TY - JOUR
T1 - Variation in breast cancer hormone receptor and HER2 levels by etiologic factors
T2 - A population-based analysis
AU - Sherman, Mark E.
AU - Rimm, David L.
AU - Yang, Xiaohong R.
AU - Chatterjee, Nilanjan
AU - Brinton, Louise A.
AU - Lissowska, Jolanta
AU - Peplonska, Beata
AU - Szeszenia-Da̧browska, Neonila
AU - Zatonski, Witold
AU - Cartun, Richard
AU - Mandich, Daniza
AU - Rymkiewicz, Grzegorz
AU - Ligaj, Marcin
AU - Lukaszek, Stanisław
AU - Kordek, Radzislaw
AU - Kalaylioglu, Zynep
AU - Harigopal, Malini
AU - Charrette, Lori
AU - Falk, Roni T.
AU - Richesson, Douglas
AU - Anderson, William F.
AU - Hewitt, Stephen M.
AU - García-Closas, Montserrat
PY - 2007/9/1
Y1 - 2007/9/1
N2 - 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.
AB - 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.
KW - Breast
KW - Epidemiology
KW - Etiology
KW - Hormones
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U2 - 10.1002/ijc.22812
DO - 10.1002/ijc.22812
M3 - Article
C2 - 17487843
AN - SCOPUS:34547095767
SN - 0020-7136
VL - 121
SP - 1079
EP - 1085
JO - International Journal of Cancer
JF - International Journal of Cancer
IS - 5
ER -