The association between reproductive and hormonal factors and ovarian cancer by estrogen-α and progesterone receptor status

Objective. We assessed the association between reproductive and hormonal factors and ovarian cancer incidence characterized by estrogen receptor-alpha (ER alpha) and progesterone receptor (PR) status. Methods. Tissue microarrays were used to assess ERa and PR expression among 197 Nurses' Health Study (NHS), 42 NHSII and 76 New England Case-Control Study (NECC) ovarian cancer cases. NHS/NHSII cases were matched to up to 4 controls (n = 954) on diagnosis date and birth year. NECC controls (n = 725) were frequency matched on age. Cases were considered receptor positive if of tumor cells stained positive. Associations by ER alpha and PR status were assessed using polytomous logistic regression. p-Value for heterogeneity was calculated using a likelihood ratio test. Results. 45% of ovarian tumors were PR( +), 78% were ERa (+) and 45% were ER alpha(+)/PR(+), while 22% were ER alpha(-)/PR(-). Postmenopausal status was associated with an increased risk of PR(-) tumors (OR: 2.07; 95%CI: 1.15-3.75; p-heterogeneity = 0.01) and age at natural menopause was inversely associated with PR(-) tumors (OR, per 5 years: 0.77; 95%CI: 0.61-0.96; p-het = 0.01). Increasing duration of postmenopause was differentially associated by PR status (p-het = 0.0009). Number of children and tubal ligation were more strongly associated with ERa(-) versus ER alpha (+) tumors (p-het = 0.002 and 0.05, respectively). No differential associations were observed for oral contraceptive or hormone therapy use. Conclusions. Postmenopausal women have an increased risk of developing PR(-) ovarian tumors compared to premenopausal women. The associations observed for ovarian cancer differ from those seen for breast cancer suggesting that the biology for tumor development through ERa and PR pathways may differ. (C) 2016 Elsevier Inc. All rights reserved.