Plasma Anti-Mullerian Hormone Concentrations and Risk of Breast Cancer among Premenopausal Women in the Nurses' Health Studies

Background: Anti-Mullerian hormone (AMH) is a member of the TGF beta family of growth and differentiation factors with a key role in regulating folliculogenesis. In experimental studies, using supraphysiologic concentrations, AMH inhibits breast cancer growth. However, high levels of AMH were associated with increased breast cancer risk in two prior prospective epidemiologic studies. Methods: We conducted a nested case-control study of premenopausal plasma AMH and breast cancer risk within the Nurses' Health Study (NHS) and NHSII. In NHS, 32,826 women donated blood samples in 1989-1990; in NHSII, 29,611 women donated samples in 1996-1999. After blood collection and before February 2004 (NHS) or July 2010 (NHSII), 539 cases were diagnosed among women premenopausal at diagnosis, and were matched 1: 1 to controls. ORs and 95% confidence intervals (CI) were calculated using unconditional logistic regression, adjusting for matching and breast cancer risk factors. Results: Higher plasma levels of AMH were associated with increased breast cancer risk (top vs. bottom quintile multivariate OR, 2.20; 95% CI, 1.34-3.63; P trend = 0.001). The association did not vary by invasive versus in situ disease or by estrogen receptor status. Associations were not significantly different by age at blood or diagnosis. Further adjustment for plasma estradiol or testosterone yielded similar results. Conclusions: Higher circulating AMH levels are associated with increased breast cancer risk among premenopausal women. Impact: The significant positive association between premenopausal plasma AMH levels and subsequent breast cancer risk before menopause suggests AMH may be useful as a marker of breast cancer risk in younger women. (C) 2016 AACR.