Epidermal growth factor receptor (EGFr) as a marker for poor prognosis in node-negative breast cancer patients: Neu and tamoxifen failure

Nicholson, S; Wright, Christopher; Sainsbury, Jrc; Halcrow, P.; Kelly, Peter; Angus, Brian; FarnVon, John R.; Harris, Adrian L.

doi:10.1016/0960-0760(90)90424-j

Cited by 133 publications

(73 citation statements)

References 12 publications

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“…Within the carcinomas staining was found to be heterogeneous and predominantly cytoplasmic with membrane staining seen in less than 1% of cases ( Figure 1). The majority of tumours in both series exhibited moderate immunoreactivity but a substantial proportion in both the primary and advanced series exhibited strong positivity (Figure 2 (Sainsbury et al, 1985(Sainsbury et al, , 1987Nicholson et al, 1990 (Slamon et al, 1987). Further studies have supported this association (Wright et al, 1989;Gullick et al, 1991;Lovekin et al, 1991).…”

Section: Resultsmentioning

confidence: 90%

“…Expression of both EGFR and the c-erbB-2 oncoproteins have been associated with established prognostic indicators and a poorer prognosis in human breast carcinoma (Sainsbury et al, 1985(Sainsbury et al, , 1987Nicholson et al, 1990;Grimaux et al, 1989;Walker et al, 1989;Wright et al, 1989;Gullick et al, 1991;Slamon et al, 1987). The sequence homology of the c-erbB-3 oncoprotein to the EGFR and cerbB-2 oncoprotein has lead to interest in c-erbB-3 expression in breast cancer.…”

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confidence: 99%

See 1 more Smart Citation

C-erbB-3 in human breast carcinoma: expression and relation to prognosis and established prognostic indicators

Travis

Pinder²,

Robertson³

et al. 1996

Br J Cancer

117

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Section: Resultsmentioning

confidence: 90%

mentioning

confidence: 99%

C-erbB-3 in human breast carcinoma: expression and relation to prognosis and established prognostic indicators

Travis

Pinder²,

Robertson³

et al. 1996

Br J Cancer

117

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“…A total of 15 studies were identified that met the meta-analysis inclusion criteria (12 -26). The studies by Nicholson et al (12) and Leitzel et al (15) were excluded because subsequent articles containing updated results were included in the meta-analysis, whereas the study by Bezwoda (25) was excluded because it contained insufficient information and it was not possible to get further details. All the remaining 12 studies were used in the pooled analysis (2,379 patients).…”

Section: Resultsmentioning

confidence: 99%

A Meta-Analysis on the Interaction between HER-2 Expression and Response to Endocrine Treatment in Advanced Breast Cancer

Laurentiis¹,

Arpino

Massarelli

et al. 2005

Clinical Cancer Research

310

195

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Purpose: Experimental data suggest a complex cross-talk between HER-2 and estrogen receptor, and it has been hypothesized that HER-2-positive tumors may be less responsive to certain endocrine treatments. Clinical data, however, have been conflicting. We have conducted a metaanalysis on the interaction between the response to endocrine treatment and the overexpression of HER-2 in metastatic breast cancer. Experimental Design: Studies have been identified by searching the Medline, Embase, and American Society of Clinical Oncology abstract databases. Selection criteria were (a) metastatic breast cancer, (b) endocrine therapy (any line of treatment), and (c) evaluation of HER-2 expression (any method). For each study, the relative risk for treatment failure for HER-2-positive over HER-2-negative patients with 95% confidence interval was calculated as an estimate of the predictive effect of HER-2. Pooled estimates of the relative risk were computed by the MantelHaenszel method. Results: Twelve studies (n = 2,379 patients) were included in the meta-analysis. The overall relative risk was 1.42 (95% confidence interval, 1.32-1.52; P < 0.00001; test for heterogeneity = 0.380). For studies involving tamoxifen, the pooled relative risk was 1.33 (95% confidence interval, 1.20-1.48; P < 0.00001; test for heterogeneity = 0.97); for studies involving other hormonal drugs, a pooled relative risk of 1.49 (95% confidence interval, 1.36-1.64; P < 0.00001; test for heterogeneity = 0.08) was estimated. A second meta-analysis limited to tumors that were either estrogen receptor positive, estrogen receptor unknown, or estrogen receptor negative/progesterone receptor positive yielded comparable results. Conclusions: HER-2-positive metastatic breast cancer is less responsive to any type of endocrine treatment. This effect holds in the subgroup of patients with positive or unknown steroid receptors.

