Background: Although the clinical relevance of molecular subtypes of breast cancer has been examined, little is known about risk factors for different tumor subtypes, especially the HER2-overexpressing and triple-negative subtypes. Previous epidemiologic findings imply these subtypes may also vary with respect to risk factor profiles; however, these results were based mainly on older or younger cases in western countries. Our objective was to determine the different risk factors by breast cancer subtypes in Korean.

Methods: In this study, cases were diagnosed with breast cancer and underwent curative surgery at two teaching hospitals located in Seoul, Korea, between 2000 and 2007. Control subjects were selected from two sources: records of the hospital based case-control study and community based health examination in the same duration. Total 2,473 cases and matched controls were eligible to analysis further study. Information was collected using a standardized questionnaire and breast tumours were tested by immunohistochemistry. Odds ratios (OR) and 95% confidence intervals (CI) of risk of molecular subtypes of breast cancer were calculated using a multivariate polytomous regression model, adjusting age at diagnosis.

Results: In our study, 1,590 (65.6%) tumors were considered luminal (ER+ and/or PR+), 327 (13.5%) HER-2 overexpressing (ER-, PR-, HER-2+), and 505 (20.9%) triple negative (ER-, PR-, and HER-2-). We observed statistically strong significant differences in means or frequencies by tumor subtypes for age at diagnosis, education level, menopausal status, a family history of breast cancer and tumor size (p<0.0001). In a multivariate model, relative risks differed by molecular subtypes, comparing controls, for age at diagnosis, education level. In pre-menopausal women, higher body mass index (BMI) was associated with increased risk of triple negative tumors (OR=1.6, 95% CI 1.1-2.3), whereas higher BMI was inversely associated with risk of HER-2 overexpressing (3 tertile vs. 1st tertile: OR=0.6, 95% CI 0.3-0.9). In post-menopausal women, reduced risk associated with triple negative tumours (3rd tertile vs. 1st tertile: OR=0.5, 95% CI 0.3-0.8) was examined. And compared to luminal tumors, late age at menarche was significantly strongly associated with HER2-overexpressing (>=15 vs. <15: OR=2.1, 95% CI 1.4-3.2). On the other hand, reduced risk associated with higher age at diagnosis was stronger for triple-negative (> 50 vs. < 40: OR=0.5, 95% CI 0.3-0.8, p-trend <.0001) which was consistent with previous results.

Conclusion: Our findings suggest that risk profiles may be different by molecular subtypes, especially body mass index in stratified analysis by menopausal status. However, underlying mechanisms need to be investigated in further study.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5704.