c-erbB-2 oncoprotein detected by automated quantitative immunocytochemistry in breast carcinomas correlates with patients' overall and disease-free survival

Charpin, Colette; García, Stéphane; Bouvier, Corinne; Martini, François; Lavaut, Marie‐Noëlle; Allasia, Claude; Bonnier, Pascal; Andrac, L

doi:10.1038/bjc.1997.283

Cited by 35 publications

(11 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Epidermal growth factor receptor overexpression was always associated with poor outcome, manifested in a short overall survival and disease-free interval (Sainsbury et al, 1985;Lewis et al, 1990;Toi et al, 1994;Tsutsui et al, 2002), high metastatic potential (Sainsbury et al, 1987) and negative oestrogen receptor (ER) status (Pilichowska et al, 1997;Tsutsui et al, 2002). The same behaviour was also detected in tumours showing c-erbB-2 gene amplification and/or overexpression, which was marked in high tumour grade as well as short overall survival and disease-free interval (Winstanley et al, 1991;Charpin et al, 1997;Suo et al, 2002).…”

mentioning

confidence: 78%

Expression and co-expression of the members of the epidermal growth factor receptor (EGFR) family in invasive breast carcinoma

et al. 2004

View full text Add to dashboard Cite

The epidermal growth factor receptor (EGFR) family plays an important role in breast carcinogenesis. Much interest has been focused recently on its members because of their potential role as prognostic indicators in breast cancer and their involvement in cancer therapy. We have evaluated more than 1500 cases of invasive breast carcinoma immunohistochemically using tissue microarray technology to examine the expression of EGFR family receptor proteins. We have found that 20.1 and 31.8% of cases were positive for EGFR and c-erbB-2, respectively, and 45 and 45.1% of tumours overexpressed for c-erbB-3 and c-erbB-4, respectively. The expression of either EGFR or c-erbB-2 was associated with other bad prognostic features and with poor outcome. Neither c-erbB-3 nor c-erbB-4 had any association with survival. c-erbB-2 had an independent prognostic effect on overall and disease-free survival (DFS) in all cases, as well as in the subset of breast carcinoma patients with nodal metastases. Several hetero-and homodimeric combinations have been reported between the EGFR members. Those dimers can evoke diverse signal transduction pathways with variable cellular responses. We stratified cases according to their co-expression of receptors into distinct groups with different receptor-positive combinations. Patients whose tumours co-expressed c-erbB-2 and c-erbB-3, as well as those whose tumours coexpressed EGFR, c-erbB-2 and c-erbB-4 showed an unfavourable outcome compared with other groups, while combined c-erbB-3 and c-erbB-4 expression was associated with a better outcome. In cases showing expression of one family member only (homodimers), we found a significant association between c-erbB-4 homodimer-expressing tumours and better DFS. In contrast, patients with c-erbB-2 homodimer-expressing tumours had a significant poorer DFS compared with other cases. These data imply that the combined profile expression patterns of the four receptor family members together provide more accurate information on the tumour behaviour than studying the expression of each receptor individually.

show abstract

mentioning

confidence: 78%

Expression and co-expression of the members of the epidermal growth factor receptor (EGFR) family in invasive breast carcinoma

et al. 2004

View full text Add to dashboard Cite

show abstract

“…In addition to Southern and slot-blotting techniques to evaluate HER2 status in breast cancer, polymerase chain reaction (PCR) methods, and more recently, in situ hybridization (Ross and Fletcher, 1999) have been used. Qualitative and quantitative HER2 protein measurements have been obtained using immunohistochemistry (Allred et al, 1992;Battifora et al, 1991;Berger et al, 1988;Bianchi et al, 1993;Charpin et al, 1997;Dykens et al, 1991;Fernandez et al, 1997;Gusterson et al, 1992;Hartmann et al, 1994;Hieken et al, 1996;Jacquemier et al, 1994;Kallioniemi et al, 1991;Lovekin et al, 1991;Marks et al, 1994;McCann et al, 1991;Molina et al, 1992;Muss et al, 1994;Noguchi et al, 1992;O'Malley et al, 1996;O'Reilly et al, 1991;Paik et al, 1990;Press et al, 1993;Quenel et al, 1995;Rilke et al, 1991;Rosen et al, 1995;Sundblad et al, 1996;Tetu and Brisson 1994;Van de Vijver et al, 1988;Winstanley et al, 1991) on frozen and archival tissues, and Western blotting (Giai et al, 1994;Molina et al, 1992), and enzyme immunoassays Eissa et al, 1997;Hieken et al, 1996) on solubilized tumor extracts. Northern blot has been used to measure the level of specific mRNA (Gia...…”

