title: Variation in breast cancer hormone receptor and HER2 levels by etiologic factors: a population-based analysis.
abstract: Evidence suggests that breast cancer hormone receptor status varies by etiologic factors, but studies have been inconsistent. In a population-based case-control study in Poland that included 2,386 cases and 2,502 controls, we assessed ER-alpha and PR status of tumors based on clinical records according to etiologic exposure data collected via interview. For 842 cancers, we evaluated ER-alpha, ER-beta, PR and HER2 levels by semiquantitative microscopic scoring of immunostained tissue microarrays and a quantitative immunofluorescence method, automated quantitative analysis (AQUAtrade mark). We related marker levels in tumors to etiologic factors, using standard regression models and novel statistical methods, permitting adjustment for both correlated tumor features and exposures. Results obtained with different assays were generally consistent. Receptor levels varied most significantly with body mass index (BMI), a factor that was inversely related to risk among premenopausal women and directly related to risk among postmenopausal women with larger tumors. After adjustment for correlated markers, exposures and pathologic characteristics, PR and HER2 AQUA levels were inversely related to BMI among premenopausal women (p-trend = 0.01, both comparisons), whereas among postmenopausal women, PR levels were associated directly with BMI (p-trend = 0.002). Among postmenopausal women, analyses demonstrated that BMI was related to an interaction of PR and HER2: odds ratio (OR) = 0.86 (95% CI = 0.69-1.07) for low PR and HER2 expression vs. OR = 1.78 (95% CI = 1.25-2.55) for high expression (p-heterogeneity = 0.001). PR and HER2 levels in breast cancer vary by BMI, suggesting a heterogeneous etiology for tumors related to these markers.
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, DHHS, Bethesda, MD, USA. shermanm@mail.nih.gov
authors.forename: Mark E
authors.initials: ME
authors.lastname: Sherman
authors.forename: David L
authors.initials: DL
authors.lastname: Rimm
authors.forename: Xiaohong R
authors.initials: XR
authors.lastname: Yang
authors.forename: Nilanjan
authors.initials: N
authors.lastname: Chatterjee
authors.forename: Louise A
authors.initials: LA
authors.lastname: Brinton
authors.forename: Jolanta
authors.initials: J
authors.lastname: Lissowska
authors.forename: Beata
authors.initials: B
authors.lastname: Peplonska
authors.forename: Neonila
authors.initials: N
authors.lastname: Szeszenia-Dabrowska
authors.forename: Witold
authors.initials: W
authors.lastname: Zatonski
authors.forename: Richard
authors.initials: R
authors.lastname: Cartun
authors.forename: Daniza
authors.initials: D
authors.lastname: Mandich
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Rymkiewicz
authors.forename: Marcin
authors.initials: M
authors.lastname: Ligaj
authors.forename: Stanisław
authors.initials: S
authors.lastname: Lukaszek
authors.forename: Radzislaw
authors.initials: R
authors.lastname: Kordek
authors.forename: Zynep
authors.initials: Z
authors.lastname: Kalaylioglu
authors.forename: Malini
authors.initials: M
authors.lastname: Harigopal
authors.forename: Lori
authors.initials: L
authors.lastname: Charrette
authors.forename: Roni T
authors.initials: RT
authors.lastname: Falk
authors.forename: Douglas
authors.initials: D
authors.lastname: Richesson
authors.forename: William F
authors.initials: WF
authors.lastname: Anderson
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Hewitt
authors.forename: Montserrat
authors.initials: M
authors.lastname: García-Closas
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor; D015992:Body Mass Index; D001943:Breast Neoplasms / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D047629:Estrogen Receptor beta / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D011159:Population Surveillance; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000378:metabolism*; D012307:Risk Factors
chemical_list: D014408:Biomarkers, Tumor; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D018719:Erb-b2 Receptor Tyrosine Kinases; D011980:Receptors, Progesterone