Quantitative measurement of epidermal growth factor receptor is a negative predictive factor for tamoxifen response in hormone receptor positive premenopausal breast cancer.
OBJECTIVE
Although there is evidence for interaction between epidermal growth factor receptor (EGFR) and estrogen receptor (ER), it is still not clear how this affects response to endocrine therapies like tamoxifen. Here we assess the relationship between EGFR expression and tamoxifen response, with a new quantitative technology.


METHODS
A tissue microarray was constructed from breast cancer from a cohort of 564 patients enrolled in a randomized clinical trial for adjuvant tamoxifen treatment in early breast cancer, with a median follow-up of 14 years. EGFR expression was measured using automated quantitative analysis, a fluorescence-based method for quantitative analysis of in situ protein expression.


RESULTS
In ER-positive patients, tamoxifen-treated patients with low EGFR expression (n = 113) showed a significant effect by 2 years of adjuvant tamoxifen (P = .01), in contrast to no treatment effect in the EGFR-high group (n = 73, P = .69). The untreated group showed 49% v 57% 10-year recurrence-free survival for EGFR low versus high (P = .466) in the corresponding group of ER-positive patients. A significant beneficial effect of tamoxifen treatment was seen in the EGFR-low group (hazard ratio [HR] = 0.43 (95% CI, 0.22 to 0.84; P = .013) in contrast to no effect in the EGFR-high group (HR = 1.14; 95% CI, 0.59 to 2.22; P = .7) by using a Cox model.


CONCLUSIONS
This study provides clinical evidence that confirms the basic work that has shown high EGFR can indicate resistance to tamoxifen. It suggests that careful measurement of EGFR protein expression might define a subset of low-stage patients that could benefit from an alternative therapy.
Giltnane
Jennifer M
JM
Department of Pathology, Yale University School of Medicine, New Haven, CT 06520-8023, USA.
Rydén
Lisa
L
Cregger
Melissa
M
Bendahl
Pär-Ola
PO
Jirström
Karin
K
Rimm
David L
DL
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000032:analysis; D001707:Biopsy, Needle; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D019008:Drug Resistance, Neoplasm; D066246:ErbB Receptors / Q000032:analysis* / Q000187:drug effects; D004965:Estrogen Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D015999:Multivariate Analysis; D011237:Predictive Value of Tests; D017697:Premenopause; D011336:Probability; D016016:Proportional Hazards Models; D011960:Receptors, Estrogen / Q000378:metabolism*; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D016019:Survival Analysis; D013629:Tamoxifen / Q000009:adverse effects / Q000627:therapeutic use*
D015415:Biomarkers; D004965:Estrogen Antagonists; D011960:Receptors, Estrogen; D013629:Tamoxifen; D066246:ErbB Receptors