Relationship between Epidemiologic Risk Factors and Hormone Receptor Expression in Ovarian Cancer: Results from the Nurses' Health Study

Abstract

Hormone receptor expression in tumors may offer etiologic information for ovarian cancer, particularly in light of known associations with hormonal and reproductive risk factors. Tissue microarrays constructed from 157 paraffin-embedded blocks of epithelial ovarian tumors collected from participants in the Nurses' Health Study were stained for estrogen receptor-alpha (ERalpha) and progesterone receptor (PR). We examined receptor expression by invasion, grade, and histologic subtype. Multivariate unconditional logistic regression was used to evaluate whether hormonal, reproductive, and anthropometric risk factors were differentially associated with the risk of developing receptor-positive or receptor-negative ovarian tumors compared with controls. PR-expressing tumors were less likely to be invasive (P = 0.05) and more likely to be of a lower grade (P < 0.001) and stage (P = 0.007) compared with PR- tumors. ERalpha status was not associated with any pathologic features of the tumor (P > 0.34). Increasing age, being postmenopausal, and postmenopausal hormone use were associated with an increased risk of developing ERalpha+, but not ERalpha- (P(heterogeneity) = 0.001, 0.06, and 0.06, respectively) and PR-, but not PR+, tumors (P(heterogeneity) = 0.08, 0.003, and 0.40, respectively), whereas height was only associated with the risk of developing PR- disease (P(heterogeneity) = 0.08). There were no clear risk differentials with OC use, parity, body mass index, or physical activity. Reproductive and hormonal risk factors are associated with subgroups of ovarian cancer defined by histologic subtype or ERalpha and PR status. These finding support specific models of hormone mediated triggers of ovarian cancer.