Variation in breast cancer hormone receptor and HER2 levels by etiologic factors: a population-based analysis.
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.
Sherman
Mark E
ME
Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, DHHS, Bethesda, MD, USA. shermanm@mail.nih.gov
Rimm
David L
DL
Yang
Xiaohong R
XR
Chatterjee
Nilanjan
N
Brinton
Louise A
LA
Lissowska
Jolanta
J
Peplonska
Beata
B
Szeszenia-Dabrowska
Neonila
N
Zatonski
Witold
W
Cartun
Richard
R
Mandich
Daniza
D
Rymkiewicz
Grzegorz
G
Ligaj
Marcin
M
Lukaszek
Stanisław
S
Kordek
Radzislaw
R
Kalaylioglu
Zynep
Z
Harigopal
Malini
M
Charrette
Lori
L
Falk
Roni T
RT
Richesson
Douglas
D
Anderson
William F
WF
Hewitt
Stephen M
SM
García-Closas
Montserrat
M
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
D014408:Biomarkers, Tumor; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D018719:Erb-b2 Receptor Tyrosine Kinases; D011980:Receptors, Progesterone