Variation in breast cancer hormone receptor and HER2 levels by etiologic factors: A population-based analysis

Mark E. Sherman, David L. Rimm, Xiaohong R. Yang, Nilanjan Chatterjee, Louise A. Brinton, Jolanta Lissowska, Beata Peplonska, Neonila Szeszenia-Da̧browska, Witold Zatonski, Richard Cartun, Daniza Mandich, Grzegorz Rymkiewicz, Marcin Ligaj, Stanisław Lukaszek, Radzislaw Kordek, Zynep Kalaylioglu, Malini Harigopal, Lori Charrette, Roni T. Falk, Douglas RichessonWilliam F. Anderson, Stephen M. Hewitt, Montserrat García-Closas

Research output: Contribution to journalArticle

42 Scopus citations

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-α and PR status of tumors based on clinical records according to etiologic exposure data collected via interview. For 842 cancers, we evaluated ER-α, ER-β, PR and HER2 levels by semiquantitative microscopic scoring of immunostained tissue microarrays and a quantitative immunofluorescence method, automated quantitative analysis (AQUA™). 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.

Original languageEnglish (US)
Pages (from-to)1079-1085
Number of pages7
JournalInternational Journal of Cancer
Volume121
Issue number5
DOIs
StatePublished - Sep 1 2007

Keywords

  • Breast
  • Epidemiology
  • Etiology
  • Hormones

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Sherman, M. E., Rimm, D. L., Yang, X. R., Chatterjee, N., Brinton, L. A., Lissowska, J., Peplonska, B., Szeszenia-Da̧browska, N., Zatonski, W., Cartun, R., Mandich, D., Rymkiewicz, G., Ligaj, M., Lukaszek, S., Kordek, R., Kalaylioglu, Z., Harigopal, M., Charrette, L., Falk, R. T., ... García-Closas, M. (2007). Variation in breast cancer hormone receptor and HER2 levels by etiologic factors: A population-based analysis. International Journal of Cancer, 121(5), 1079-1085. https://doi.org/10.1002/ijc.22812