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Reproductive and hormonal risk factors for postmenopausal luminal, HER2-overexpressing, and triple-negative breast cancer

Phipps, Amanda I. and Malone, Kathleen E. and Porter, Peggy L. and Daling, Janet R. and Li, Christopher I. (2008) Reproductive and hormonal risk factors for postmenopausal luminal, HER2-overexpressing, and triple-negative breast cancer. Cancer. ISSN 1097-0142

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Background: Molecular profiling studies have identified subtypes of breast cancer that can be approximately classified by estrogen receptor (ER), progesterone receptor (PR), and HER2-neu (HER2) expression. These molecular subtypes are prognostically significant, but differences in their etiologic profiles have not been established. Reproductive factors may plausibly be differentially related to risk of different breast cancer subtypes since these factors are presumed to impact exposure to endogenous sex hormones. Methods: We pooled two population-based case-control studies of breast cancer in women aged 55-79 years, for an analysis including 1,476 controls and 1,023 luminal, 39 HER2-overexpressing, and 78 triple-negative cases. Polytomous logistic regression was used to compare each case group to controls. Results: Associations varied by molecular subtype. Early age at menarche was only associated with risk of HER2-overexpressing disease [odds ratio (OR)=2.7, 95% confidence interval (CI): 1.4-5.5], while breastfeeding for 6 months or longer was only protective for luminal and triple-negative disease (OR=0.8, 95% CI:0.6-1.0 and OR=0.5, 95% CI: 0.3-0.9, respectively). Both late age at menopause and use of estrogen plus progestin hormone therapy were only associated with risk of luminal disease (OR=1.6, 95% CI: 1.1-2.2, and OR=1.7, 95% CI: 1.3-2.1, respectively). No differences in risks associated with parity or age at first live birth were observed by subtype. Conclusions: Certain reproductive factors may have a greater impact on risk of certain molecular subtypes of disease compared to others. Future studies that further define the etiology of breast cancer subtypes will add to our biological understanding of the disease.

Item Type: Article or Abstract
Additional Information: The publisher requires that this paper be restricted for internal use only. To access a copy, please use the 'Request a Copy' button above to contact the corresponding author.
DOI: 10.1002/cncr.23786
PubMed ID: 18726992
PMCID: PMC2587413
Grant Numbers: R01 CA072787-05, R01 CA85913-05, 1 TL1 RR025016-01
Keywords or MeSH Headings: Aged Breast Feeding Breast Neoplasms/etiology* Case-Control Studies Female Hormone Replacement Therapy/adverse effects Humans Middle Aged Neoplasms, Hormone-Dependent/etiology Odds Ratio Parity Postmenopause Pregnancy Receptor, erbB-2/metabolism* Reproductive History* Risk Factors
Subjects: Diseases > Solid tumors > Breast cancer
Molecules > Hormones
Research Methodologies > Epidemiology > Risk assessment
Depositing User: authors@FHCRC Administrator-Import
Date Deposited: 27 Aug 2008 23:18
Last Modified: 14 Feb 2012 14:42

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