Epidermal growth factor receptor expression in breast cancer association with biologic phenotype and clinical outcomes

BACKGROUND: Epidermal growth factor receptor (EGFR) expression is associated with aggressive phenotypes in preclinical breast cancer models, but in clinical studies, EGFR has been inconsistently linked to poor outcome. We hypothesized that EGFR expression in human breast tumors, when centrally and u...

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Published in:Cancer 2010-03, Vol.116 (5), p.1234-1242
Main Authors: Rimawi, Mothaffar F., Shetty, Priya B., Weiss, Heidi L., Schiff, Rachel, Osborne, C. Kent, Chamness, Gary C., Elledge, Richard M.
Format: Article
Language:English
Subjects:
Age Factors
Biological and medical sciences
Breast cancer
Breast Neoplasms - metabolism
Breast Neoplasms - mortality
Breast Neoplasms - pathology
Cancer
chemotherapy resistance
EGFR
ErbB Receptors - metabolism
estrogens
Ethnicity
Female
Frozen Sections
growth factors
Gynecology. Andrology. Obstetrics
Hormones
Humans
Lymphatic Metastasis
Mammary gland diseases
Medical sciences
Middle Aged
Neoplasms, Hormone-Dependent - metabolism
Phenotype
Prognosis
resistance to endocrine therapy
survival
Treatment Outcome
Tumors
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Summary:BACKGROUND: Epidermal growth factor receptor (EGFR) expression is associated with aggressive phenotypes in preclinical breast cancer models, but in clinical studies, EGFR has been inconsistently linked to poor outcome. We hypothesized that EGFR expression in human breast tumors, when centrally and uniformly assessed, is associated with an aggressive phenotype and resistance to systemic therapy. METHODS: In a database of 47,286 patients with breast cancer, EGFR status was known on 2567 tumors. EGFR levels were measured centrally by ligand binding assay, and tumors with ≥10 fmol/mg were prospectively deemed positive. Clinical and biological features of EGFR‐positive and EGFR‐negative tumors were compared. Clinical outcomes were assessed by systemic therapy status. RESULTS: Of 2567 tumors, 475 (18%) were EGFR positive. EGFR‐positive tumors were more common in younger and in black women, were larger, had a higher S‐phase fraction, and were more likely to be aneuploid. EGFR‐positive tumors were more likely to be HER2‐positive (26% vs 16%, P < .0001), but less likely to be estrogen receptor‐positive (60% vs 88%, P < .0001) or progesterone receptor‐positive (26% vs 65%, P < .0001). In multivariate analyses, EGFR expression independently correlated with worse disease‐free survival (hazard ratio [HR] = 1.66; 95% confidence interval [CI], 1.4‐2.41, P = .007) and overall survival (HR = 1.98, 95% CI, 1.36‐2.88, P = .0004) in treated patients, but not in untreated patients. CONCLUSIONS: EGFR expression is more common in breast tumors in younger and black women. It is associated with lower hormone receptor levels, higher proliferation, genomic instability, and HER2 overexpression. It is correlated with higher risk of relapse in patients receiving adjuvant treatment. Blocking EGFR may improve outcome in selected patients. Cancer 2010. © 2010 American Cancer Society. Although epidermal growth factor receptor (EGFR) has a potent impact on breast cancer preclinical models, clinical studies on this biomarker yielded mixed results. This article provides EGFR expression data and its associated clinical and biologic phenotypes on a large set of breast tumors, along with long follow‐up and outcome data.
ISSN:0008-543X
1097-0142
1097-0142
DOI:10.1002/cncr.24816