Abstract B41: Serum MIS and breast cancer risk Free

B41

Mullerian inhibiting substance (MIS) is a member of the transforming growth factor β family of growth and differentiation factors known primarily for its role in regulating in-utero sexual differentiation of males. In the female breast, MIS inhibits elongation and branching of mammary ducts. In vitro and in animal models, MIS inhibits growth of mammary tumors. Thus, we hypothesized that MIS may be a novel biomarker of decreased breast cancer risk. The objective of this study was to prospectively determine if MIS levels in serum are related to breast cancer risk. A case-control study was performed nested in the Columbia, Missouri Serum Bank. Each of 129 cases with prediagnostic serum collected before menopause were matched to 2 controls on age, date, menstrual cycle day, and time of day of blood collection. MIS was measured in serum by ELISA. Data analysis was performed using conditional logistic regression. Contrary to expectations, results of preliminary analysis indicate that premenopausal women with elevated serum MIS levels are at an increased risk of breast cancer. Median MIS concentrations in cases and controls were .3 ng/ml and .1 ng/ml, respectively (p=.002). Women in the highest MIS quartile had a RR = 6.6 (95% CI = 2.5 - 17.4; trend-p <.0001). Tests for interaction with OC use were significant. In analysis restricted to women not taking OC’s (117 matched sets) the comparable RR=4.3 (95% CI = 1.5 - 12.1; trend-p=.006). Adjustment for serum estradiol and testosterone concentrations did not materially alter results. MIS could increase breast cancer risk via direct effects on the breast or correlation with other ovarian hormones associated with risk. MIS declines with ovarian aging and women with higher MIS levels may have a later age of menopause contributing to their increased breast cancer risk. Further research on the association of MIS with breast cancer is clearly needed.

Citation Information: Cancer Prev Res 2008;1(7 Suppl):B41.