PD04-01: Predictors of Recovery of Ovarian Function during Aromatase Inhibitor (AI) Therapy.
Authors: Henry NL , Banerjee M , Hayden J , Yakim E , Schott AF , Stearns V , Partridge AH , Hayes DF 
Published: June 2012

Abstract
Background: AIs may cause a paradoxical rise in estrogen levels due to re-activation of ovarian function in women with chemotherapy-induced ovarian failure (CIOF). Therefore, identification of residual ovarian estradiol production is critical if such women are treated with adjuvant AI therapy rather than tamoxifen. We performed a prospective registry trial to identify predictors of recovery of ovarian function during AI therapy.
Methods: Women with hormone receptor (HR) positive breast cancer who were pre- or peri-menopausal at diagnosis and who remained amenorrheic for ≥8 weeks after cyclophosphamide-containing adjuvant chemotherapy were enrolled in a multi-institutional, open-label clinical trial of anastrozole (1 mg/day). Following confirmation that serum estradiol (E2) levels were &lt;20 pg/ml using an ultrasensitive E2 assay (Quest Diagnostics), subjects initiated anastrozole. Serum E2 was assessed biweekly for 12 wks, then less frequently, for 72 wks. Multivariable logistic regression was used to evaluate clinical predictors (age at AI initiation OR chemotherapy, menopausal status at chemotherapy, body mass index (BMI), baseline E2) of recovery of ovarian function defined as elevated serum E2 levels or return of menses.
Results: Sixty-nine women were enrolled; current status is given in Table 1.

Median age at initiation of chemotherapy was 47.2 yrs (range 37–55), median time since chemotherapy was 0.8 yrs (range 0.3–6.4), and median age at enrollment was 49.8 yrs (range 40–58). Thirty-six had received tamoxifen. We observed elevated E2 concentrations or return of menses during AI therapy in 21 subjects after a median 2.0 mo (range 0.6-17); for that cohort, median age at chemotherapy was 43.8 yrs (range 37–51) and median age at AI initiation was 45.8 yrs (range 40–56). In contrast, for the 15 subjects who had postmenopausal E2 levels for at least 48 wks, median age at chemotherapy was 49.2 yrs (range 44–52) and median age at AI initiation was 50.7 yrs (range 44–55). Age at chemotherapy (p=0.0006) and age at AI initiation (p=0.001) were statistically significant different between the 2 cohorts. On multivariable analysis, age at chemotherapy and age at AI initiation remained significant when each was adjusted for menopausal status, BMI, and baseline E2 (odds ratio (OR) 1.64, p=0.0102 and OR 1.47, p=0.015, respectively).
Conclusions: A significant proportion of women who develop CIOF recover ovarian function during AI therapy. Although recovery is usually rapid, it can occur at least one year following initiation of AI therapy. Younger age was the strongest predictor of recovery of ovarian function, although 2 of 21 women who developed elevated E2 levels or return of menses were older than 50 yrs at the time of chemotherapy. Tamoxifen remains the standard of care for women with CIOF; if use of an AI is necessary, patients should be monitored frequently with high-quality E2 assays for recurrent ovarian function.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr PD04-01.