Age-associated biomarker profiles of human breast cancer.
To explore the hypothesis that aging not only increases breast cancer incidence but also alters breast cancer biology, we correlated patient age and diagnosis with tumor histology, stage and biomarkers independently determined from two different tumor archives: an American collection of approximately 800 paraffin-embedded and immunohistochemically analyzed primary breast cancers, and an European collection of approximately 3000 cryobanked primary breast cancers analyzed by ligand-binding and enzyme immunoassay (EIA). The prognostic biomarkers chosen for comparison represented surrogate measures of tumor: (i). proliferation, growth and genetic instability (mitotic and apoptotic indices, Ki-67/MIB-1-positivity, nuclear grade, p53-positivity), (ii). endocrine-dependence (estrogen receptor (ER), progesterone receptors (PR), pS2, Bcl2), (iii). growth factor receptor-dependence (ErbB2, EGFR/ErbB1), and (iv). angiogenic, invasive and proteolytic potential (uPA, PAI-1, Cathepsin D, VEGF). No biomarker reflecting tumor angiogenic, invasive or proteolytic potential showed a significant correlation with patient age at diagnosis. In contrast, significant inverse correlations (|r|>0.1; P< or =0.05) were observed for all measures of tumor growth and genetic instability as well as growth factor receptor overexpression (ErbB2 or EGFR positivity). Only one marker of endocrine-dependence, ER expression, showed a significant positive correlation with patient age at diagnosis. In summary, these findings support the hypothesis that breast cancer biology is significantly affected by patient age. In particular, breast tumors arising in older patients have slower growth rates, are more likely to be ER-positive, and are less likely to be p53-positive, EGFR-positive or ErbB2-positive.
Stiftung Tumorbank Basel and Department of Research, University Clinics, Basel, Switzerland.
Serenella
S
Eppenberger-Castori
Dan H
DH
Moore
Ann D
AD
Thor
Susan M
SM
Edgerton
Willy
W
Kueng
Urs
U
Eppenberger
Christopher C
CC
Benz
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D000569:Americas; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000737:chemistry* / Q000175:diagnosis / Q000473:pathology; D002402:Cathepsin D / Q000032:analysis; D003627:Data Interpretation, Statistical; D016228:Endothelial Growth Factors / Q000032:analysis; D066246:ErbB Receptors / Q000032:analysis; D005060:Europe; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000032:analysis; D019394:Ki-67 Antigen / Q000032:analysis; D008222:Lymphokines / Q000032:analysis; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000032:analysis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D011960:Receptors, Estrogen / Q000032:analysis; D016159:Tumor Suppressor Protein p53 / Q000032:analysis; D014568:Urokinase-Type Plasminogen Activator / Q000032:analysis; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D014408:Biomarkers, Tumor; D002402:Cathepsin D; D016228:Endothelial Growth Factors; D066246:ErbB Receptors; D036341:Intercellular Signaling Peptides and Proteins; D019394:Ki-67 Antigen; D008222:Lymphokines; D017395:Plasminogen Activator Inhibitor 1; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D016159:Tumor Suppressor Protein p53; D014568:Urokinase-Type Plasminogen Activator; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors