The HER-2/neu oncogene: prognostic factor, predictive factor and target for therapy

Ross, Jeffrey S.; Fletcher, Jonathan A.

doi:10.1006/scbi.1998.0083

Cited by 390 publications

(408 citation statements)

References 73 publications

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“…Equally important is the predictive role of this marker in identifying patients that will or will not respond to hormonal or some chemotherapeutic regimens. The significance of HER-2/neu as a prognostic or predictive marker in breast cancer has been addressed in two literature reviews (1,2). The role of HER-2/neu has been extended with the release of Herceptin, a humanized antibody against HER-2/ neu that is being used to treat breast cancer patients (3).…”

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confidence: 99%

“…There is also great variation in the published data vis-a-vis the scoring systems and the positive cut off points used (1,2). HER-2/neu can be measured in different ways: 1) Oncoprotein over-expression: This could be performed by immunohistochemistry (IH) on either frozen or paraffin embedded tissue sections using monoclonal or polyclonal antibodies to the 185 kd protein or the phosphorylated product; by ELISA (using cytosol or serum) or by Western blot.…”

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Defining a Test for HER-2/neu Evaluation in Breast Cancer in the Diagnostic Setting

et al. 2001

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In breast cancer amplification of the HER-2/neu oncogene and over-expression of the protein product is associated with poor prognosis, predicts response to some chemotherapeutic regimens and is the target for Herceptin treatment. To date there are several methods to assess the amplification/overexpression of HER-2/neu with each having advantages and disadvantages. We have studied amplification and over-expression of HER-2/neu in 250 consecutive cases of breast cancer (220 invasive and 30 in situ carcinomas) presenting to the Department of Pathology at Women's College Campus of Sunnybrook and Women's College Health Sciences Center. Thirty percent of the invasive carcinomas were node positive. HER-2/neu protein overexpression was assessed by immunohistochemistry (IH) using antibody CB11 and amplification of the gene by differential PCR. The percentage of tumor cells showing CB11 staining was determined and the most significant cut off point for positivity was >10% moderate or strong complete membranous staining. The gene was considered amplified if the density score of the product was >2. There was 94% concordance between the two methods (P value .0001). Both methods were positive in 16% of cases and negative in 78% of cases. Discrepant cases were examined by FISH which confirmed the IH results in 9/11 invasive carcinomas. These results show that there is excellent concordance between IH and PCR. However, immunohistochemistry is easier to perform and cheaper than PCR and could be used in routine assessment of HER-2/neu in breast cancer patients.

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Defining a Test for HER-2/neu Evaluation in Breast Cancer in the Diagnostic Setting

et al. 2001

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“…6,8,9 Moreover, the ERBB2 oncogene has recently received attention as a target for antibody-based therapy. 7 MBC is a rare disease representing only 1% of all breast cancer cases, but does have clinical importance especially in families with BRCA2 mutations where 11% of breast carcinomas occur in men.…”

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“…15 Although only a single tumor with ERBB2 amplification was found, we decided to evaluate the ERBB2 protein expression levels because of the clinical significance of this gene in FBC. 6,7 The number of male breast tumors with ERBB2 overexpression was also low (4%). Several previous studies have assessed ERBB2 overexpression by IHC in MBC with variable results.…”

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Frequent amplification and overexpression of CCND1 in male breast cancer

Bärlund

Kuukasjärvi

Syrjäkoski

et al. 2004

Intl Journal of Cancer

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Genetic events underlying the pathogenesis of breast cancer have been studied extensively and several clinically significant markers have been identified. For example, amplification and overexpression of the ERBB2 oncogene is associated with poor prognosis in breast cancer and ERBB2 serves as a target for antibody-based therapy. Current knowledge on the pathogenesis of male breast cancer (MBC) is limited. The purpose of our study was to investigate the potential relevance of a series of genes known to be amplified in female breast cancer (FBC) in a the development and pathogenesis of MBC. To this end, we applied fluorescence in situ hybridization and immunohistochemistry to the analysis of 128 breast tumors from males. Amplification of ERBB2, MYC, PPM1D and ZNF217 was detected rarely (1-2% of tumors) indicating a considerably lower amplification frequency than in FBC. CCND1 amplification was observed in 12% of cases, being in good concordance with findings from FBC. In addition, CCND1 overexpression was detected in 63% of tumors and was associated with ER positivity (p < 0.0001). Our results indicate distinct differences in the genetic basis of MBC and FBC and suggest that marked differences exist in the pathogenesis of these diseases. The lack of ERBB2 involvement was especially unexpected and implies that ERBB2-targeted therapies are unlikely to be beneficial in MBC. Furthermore, the high frequency of hormone receptor positivity and the association between ER positivity and CCND1 overexpression supports the notion that hormonal regulation is likely to be essential for the development of MBC. © 2004 Wiley-Liss, Inc. Key words: male breast cancer; gene amplification; CCND1; tissue microarrayMale breast cancer (MBC) is a rare disease, representing Ͻ1% of all breast cancers and Ͻ1% of all cancers in men. 1,2 All histological types of breast cancer have been identified in men, with infiltrating ductal carcinoma representing about 80% of cases. Similarly to FBC, hormonal, genetic, and environmental factors are involved in the etiology of MBC. 3 Conditions associated with increased estrogen or decreased androgen levels, such as Klinefelter syndrome and testicular disorders, predispose to MBC. 1 Particularly, the Klinefelter syndrome, characterized by 47,XXY karyotype, is associated with a 50-fold increase in breast cancer risk. 4 The genetic factor most clearly associated with MBC is BRCA2 germline mutation and its frequency in men with breast cancer varies considerably (4 -40%) depending on the population investigated. 3,5 Germline BRCA1 mutations are also found in male breast cancer patients. 5 The possible role and clinical utility of oncogene alterations have been widely investigated in FBC. The most extensively studied is the ERBB2 oncogene that belongs to the epidermal growth factor receptor family. ERBB2 is amplified and overexpressed in 10 -34% of FBC and has been shown to have prognostic and predictive value. 6 Targeted therapy against ERBB2 is currently undergoing clinical trials and shows potential benefit...

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Molecular markers as prognostic factors for local recurrence and radioresistance in head and neck squamous cell carcinoma

Smith

Haffty

1999

Radiat. Oncol. Investig.

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The HER-2/neu oncogene: prognostic factor, predictive factor and target for therapy

Cited by 390 publications

References 73 publications

Defining a Test for HER-2/neu Evaluation in Breast Cancer in the Diagnostic Setting

Defining a Test for HER-2/neu Evaluation in Breast Cancer in the Diagnostic Setting

Frequent amplification and overexpression of CCND1 in male breast cancer

Molecular markers as prognostic factors for local recurrence and radioresistance in head and neck squamous cell carcinoma

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