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Hormonal Markers in Breast Cancer: Coexpression, Relationship with Pathologic Characteristics, and Risk Factor Associations in a Population-Based Study

¹ Division of Cancer Epidemiology & Genetics, ² Tissue Array Research Program, Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, NIH, Department of Health and Human Services, Bethesda, Maryland; ³ Department of Pathology, Yale University School of Medicine, New Haven, Connecticut; ⁴ Department of Cancer Epidemiology and Prevention, Cancer Center and M. Sklodowska-Curie Institute of Oncology, Warsaw, Poland; ⁵ Department of Occupational and Environmental Epidemiology, Nofer Institute of Occupational Medicine, ód, Poland; ⁶ Department of Pathology, Hartford Hospital, Hartford, Connecticut; ⁷ Department of Pathology, Tohoku University School of Medicine, Sendai, Japan; ⁸ Novartis Institutes for BioMedical Research Basel, Oncology Research, Basel, Switzerland; and ⁹ W. Harry Feinstone Center for Genomic Research, University of Memphis, Memphis, Tennessee

Requests for reprints: Xiaohong Rose Yang, Genetic Epidemiology Branch, Division of Cancer Epidemiology & Genetics, National Cancer Institute, 6120 Executive Boulevard, Room 7014, Bethesda, MD 20892-7236. Phone: 301-594-7804; Fax: 301-402-4489; E-mail: royang{at}mail.nih.gov.

The objective of this study was to evaluate the coexpression patterns of hormonal markers in breast cancer tissue and their relationship with pathologic characteristics and epidemiologic risk factors. We evaluated the expression of 17 markers by immunohistochemistry in 842 invasive breast carcinomas collected in a population-based case-control study conducted in Poland. Based on marker correlations, factor analysis identified four major coexpression patterns (factors): "nuclear receptor factor" [estrogen receptor (ER)-, progesterone receptor, androgen receptor, cyclin D1, and aromatase], "estrogen metabolism/ER-ß factor" (ER-ß, peroxisome proliferator-activated receptor-, steroid sulfatase, estrogen sulfonotransferase, and cytochrome P450 1B1), "HER2 factor" (human epidermal growth factor receptor 2, E-cadherin, cyclooxygenase-2, aromatase, steroid sulfatase), and "proliferation factor" (cytokeratin 5, cytokeratin 5/6, epidermal growth factor receptor, P53). Three of these factors corresponded to molecular subtypes previously defined by expression profiling; however, the estrogen metabolism/ER-ß factor seemed to be distinctive. High scores for this factor were associated with high tumor grade (P heterogeneity = 0.02), younger age at menarche (P heterogeneity = 0.04), lower current body mass index among premenopausal women (P heterogeneity = 0.01), and older age at menopause (P heterogeneity = 0.04). High scores for the proliferation factor were also associated with early menarche (P heterogeneity < 0.0001), and in contrast to the estrogen metabolism/ER-ß factor, higher current body mass index among premenopausal women (P heterogeneity = 0.03). Our analysis of hormonal pathway markers independently confirmed several previously defined molecular subtypes identified by gene expression profiling and augmented these findings by suggesting the existence of additional relationships related to ER-ß and enzymes involved in hormone metabolism. [Cancer Res 2007;67(21):10608–17]

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