Comparison of breast cancer risk factors among molecular subtypes: A case-only study

Epidemiological studies have a clear definition of the risk factors for breast cancer. However, it is unknown whether the distribution of these factors differs among breast cancer subtypes. We conducted a hospital-based case-only study consisting of 8067 breast cancer patients basing on the Tianjin Cohort of Breast Cancer Cases. Major breast cancer subtypes including luminal A, luminal B, human epidermal growth factor receptor 2 (HER2)-enriched and basal-like were defined by estrogen receptor, progesterone receptor, HER2, and Ki-67 status. Variables including demographic characteristics, reproductive factors, lifestyle habits, imaging examination, and clinicopathologic data were collected for patients. Chi-square test and one-way analysis of variance were used to compare the distributions of variables among the four breast cancer subtypes. Multivariate logistic regression was used to estimate the odds ratios and associated 95% confidence intervals where luminal A patients served as the reference group. Overall, more commonality rather than heterogeneity on the distributions of factors was found between the four molecular subtypes of breast cancer. The proportion of overweight and obesity were lower in HER2-enriched subtype. Women with age at menarche ≤13 years were more likely to be found in basal-like subtype. Postmenopausal women were more frequent in HER2-enriched and basal-like subtypes. Women with benign breast disease and higher breast density were more common in HER2-enriched subtype. Risk factor scoring showed that total risk scores were similar among the four subtypes. HER2-enriched and basal-like subtypes were more frequently diagnosed with large tumors. Calcification was more likely to be found in luminal B and HER2-enriched subtypes, whereas less distributed in basal-like subtype. Most of the breast cancer risk factors were similarly distributed among the four major breast cancer subtypes; commonality is predominant.