Prediction of postchemotherapy ovarian function using markers of ovarian reserve

Abstract

Background: Reproductive-aged women frequently receive both chemotherapy and endocrine therapy as part of their treatment regimen for early stage hormone receptor-positive breast cancer. Chemotherapy results in transient or permanent ovarian failure in the majority of women. The difficulty in determining which patients will recover ovarian function has implications for adjuvant endocrine therapy decision making. We hypothesized that pretreatment serum anti-Müllerian hormone (AMH) and inhibin B concentrations would predict for ovarian function following chemotherapy.

Methods: Pre- and perimenopausal women aged 25-50 years with newly diagnosed breast cancer were enrolled. Subjects underwent phlebotomy for assessment of serum AMH, inhibin B, follicle-stimulating hormone, and estradiol prior to chemotherapy and 1 month and 1 year following completion of treatment. Associations among hormone concentrations, clinical factors, and biochemically assessed ovarian function were assessed.

Results: Twenty-seven subjects were evaluable for the primary endpoint. Median age was 41. Twenty subjects (74.1%) experienced recovery of ovarian function within 18 months. Of the 26 evaluable subjects assessed prior to chemotherapy, 19 (73.1%) had detectable serum concentrations of AMH. The positive predictive value of a detectable baseline serum AMH concentration for recovery of ovarian function was 94.7%, and the negative predictive value was 85.7%. On univariate analysis, younger age and detectable serum AMH concentration at chemotherapy initiation were predictive of increased likelihood of recovery of ovarian function.

Conclusion: Prechemotherapy assessment of serum AMH may be useful for predicting postchemotherapy ovarian function. This finding has implications for decision making about adjuvant endocrine therapy in premenopausal women treated with chemotherapy.

Trial registration: ClinicalTrials.gov NCT00644683.

Keywords: Anti-Müllerian hormone; Breast cancer; Chemotherapy; Ovarian function.

Conflict of interest statement

Disclosures of potential conflicts of interest may be found at the end of this article.

Figures

Figure 1.

Change in serum concentrations of ovarian reserve markers with chemotherapy. Each line signifies an individual subject. Solid lines: subjects aged >40 years. Dotted lines: subjects aged ≤40 years. Blue lines: subjects with ovarian failure. Red lines: subjects with ovarian function recovery. Black bars: mean hormone concentration at each time point. (A): AMH. (B): Inhibin B. (C): FSH. (D): Estradiol. Abbreviations: AMH, anti-Müllerian hormone; chemo, chemotherapy; FSH, follicle-stimulating hormone.