Traditional breast cancer risk factors in relation

Authors: Rulla M Tamimi Graham A Colditz Aditi Hazra Heather J Baer Susan E Hankinson Bernard Rosner Jonathan Marotti James L Connolly Stuart J Schnitt Laura C Collins

Publish Date: 2011/08/10

Volume: 131, Issue: 1, Pages: 159-167

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Abstract

At least four major categories of invasive breast cancer have been reproducibly identified by gene expression profiling luminal A luminal B HER2type and basallike These subtypes have been shown to differ in their outcome and response to treatment Whether this heterogeneity reflects the evolution of these subtypes through distinct etiologic pathways has not been clearly defined We evaluated the association between traditional breast cancer risk factors and risk of previously defined molecular subtypes of breast cancer in the Nurses’ Health Study This analysis included 2022 invasive breast cancer cases for whom we were able to obtain archived breast cancer tissue specimens Tissue microarrays TMAs were constructed and slides were immunostained for estrogen receptor ER progesterone receptor PR human epidermal growth factor receptor 2 HER2 cytokeratin 5/6 CK5/6 and epidermal growth factor receptor EGFR Using immunostain results in combination with histologic grade cases were grouped into molecularly defined subtypes We used Cox proportional hazards models to estimate hazard ratios HRs and 95 confidence intervals CIs We observed differences in the association between risk factors and subtypes of breast cancer In general many reproductive factors were most strongly associated with the luminal A subtype although these differences were not statistically significant Weight gain since age 18 showed significant differences in its association with molecular subtypes Pheterogeneity = 005 and was most strongly associated with the luminal B subtype Ptrend 0001 Although there was not significant heterogeneity for lactation across subtypes an inverse association was strongest for basallike tumors HR = 06 95 CI 04–08 Pheterogeneity = 088 These results support the hypothesis that different subtypes of breast cancer have different etiologies and should not be considered as a single group Identifying risk factors for less common subtypes such as luminal B HER2type and basallike tumors has important implications for prevention of these more aggressive subtypesWe thank the participants and staff of the Nurses’ Health Study cohort for their valuable contributions We thank the following state cancer registries for their help AL AZ AR CA CO CT DE FL GA ID IL IN IA KY LA ME MD MA MI NE NH NJ NY NC ND OH OK OR PA RI SC TN TX VA WA and WY The study sponsors had no role in the design of the study the collection analysis and interpretation of the data the writing of the manuscript or the decision to submit the manuscript for publicationSupported by GlaxoSmithKline WE234 EPI40307 Public Health Service Grants CA087969 and SPORE in Breast Cancer CA089393 from the National Cancer Institute National Institutes of Health Department of Health and Human Services and Breast Cancer Research Fund Dr Graham Colditz is supported in part by an American Cancer Society Cissy Hornung Clinical Research Professorship

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