Breast cancer risk factors according to joint estrogen receptor and progesterone receptor status

Background: We investigated risk factor patterns for subtypes of breast cancer characterized by joint estrogen receptor (ER) and progesterone receptor (PR) status in a hospital-based case-control study. Methods: ER and PR tumor status were determined immunohisotchemically. Risk factors of interest were entered into a multiple polychotomous logistic regression model simultaneously; odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Using this model, cases in the four tumor subtypes (ER⁺PR⁺, ER ^-PR^-, ER⁺PR^-, ER^-PR ⁺) were compared simultaneously to controls. A Wald test for heterogeneity across the four subtypes was conducted, as well as a case-case comparison between the two most biologically disparate subtypes, ER ⁺PR⁺ and ER^-PR^-. Results: The receptor status distribution was as follows: 33% ER⁺PR⁺, 34% ER^-PR^-, 20% ER⁺PR^-, and 13% ER^-PR⁺. Among 317 cases and 401 controls, we found significant heterogeneity across the four tumor subtypes for older age at first full-term pregnancy (p = 0.04) and post-menopausal status (p = 0.04). For older age at first full-term pregnancy, an elevated risk was found for the ER ⁺PR^- subtype (OR = 2.5; 95% CI: 1.2-5.1). For post-menopausal status, elevated risks were found for both the ER ⁺PR⁺ (OR = 2.4; 95% CI: 1.1-4.9) and ER⁺PR ^- (OR = 7.2; 95% CI: 2.4-21.7) subtypes. From the case-case comparisons, we found that cases, who had consumed alcohol for more than 1 year were 3.4 times more likely to have ER⁺PR⁺ tumors than ER^-PR^- tumors (95% CI: 1.4-8.4). Conclusions: Certain breast cancer risk factors may vary by ER and PR status, and joint ER/PR status should be taken into account in future studies of risk factor estimates.