title: Hormonal markers in breast cancer: coexpression, relationship with pathologic characteristics, and risk factor associations in a population-based study.
abstract: 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)-alpha, progesterone receptor, androgen receptor, cyclin D1, and aromatase], "estrogen metabolism/ER-beta factor" (ER-beta, peroxisome proliferator-activated receptor-gamma, 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-beta 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-beta 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-beta and enzymes involved in hormone metabolism.
authors.affiliation: Genetic Epidemiology Branch, Division of Cancer Epidemiology & Genetics, National Cancer Institute, NIH, Bethesda, MD 20892-7236, USA. royang@mail.nih.gov
authors.forename: Xiaohong R
authors.initials: XR
authors.lastname: Yang
authors.forename: Ruth M
authors.initials: RM
authors.lastname: Pfeiffer
authors.forename: Montserrat
authors.initials: M
authors.lastname: Garcia-Closas
authors.forename: David L
authors.initials: DL
authors.lastname: Rimm
authors.forename: Jolanta
authors.initials: J
authors.lastname: Lissowska
authors.forename: Louise A
authors.initials: LA
authors.lastname: Brinton
authors.forename: Beata
authors.initials: B
authors.lastname: Peplonska
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Hewitt
authors.forename: Richard W
authors.initials: RW
authors.lastname: Cartun
authors.forename: Daniza
authors.initials: D
authors.lastname: Mandich
authors.forename: Hironobu
authors.initials: H
authors.lastname: Sasano
authors.forename: Dean B
authors.initials: DB
authors.lastname: Evans
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Sutter
authors.forename: Mark E
authors.initials: ME
authors.lastname: Sherman
mesh_terms: D000328:Adult; D000368:Aged; D001141:Aromatase / Q000032:analysis; D015992:Body Mass Index; D001943:Breast Neoplasms / Q000737:chemistry* / Q000209:etiology* / Q000473:pathology; D016022:Case-Control Studies; D066246:ErbB Receptors / Q000032:analysis; D047628:Estrogen Receptor alpha / Q000032:analysis; D047629:Estrogen Receptor beta / Q000032:analysis; D004967:Estrogens / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D012307:Risk Factors; D046888:Tissue Array Analysis; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
chemical_list: D001141:Aromatase; D066246:ErbB Receptors; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens; D018719:Erb-b2 Receptor Tyrosine Kinases; D016159:Tumor Suppressor Protein p53