Oncogenes and Male Breast Carcinoma: c-erbB-2 and p53 Coexpression Predicts a Poor Survival

Pich, Achille; Margaria, E; Chiusa, Luigi

doi:10.1200/jco.2000.18.16.2948

Cited by 76 publications

(52 citation statements)

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“…Despite this apparent heterogeneity of the predominant clone measured by ploidy status, in each metastatic site, the HER-2/neu status was consistent between primary tumors and their corresponding metastases [180]. HER-2/neu amplification and overexpression has been associated with adverse outcome in some studies of male breast carcinoma [181][182][183][184], but not in others [185][186][187]. Finally, low level HER-2/neu overexpression has been identified in benign breast disease biopsies and associated with a greater risk of subsequent invasive breast cancer [188].…”

Section: Her-2/neu Expression and Breast Pathologymentioning

confidence: 99%

The HER-2/neu Gene and Protein in Breast Cancer 2003: Biomarker and Target of Therapy

et al. 2003

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The HER-2/neu oncogene encodes a transmembrane tyrosine kinase receptor with extensive homology to the epidermal growth factor receptor. In this review, the association of HER-2/neu gene and protein abnormalities with prognosis and response to therapy with trastuzumab and to other therapies in breast cancer is presented. By considering a series of 80 published studies encompassing more than 25,000 patients, the relative advantages and disadvantages of Southern blotting, polymerase chain reaction amplification, andThe Oncologist 2003;8:307-325 www.TheOncologist.comCorrespondence: Jeffrey S. Ross, M.D., Albany Medical College, Department of Pathology, Mail Code 81, 47 New Scotland Avenue, Albany, New York 12208, USA. Telephone: 518-262-5461; Fax: 518-262-8092; e-mail: rossj@mail.amc.edu Received February 5, 2003; accepted for publication April 28, 2003. ©AlphaMed Press 1083-7159/2003 The Oncologist ® LEARNING OBJECTIVESAfter completing this course, the reader will be able to:1. Define the historical background and biological basis of the discovery of the HER-2/neu gene and its first use as a prognostic factor in breast cancer.2. Recall the uses of HER-2/neu testing prior to the approval of trastuzumab including the impact on anthracycline adjuvant and first-line chemotherapy responses.3. Explain the basic principles of all the HER-2/neu tests in clinical practice: IHC, FISH, Southern blot, PCR, tissue ELISA, and serum ELISA.4. Contrast the pros and cons and uses and limitations of the IHC versus the FISH approach to HER-2/neu testing.5. Critique the most recent data comparing IHC with FISH for the prediction of response to single-agent trastuzumab and trastuzumab in combination with standard chemotherapy for advanced metastatic breast cancer.6. Describe the HER-2/neu expression patterns in all types of breast conditions, including in situ carcinoma, lobular versus ductal carcinoma, Paget's disease, male breast cancer, breast sarcomas, and benign breast disorders.Access and take the CME test online and receive one hour of AMA PRA category 1 credit at CME.TheOncologist.com CME CME This material is protected by U.S. Copyright law. Unauthorized reproduction is prohibited. For reprints contact: Reprints@AlphaMedPress.com Ross, Fletcher, Linette et al. 308 HER-2/NEU GENE (C-ERBB-2)The human epidermal growth factor receptor 2 (HER-2)/neu (c-erbB-2) gene is localized to chromosome 17q and encodes a transmembrane tyrosine kinase receptor protein that is a member of the epidermal growth factor receptor (EGFR) or HER family ( Fig. 1) [1]. This family of receptors is involved in cell-to-cell and cell-to-stroma communication primarily through a process known as signal transduction, in which external growth factors, or ligands, affect the transcription of various genes by phosphorylating or dephosphorylating a series of transmembrane proteins and intracellular signaling intermediates, many of which possess enzymatic activity. Signal propagation occurs as the enzymatic activity of one protein turns on the enzymat...

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Section: Her-2/neu Expression and Breast Pathologymentioning

confidence: 99%

The HER-2/neu Gene and Protein in Breast Cancer 2003: Biomarker and Target of Therapy

et al. 2003

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“…Despite this apparent heterogeneity of the predominant clone measured by ploidy status, in each metastatic site the HER-2/neu status was consistent between primary tumors and their corresponding metastases (42). HER-2/neu amplification and overexpression has been associated with adverse outcome in some studies of male breast carcinoma (43)(44)(45)(46), but not in others (47)(48)(49)). Finally, low-level HER-2/neu overexpression has been identified in benign breast disease biopsies and associated with an increased risk of subsequent invasive breast cancer (50).…”

