Etiology of hormone receptor-defined breast cancer: A systematic review of the literature

Michelle D. Althuis, Jennifer H. Fergenbaum, Montserrat Garcia-Closas, Louise A. Brinton, M. Patricia Madigan, Mark E. Sherman

Research output: Contribution to journalReview articlepeer-review

476 Scopus citations


Breast cancers classified by estrogen receptor (ER) and/ or progesterone receptor (PR) expression have different clinical, pathologic, and molecular features. We examined existing evidence from the epidemiologic literature as to whether breast cancers stratified by hormone receptor status are also etiologically distinct diseases. Despite limited statistical power and nonstandardized receptor assays, in aggregate, the critically evaluated studies (n = 31) suggest that the etiology of hormone receptor-defined breast cancers may be heterogeneous. Reproduction-related exposures tended to be associated with increased risk of ER-positive but not ER-negative tumors. Nulliparity and delayed childbearing were more consistently associated with increased cancer risk for ER-positive than ER-negative tumors, and early menarche was more consistently associated with ER-positive/PR-positive than ER-negative/PR- negative tumors. Postmenopausal obesity was also more consistently associated with increased risk of hormone receptor-positive than hormone receptor-negative tumors, possibly reflecting increased estrogen synthesis in adipose stores and greater bioavailability. Published data are insufficient to suggest that exogenous estrogen use (oral contraceptives or hormone replacement therapy) increase risk of hormone-sensitive tumors. Risks associated with breast-feeding, alcohol consumption, cigarette smoking, family history of breast cancer, or premenopausal obesity did not differ by receptor status. Large population-based studies of determinants of hormone receptor-defined breast cancers defined using state-of-the-art quantitative immunostaining methods are needed to clarify the role of ER/PR expression in breast cancer etiology.

Original languageEnglish (US)
Pages (from-to)1558-1568
Number of pages11
JournalCancer Epidemiology Biomarkers and Prevention
Issue number10
StatePublished - Oct 1 2004

ASJC Scopus subject areas

  • Epidemiology
  • Oncology


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