The Impact of Reproductive Factors on the Risk of Breast Cancer by ER/PR and HER2: A Multicenter Case-Control Study in Northern and Eastern China

BACKGROUND: Previous studies have suggested that reproductive factors are associated with breast cancer risk. Breast cancer subtypes have distinct natural characteristics and may also have unique risk profiles. The purpose of this study was to determine whether reproductive factors affect the risk of breast cancer by estrogen receptor (ER)/progesterone receptor (PR) and HER2 status. METHODS: A multicenter, case-control study was conducted. There were 1170 breast cancer patients and 1170 age- and hospital-matched females included in the analysis. Self-reported data were collected about lifestyle behaviors, including reproductive factors. Breast cancer cases were categorized subtypes according to ER, PR, and HER2 expression as HR- positive, HER2-enriched, and triple negative breast cancer (TNBC). Multivariable logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Having ≤1 child increased risk of HR-positive breast cancer (OR 1.882; 95%CI 1.29-2.74), especially in the premenopausal group (OR 2.212; 95%CI 1.23-3.99). Compared with women who first gave birth after age 30 years, earlier age at first birth decreased the risk of HR-positive breast cancer (≤23 years: OR 0.209; 95%CI 0.14-0.30; 24-29 years: OR 0.256; 95%CI 0.18-0.36; P < .001). Compared with those who had an average breastfed/birth period of more than 2 years, those with an average period less than 6 months had an elevated risk of all subtypes (HR positive: OR 2.690; 95%CI 1.71-4.16, P < .001; HER2-enriched: OR 3.779; 95%CI, 1.62-8.79, P = .001; TNBC: OR 2.564; 95%CI 1.11-5.94, P = .022). For postmenopausal patients, shorter period of lifetime menstrual cycles (≤30 years) had an obviously decreased risk in HR-positive cases (OR 0.397; 95%CI 0.22-0.71), while there was no similar appearance in other molecular subtypes. CONCLUSION: The results suggest that reproductive behaviors affect risk of breast cancer differently according to ER/PR and HER2 status.