Section: Fig 2 the Her (Erb) Gene Familymentioning

confidence: 99%

Targeted Therapy in Breast Cancer

Ross

Fletcher

Bloom³

et al. 2004

Molecular & Cellular Proteomics

259

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The HER-2/neu oncogene, a member of the epidermal growth factor receptor or erb gene family, encodes a transmembrane tyrosine kinase receptor that has been linked to prognosis and response to therapy with the anti-HER-2-humanized monoclonal antibody, trastuzumab (Herceptin, Genentech, South San Francisco, CA) in patients with advanced metastatic breast cancer. HER-2/neu status has also been tested for its ability to predict the response of breast cancer to other therapies including hormonal therapies, topoisomerase inhibitors, and anthracyclines. This review includes an analysis of 80 published studies encompassing more than 25,000 patients designed to consider the relative advantages and disadvantages of the various methods of measuring HER-2/neu in clinical breast cancer specimens. Southern blotting, PCR amplification detection, and fluorescence in situ hybridization assays designed to detect HER-2/neu gene amplification are compared with HER-2/neu protein overexpression assays performed by immunohistochemical techniques applied to frozen and paraffin-embedded tissues and enzyme immunoassays performed on tumor cytosols. The significance of HER-2/neu overexpression in ductal carcinoma in situ and the HER-2/neu status in uncommon female breast conditions and male breast cancer are also considered. The role of HER-2/neu testing for the prediction of response to trastuzumab therapy in breast cancer is reviewed along with the current studies designed to test whether HER-2/neu status can predict the response to standard and newer hormonal therapies, cytotoxic chemotherapy, and radiation. The review will also evaluate the status of serum-based testing for circulating HER-

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“…Numerous studies of Her2-neu gene and protein expression correlate with poor prognosis in female breast cancers, especially in node-positive patients (30), but few data are available in the male counterpart. A few studies with limited numbers of patients show that Her2-neu protein overexpression as measured by immunohistochemistry is present Grade 1 8 0 8 0 2 6 2 1 5 0 8 2 27 1 24 4 6 22 3 13 12 3 25 3 23 2 NS 16 in 1.7-45% of male breast carcinoma patients, but survival analysis is limited by small sample size (21,22,(31)(32)(33) and by no clear association with survival. A recent breast cancer therapy directed against the Her2-neu (anti-Her2 antibodies-Herceptin, generic name trastuzamab) is undergoing clinical trial and shows potential benefit in the treatment of metastatic disease, either as a single agent or in combination with other chemotherapy (34).…”

Section: Figure 2 the Disease-free Survival Of Mbc Patients In Four mentioning

confidence: 99%

Male Breast Carcinoma: Correlation of ER, PR, Ki-67, Her2-Neu, and p53 with Treatment and Survival, a Study of 65 Cases

et al. 2002

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Male breast cancer is rare, and experience of it in any single institution is limited. Our current understanding regarding its biology, natural history, and treatment strategies has been extrapolated from its female counterpart. The aim of this study is to evaluate the expression patterns of estrogen receptor (ER), progesterone receptor (PR), MiB1 (Ki67), Her-2/neu (c-erbB2), and p53 and to correlate them with the prognosis, presentation, staging, management, and survival/outcome in male breast carcinoma identified through the Veterans Administration nationwide cancer registry. Sixty-five cases of male breast cancer were reviewed for classification. Tumor blocks were requested from each institution for immunohistochemical staining and evaluation of ER, PR, p53, Her2-neu, and MiB1. Seventeen ageand disease-matched male veteran patients with breast gynecomastia were used as controls. Traditional prognostic data were collected for comparison with female breast cancers (i.e., age, lymph node status, clinical staging, tumor size, histological grade, and disease-free and overall survival). Male breast carcinoma had worse disease-free survival than controls (P ‫؍‬ .03). The clinical stage regardless of tumor size or lymph node metastasis was the single most significant prognostic factor (P < .0001). ER-positive patients appeared to have a better survival than did ER-negative patients (P ‫؍‬ .03, univariate; P not significant in multivariate) and did not benefit from treatment with tamoxifen (P ‫؍‬ .0027, univariate; P ‫؍‬ .42, multivariate). MiB1 and PR expressions did not correlate with treatment or survival, and p53 was associated with shorter disease free survival (P ‫؍‬ .07, univariate; P ‫؍‬ .047, multivariate). Stage for stage, Her2-neu was associated with shorter disease-free survival (P < .0001) and correlated with positive lymph nodes (P ‫؍‬ .08). Male breast carcinoma is rare, with an estimated 1,000 to 1,400 new cases per year (1). The tumor phenotypic alterations are not well studied, and experience is mainly inferred from that of female breast cancer. Although both diseases have similarities, there are notable differences in risk factors, prognosis, and survival. Reported differences between male and female breast carcinoma have been noted, and male breast carcinoma has a tendency to present at higher clinical stages and with more lymph node metastases (2-4). Many molecular markers are available for the better understanding of female breast cancer tumorigenesis and disease progression and possibly to guide treatment. How-

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Oncogenes and Male Breast Carcinoma: c-erbB-2 and p53 Coexpression Predicts a Poor Survival

Abstract: Overexpression of c-myc, c-erbB-2, and p53 proteins may be regarded as an additional prognostic factor in MBC. The combination of c-erbB-2 and p53 immunoreactivity can stratify patients into different risk groups.

Cited by 76 publications

References 53 publications

The HER-2/neu Gene and Protein in Breast Cancer 2003: Biomarker and Target of Therapy

The HER-2/neu Gene and Protein in Breast Cancer 2003: Biomarker and Target of Therapy

Targeted Therapy in Breast Cancer

Male Breast Carcinoma: Correlation of ER, PR, Ki-67, Her2-Neu, and p53 with Treatment and Survival, a Study of 65 Cases

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