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...
The testing of newly diagnosed breast cancer specimens for HER-2/neu status has achieved "standard of practice" status for the management of breast cancer in the United States. The discussion as to the best method to determine HER-2/neu status in these samples continues, with the fluorescence in situ hybridization method gaining popularity owing to the recent evidence that it, in comparison with immunohistochemical analysis, might more accurately predict clinical responses to trastuzumab-based therapies. With trastuzumab achieving excellent results in the treatment of HER-2/neu-positive advanced disease and under extensive evaluation in major clinical trials for its potential efficacy when used at earlier clinical stages, the potential role(s) for HER-2/neu testing as a predictor of response to other therapies being resolved by large prospective clinical outcome studies, and the more convenient gene-based chromogenic in situ hybridization technique "waiting in the wings," the saga of HER-2/neu testing in breast cancer will continue to unfold over the next several years.
Nevus lipomatosus cutaneus superficialis (NLCS) is a rare developmental anomaly characterized by isolated ectopic mature adipose tissue in the dermis. We describe a child with a NLCS present from birth that was growing in size. The lesion was removed by simple excision and has not recurred.
BackgroundSeveral West African countries are unlikely to achieve the recommended Global Vaccine Action Plan (GVAP) immunisation coverage and dropout targets in a landscape beset with entrenched intra-country equity gaps in immunisation. Our aim was to assess and compare the immunisation coverage, dropout and equity gaps across 15 West African countries between 2000 and 2017.MethodsWe compared Bacille Calmette Guerin (BCG) and the third dose of diphtheria–tetanus–pertussis (DTP3) containing vaccine coverage between 2000 and 2017 using the WHO and Unicef Estimates of National Immunisation Coverage for 15 West African countries. Estimated subregional median and weighted average coverages, and dropout (DTP1–DTP3) were tracked against the GVAP targets of ≥90% coverage (BCG and DTP3), and ≤10% dropouts. Equity gaps in immunisation were assessed using the latest disaggregated national health survey immunisation data.ResultsThe weighted average subregional BCG coverage was 60.7% in 2000, peaked at 83.2% in 2009 and was 65.7% in 2017. The weighted average DTP3 coverage was 42.3% in 2000, peaked at 70.3% in 2009 and was 61.5% in 2017. As of 2017, 46.7% of countries (7/15) had met the GVAP targets on DTP3 coverage. Average weighted subregional immunisation dropouts consistently reduced from 16.4% in 2000 to 7.4% in 2017, meeting the GVAP target in 2008. In most countries, inequalities in BCG, and DTP3 coverage and dropouts were mainly related to equity gaps of more than 20% points between the wealthiest and the poorest, high coverage regions and low coverage regions, and between children of mothers with at least secondary education and those with no formal education. A child’s sex and place of residence (urban or rural) minimally determined equity gaps.ConclusionsThe West African subregion made progress between 2000 and 2017 in ensuring that its children utilised immunisation services, however, wide equity gaps persist.
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