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“…38 Several clinical studies have also shown an association between HER-2 overexpression and drug resistance to alkylating agents, anthracyclines and CMF-like regimens. 32,[39][40][41] Additional studies have shown a correlation between HER-2 overexpression and tamoxifen [42][43][44][45] and hormone therapy 25,46 resistance in breast cancer. Alternatively, the poor prognosis associated with HER-2 overexpression may occur as a result of increased proliferation and metastasis as indicated by other studies.…”

Section: Discussionmentioning

confidence: 99%

Expression of C-erbB-2/HER-2 in patients with metastatic breast cancer undergoing high-dose chemotherapy and autologous blood stem cell support

Bewick

Chadderton

Conlon

et al. 1999

Bone Marrow Transplant

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Summary:C-erbB-2/HER-2 (designated HER-2) is overexpressed in both primary and metastatic breast cancer and predicts poor prognosis. We investigated the expression of HER-2 in patients with metastatic breast cancer undergoing high-dose chemotherapy (HDCT) with autologous blood stem cell (ABSC) support and correlated the presence (positive) or absence (negative) of HER-2 overexpression in these patients with response to treatment, progression-free survival (PFS) and overall survival (OS). The level of HER-2 expression was analyzed in 57 patients with metastatic breast cancer undergoing HDCT with ABSC support. Plasma from peripheral blood was taken at three different time points during the course of treatment and was analyzed using an enzyme immunoassay (EIA) to detect circulating levels of the extracellular portion of HER-2. HER-2 levels were elevated (Ͼ0.2 U/mg protein) in 27/57 (47.4%) patients at one or more time points during treatment. The level of HER-2 varied during the course of treatment. Following induction chemotherapy (ICT), five patients who were negative initially, showed overexpression of HER-2. Three patients overexpressed HER-2 only after HDCT/ABSC. Response to treatment was similar in patients independent of plasma HER-2 levels. Overexpression of HER-2 was associated with a significantly shorter PFS (P = 0.004, log rank) and OS (P = 0.003, log rank) after HDCT/ABSC. HER-2 overexpression, patient age, estrogen receptor status, progesterone receptor status, and previous hormone treatment were assessed by univariate and multivariate analysis. Univariate analysis determined that only HER-2 overexpression correlated significantly with decreases in progression free survival (P = 0.005, Cox regression). Decreased overall survival correlated significantly with HER-2 overexpression (P = 0.004) and decreased expression of both estrogen receptor (P = 0.032) and progesterone receptor (P = 0.039). In multivariate analysis of these variables, only HER-2 expression levels proved to be of independent statistical significance in predicting outcome for both PFS (P = 0.007) and OS Correspondence: Dr S Glück, Depts Oncology, Medicine, and Pharmacology and Therapeutics, Faculty of Medicine, University of Calgary, Tom Baker Cancer Centre, 1331, 29th Street NW, Calgary, Alberta, Canada Received 18 August 1998; accepted 5 May 1999 (P = 0.002). These results suggest that overexpression of HER-2, measured by EIA in plasma may predict a shorter PFS and OS in patients with metastatic breast cancer treated with HDCT and ABSC support.

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Epidermal growth factor receptor (EGFr) as a marker for poor prognosis in node-negative breast cancer patients: Neu and tamoxifen failure

Cited by 133 publications

References 12 publications

C-erbB-3 in human breast carcinoma: expression and relation to prognosis and established prognostic indicators

C-erbB-3 in human breast carcinoma: expression and relation to prognosis and established prognostic indicators

A Meta-Analysis on the Interaction between HER-2 Expression and Response to Endocrine Treatment in Advanced Breast Cancer

Expression of C-erbB-2/HER-2 in patients with metastatic breast cancer undergoing high-dose chemotherapy and autologous blood stem cell support

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