Section: Her2 Amplification and Overexpression: Prognostic Valuementioning

confidence: 99%

Role of HER2 gene overexpression in breast carcinoma

et al. 2000

View full text Add to dashboard Cite

The HER2 proto-oncogene encodes a transmembrane glycoprotein of 185 kDa (p185(HER2)) with intrinsic tyrosine kinase activity. Amplification of the HER2 gene and overexpression of its product induce cell transformation. Numerous studies have demonstrated the prognostic relevance of p185(HER2), which is overexpressed in 10% to 40% of human breast tumors. Recent data suggest that p185(HER2) is a ligand orphan receptor that amplifies the signal provided by other receptors of the HER family by heterodimerizing with them. Ligand-dependent activation of HER1, HER3, and HER4 by EGF or heregulin results in heterodimerization and, thereby, HER2 activation. HER2 overexpression is associated with breast cancer patient responsiveness to doxorubicin, to cyclophosphamide, methotrexate, and fluorouracil (CMF), and to paclitaxel, whereas tamoxifen was found to be ineffective and even detrimental in patients with HER2-positive tumors. In vitro analyses have shown that the role of HER2 overexpression in determining the sensitivity of cancer cells to drugs is complex, and molecules involved in its signaling pathway are probably the actual protagonists of the sensitivity to drugs. The association of HER2 overexpression with human tumors, its extracellular accessibility, as well as its involvement in tumor aggressiveness are all factors that make this receptor an appropriate target for tumor-specific therapies. A number of approaches are being investigated as possible therapeutic strategies that target HER2: (1) growth inhibitory antibodies, which can be used alone or in combination with standard chemotherapeutics; (2) tyrosine kinase inhibitors (TKI), which have been developed in an effort to block receptor activity because phosphorylation is the key event leading to activation and initiation of the signaling pathway; and (3) active immunotherapy, because the HER2 oncoprotein is immunogenic in some breast carcinoma patients.

show abstract

“…Nor did we see an influence related to tumor size in these patients. Several previous studies have reported associations of positive HER‐2 status with poor prognosis for node‐negative disease (19–21), particularly a study that reported greater precision in the prognostic estimate when considering the size of the tumor (9).…”

Section: Discussionmentioning

confidence: 99%

Variation of the Prognostic Significance of HER-2 Expression in Breast Cancer According to Tumor Size

Swede¹,

Moysich²,

Winston³

et al. 2003

Breast Journal

View full text Add to dashboard Cite

The prognostic importance of HER-2 status in breast cancer has been investigated extensively, but findings have not been uniform across immunohistochemical studies using fixed, paraffin-embedded specimens. We speculate that studies with an overrepresentation of large tumors might not produce evidence for an independent effect of a single marker because breast tumors of larger size tend to exhibit multiple adverse attributes as the malignancy advances through the metastatic cascade. Further, it has been posited that results from certain studies of biologic markers might be generalizable only to larger tumors because tumor repositories tend to house a disproportionate number of larger tumors. To test our hypothesis that the prognostic effect of HER-2 status might be modified by the size of the tumor, we conducted a survival analysis of a nested case-case sample of 156 women diagnosed with primary breast cancer from 1983 to 1995. Relative risks (RRs) and confidence intervals (CIs) for recurrence in relation to HER-2 status were estimated using a multivariate Cox proportional hazards model. Immunohistochemistry of archival tissue was used to detect HER-2 expression. Positive HER-2 status was associated with recurrence (RR = 4.24, 95% CI 1.30-13.78) among patients with axillary lymph node-positive involvement. This analysis identified an interaction (p < 0.01) between tumor size and overexpression. Stratification by tumor size revealed an increased risk of recurrence associated with HER-2-positive tumors that were

show abstract

c-erbB-2 oncoprotein detected by automated quantitative immunocytochemistry in breast carcinomas correlates with patients' overall and disease-free survival

Cited by 35 publications

References 20 publications

Expression and co-expression of the members of the epidermal growth factor receptor (EGFR) family in invasive breast carcinoma

Expression and co-expression of the members of the epidermal growth factor receptor (EGFR) family in invasive breast carcinoma

Role of HER2 gene overexpression in breast carcinoma

Variation of the Prognostic Significance of HER-2 Expression in Breast Cancer According to Tumor Size

Contact Info

Product

Resources

About