable-adjusted logistic regression models, age (p=0.03) and AMH (p=0.03) were significant predictors of amenorrhea at 12mo, and BRCAm status (p=0.03) at 18 mo; these models yielded areas under the ROC curve of 0.77 and 0.76, respectively. An undetectable AMH post-ChT was best predictive of amenorrhea with shorter follow-up, but not at 18mo. In longitudinal analysis (with data at 0, 6, 12, and 18 months) estimating ‘time-trends’, a baseline AMH &lt; 2.0 ng/ml (optimal cut-off from ROC curve) and BRCAm status were associated with the risk of amenorrhea. The baseline AMH ≥2.0 group showed attenuated time-trend vs. the AMH &lt; 2.0 ng/ml group (ratio of ORs=0.91, 95% CI=0.86-0.97, p=0.002), while the BRCA-positive group showed a steeper time-trend in the odds ratio (OR) of amenorrhea, compared to the non-positive group (ratio of ORs=1.12,95% CI=1.04-1.20, p=0.003) (Table 1). Sensitivity analyses demonstrated the robustness of these findings, for example, yielding an 8-10% increased risk of amenorrhea for BRCAm carriers, with p-values of 0.008- 0.04.

CONCLUSIONS: Age, pre-and post-ChT AMH levels, and BRCAm status are potential predictors of amenorrhea at 12 and 18mo post-ChT. These predictors may help better guide fertility preservation decision-making in women with breast ca. The higher likelihood of amenorrhea in women with BRCAm suggests that they may be more prone to lose their ovarian function post-ChT and should be accordingly counseled.

Table 1. Longitudinal analysis at 0, 6, 12 and 18 months for the difference in amenorrhea trend between groups dichotomized by baseline factors.

Citation Format: Shari B. Goldfarb, Volkan Turan, Giuliano Bedoschi, Nadia Abdo, Cassandra Chang, heejung Bang, KUTLUK H. OKTAY. PRESENCE OF BRCA MUTATIONS AND PRE-CHEMOTHERAPY SERUM ANTI-MULLERIAN HORMONE LEVELS PREDICT RISK OF AMENORRHEA IN WOMEN WITH BREAST CANCER [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-05-02.