Dual immunocytochemical analysis of oestrogen and epidermal growth factor receptors in human breast cancer

Sharma, Ajay; Horgan, Kieran; Douglas-Jones, Anthony; McClelland, Richard Andrew; Gee, Julia Margaret Wendy; Nicholson, Robert Ian

doi:10.1038/bjc.1994.203

Cited by 47 publications

(15 citation statements)

References 30 publications

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“…These events thus appear to be critical in the generation of several forms of acquired endocrine resistance and insensitivity. Excitingly, the phenotypic characteristics of breast tumours from patients with hormone-resistant disease in many ways parallel these experimental data (Nicholson et al 1993a, 1994a,b, 1997a,b, Gee et al 2001a. Furthermore, our in vitro data also show that such endocrine-resistant or -insensitive cells are highly sensitive to the EGFR-selective tyrosine kinase inhibitor, ZD 1839 (Iressa; Astra Zeneca).…”

Section: Introductionmentioning

confidence: 72%

“…Of particular interest was the observation that predominance of the protein was associated with elevated proliferative capacity, disease progression and extremely poor patient prognosis (Nicholson et al 1993a(Nicholson et al , 1994a(Nicholson et al , 1997a. Since that time, a universal finding has been that expression of the EGFR protein is highly variable within the breast cancer population.…”

Section: Egfr/c-erbb2 Signalling and Endocrine Response In Clinical Bmentioning

confidence: 99%

“…In contrast to IGFs, EGFR ligands are poor inducers of the growth of hormone-sensitive cells, where at best they promote growth responses which are additive (but not synergistic) with oestradiol. Finally, there are obvious inverse associations between these receptor tyrosine kinase receptors and ER expression in clinical and experimental samples (Nicholson et al 1993a, 1994a, 1997a,b, Sharma et al 1994a. In parallel, there is merely low expression of the EGFR ligand TGF-α (Nicholson et al 1994b), with activation of the important downstream signalling target for EGFR, mitogen-activated protein (MAP) kinase, also minimal in ER-positive disease both in the clinic (Gee et al 2001a) and in vitro (McClelland et al 2001).…”

Section: Er Signalling and Growth Factors In Hormone-sensitive Breastmentioning

confidence: 99%

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Modulation of epidermal growth factor receptor in endocrine-resistant, oestrogen receptor-positive breast cancer.

Nicholson

Hutcheson²,

Harper³

et al. 2001

Endocrine-Related Cancer

133

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There is an increasing body of evidence demonstrating that growth factor networks are highly interactive with oestrogen receptor (ER) signalling in the control of breast cancer growth. As such, tumour responses to anti-hormones are likely to be a composite of the ER and growth factor inhibitory activity of these agents. The current article examines the modulation of growth factor networks during endocrine response, and presents in vitro and clinical evidence that epidermal growth factor receptor signalling, maintained in either an ER-dependent or -independent manner, is critical to antihormonal-resistant breast cancer cell growth. The considerable potential of the epidermal growth factor receptor-selective tyrosine kinase inhibitor, ZD 1839 (Iressa; AstraZeneca) to efficiently treat, and perhaps even prevent, endocrine-resistant breast cancer is highlighted.

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Section: Introductionmentioning

confidence: 72%

Section: Egfr/c-erbb2 Signalling and Endocrine Response In Clinical Bmentioning

confidence: 99%

Section: Er Signalling and Growth Factors In Hormone-sensitive Breastmentioning

confidence: 99%

See 1 more Smart Citation

Modulation of epidermal growth factor receptor in endocrine-resistant, oestrogen receptor-positive breast cancer.

Nicholson

Hutcheson²,

Harper³

et al. 2001

Endocrine-Related Cancer

133

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“…The protooncogene Ras, the downstream mediator of growth factor receptor activation, is overexpressed in -70% of breast cancer (14,15), further implicating growth factor signaling mechanisms in breast cancer. Doublelabel immunohistochemical detection of ER and EGFR in breast tumor specimens and breast cancer cell lines confirms the inverse correlation of expression (16)(17)(18). Furthermore, in ER+/EGFR+ tumors, individual tumor cells express high levels of only ER or EGFR, but never both (16,17).…”

Section: Iipmentioning

confidence: 68%

“…Doublelabel immunohistochemical detection of ER and EGFR in breast tumor specimens and breast cancer cell lines confirms the inverse correlation of expression (16)(17)(18). Furthermore, in ER+/EGFR+ tumors, individual tumor cells express high levels of only ER or EGFR, but never both (16,17). The…”

Section: Iipmentioning

confidence: 68%

Role of Raf-1 Signaling in Breast Cancer - Progression to Estrogen Independent Growth

El-Ashry¹

1998

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

et al. 1996

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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...

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Dual immunocytochemical analysis of oestrogen and epidermal growth factor receptors in human breast cancer

Cited by 47 publications

References 30 publications

Modulation of epidermal growth factor receptor in endocrine-resistant, oestrogen receptor-positive breast cancer.

Modulation of epidermal growth factor receptor in endocrine-resistant, oestrogen receptor-positive breast cancer.

Role of Raf-1 Signaling in Breast Cancer - Progression to Estrogen Independent Growth

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

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