Prospective study of the prognostic significance of epidermal growth factor receptor in primary breast cancer

Abstract

Bearing in mind the continuing controversy over the prognostic significance of epidermal growth factor receptor (EGF-r) expression, we investigated its clinical significance prospectively in 345 primary breast cancer patients. The prognostic significance of EGF-r expression, as measured by a radioligand binding assay, was determined by Cox's multivariate analysis using EGF-r concentration as a continuous or dichotomous variable. Increased EGF-r expression was detected in 2632% of tumours, depending on the cut-off in concentration used. EGF-r expression, irrespective of the cut-off, was not associated with tumour size or grade or the number of axillary nodes involved. There was, however, a strong inverse association between EGF-r expression and the absence of hormone receptors. After a median follow-up period of 57 months, multivariate analysis suggested that EGF-r expression was associated with increases in risk for both relapse and death from breast cancer, even after adjusting for oestrogen receptor (ER) concentration, tumour size and the number of axillary nodes involved. Patients with ER-positive tumours, which also expressed EGF-r, had increases in risk for both relapse and death from breast cancer compared with tumours without EGF-r. Expression of EGF-r was not a predictor of poor prognosis in either node-negative or ERnegative subgroups of patients.o 1996 Wiley-Liss, Inc.During the past several years a number of new biological parameters of primary tumours have been studied as potential predictors of prognosis in breast cancer (Osborne, 1992). Although the study of some of these parameters has improved our understanding of the nature of breast cancer progression, controversy continues about their independent prognostic value as most published reports have been based on retrospective studies containing small numbers of patients. Some of the methodological problems associated with recent studies on prognostic factors in breast cancer have been highlighted (Hilsenbeck et al., 1992;Altman et al., 1994). The independent value of epidermal growth factor receptor (EGF-r) in predicting breast cancer prognosis is no exception to the continuing debate (reviewed in Klijn et al., 1992). The lack of standardisation during measurement of EGF-r was identified as one of the most important factors limiting its use as a prognostic indicator. We have addressed this issue and recommended guidelines for handling tumour samples for EGF-r measurement (McLeay et al., 1992). In the present prospective study, we report the prognostic significance of EGF-r expression in primary breast cancer. MATERIAL AND METHODS Clinical profile of the patient populationTumour samples were obtained from 345 women diagnosed with primary breast cancer in South Australia between November 1989 and December 1990. After initial biopsy to confirm diagnosis, 23% and 77% of patients underwent partial mastectomy followed by radiotherapy or total mastectomy alone, respectively. All patients had axillary node clearance to determine the extent of tumour involv...

Epidermal growth factor receptor expression correlates with poor survival in patients who have breast carcinoma treated with doxorubicin‐based neoadjuvant chemotherapy

“…[13][14][15][16][17] In one of those studies, Klijn et al 13 compiled the published data on EGFR expression in 5232 patients with breast carcinoma from 40 series. Overall, 45% of the tumors in their report were EGFR-positive, a rate that is much higher than the 16% noted in the current series.…”

Gene delivery using a receptor-mediated gene transfer system targeted to hepatocellular carcinoma cells

“…40,41 Such over-expression of EGFR is also seen in a wide variety of cancers including breast, 42 colon, 43 ovarian 44 and gliomas. 45 Because the EGFR is accessible on cell surfaces and internalizes after ligand binding, it is a suitable target for tumor-cell-specific therapies that involve intracellular delivery of macromolecules.…”

Structural Basis of EGFR Dimerization for Drug Design

“…Increased expression of the EGF receptor (ErbB) and ErbB2 have been associated with aggressive tumors of the stomach, bladder, lung and breast. 20% of breast cancers are malignant by virtue of their abnormally high expression of EGFR and overexpression correlates with aggressive cancer and poor prognosis (6,16,17). Overexpression of either EGFR or ErbB2 correlates with poor prognosis (6,14,(16)(17)(18).…”

“…20% of breast cancers are malignant by virtue of their abnormally high expression of EGFR and overexpression correlates with aggressive cancer and poor prognosis (6,16,17). Overexpression of either EGFR or ErbB2 correlates with poor prognosis (6,14,(16)(17)(18). Moreover, data from numerous studies suggest that EGFR family members may participate in a complex yet flexible network of signal transduction by forming heterodimers between family members (19-21).…”

“…Heimer et cd. I Journal of Imnumological Methods 248 (2001) [17][18][19][20][21][22][23][24][25][26][27][28][29][30] CHO/EGFR cells CHO cells…”