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McCarthy AM, Friebel-Klingner T, Ehsan S, et al. Relationship of established risk factors with breast cancer subtypes. Cancer Med. 2021;10(18):6456-6467doi: 10.1002/cam4.4158.
McCarthy, A. M., Friebel-Klingner, T., Ehsan, S., He, W., Welch, M., Chen, J., Kontos, D., Domchek, S. M., Conant, E. F., Semine, A., Hughes, K., Bardia, A., Lehman, C., & Armstrong, K. (2021). Relationship of established risk factors with breast cancer subtypes. Cancer medicine, 10(18), 6456-6467. https://doi.org/10.1002/cam4.4158
McCarthy, Anne Marie, et al. "Relationship of established risk factors with breast cancer subtypes." Cancer medicine vol. 10,18 (2021): 6456-6467. doi: https://doi.org/10.1002/cam4.4158
McCarthy AM, Friebel-Klingner T, Ehsan S, He W, Welch M, Chen J, Kontos D, Domchek SM, Conant EF, Semine A, Hughes K, Bardia A, Lehman C, Armstrong K. Relationship of established risk factors with breast cancer subtypes. Cancer Med. 2021 Sep;10(18):6456-6467. doi: 10.1002/cam4.4158. Epub 2021 Aug 31. PMID: 34464510; PMCID: PMC8446564.
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Cancer Med. 2021 Sep;10(18):6456-6467. doi: 10.1002/cam4.4158. Epub 2021 Aug 31.

Relationship of established risk factors with breast cancer subtypes.

Cancer medicine

Anne Marie McCarthy, Tara Friebel-Klingner, Sarah Ehsan, Wei He, Michaela Welch, Jinbo Chen, Despina Kontos, Susan M Domchek, Emily F Conant, Alan Semine, Kevin Hughes, Aditya Bardia, Constance Lehman, Katrina Armstrong

Affiliations

  1. University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
  2. Massachusetts General Hospital, Boston, Massachusetts, USA.
  3. Draper Laboratory, Boston, Massachusetts, USA.
  4. Newton Wellesley Hospital, Newton, Massachusetts, USA.
  5. Harvard Medical School, Boston, Massachusetts, USA.

PMID: 34464510 PMCID: PMC8446564 DOI: 10.1002/cam4.4158

Abstract

BACKGROUND: Breast cancer is a heterogeneous disease, divided into subtypes based on the expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). Subtypes have different biology and prognosis, with accumulating evidence of different risk factors. The purpose of this study was to compare breast cancer risk factors across tumor subtypes in a large, diverse mammography population.

METHODS: Women aged 40-84 without a history of breast cancer with a screening mammogram at three United States health systems from 2006 to 2015 were included. Risk factor questionnaires were completed at mammogram visit, supplemented by electronic health records. Invasive tumor subtype was defined by immunohistochemistry as ER/PR+HER2-, ER/PR+HER2+, ER, and PR-HER2+, or triple-negative breast cancer (TNBC). Cox proportional hazards models were run for each subtype. Associations of race, reproductive history, prior breast problems, family history, breast density, and body mass index (BMI) were assessed. The association of tumor subtypes with screen detection and interval cancer was assessed using logistic regression among invasive cases.

RESULTS: The study population included 198,278 women with a median of 6.5 years of follow-up (IQR 4.2-9.0 years). There were 4002 invasive cancers, including 3077 (77%) ER/PR+HER2-, 300 (8%) TNBC, 342 (9%) ER/PR+HER2+, and 126 (3%) ER/PR-HER2+ subtype. In multivariate models, Black women had 2.7 times higher risk of TNBC than white women (HR = 2.67, 95% CI 1.99-3.58). Breast density was associated with increased risk of all subtypes. BMI was more strongly associated with ER/PR+HER2- and HER2+ subtypes among postmenopausal women than premenopausal women. Breast density was more strongly associated with ER/PR+HER2- and TNBC among premenopausal than postmenopausal women. TNBC was more likely to be interval cancer than other subtypes.

CONCLUSIONS: These results have implications for risk assessment and understanding of the etiology of breast cancer subtypes. More research is needed to determine what factors explain the higher risk of TNBC for Black women.

© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Keywords: breast cancer; cancer epidemiology; etiology; risk factors; tumor subtypes

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