Journal ArticleDOI
The HER-2/neu Oncogene in Breast Cancer: Prognostic Factor, Predictive Factor, and Target for Therapy
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TLDR
The review will briefly present preliminary data concerning the use of antibody-based therapies directed against the HER-2/neu protein and their potential to become a new modality for breast cancer treatment.Abstract:
The HER-2/neu oncogene encodes a transmembrane tyrosine kinase receptor with extensive homology to the epidermal growth factor receptor. HER-2/neu has been widely studied in breast cancer. In this review, the association of HER-2/neu gene and protein abnormalities studied by Southern and slot blotting, immunohistochemistry, enzyme immunoassays, and fluorescence in situ hybridization with prognosis in breast cancer is studied in depth by review of a series of 47 published studies encompassing more than 15,000 patients. The relative advantages of gene amplification assays and frozen/fresh tissue immunohistochemistry over paraffin section immunohistochemistry are discussed. 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 potential value of HER-2/neu status for the prediction of response to therapy in breast cancer is presented in the light of a series of recently published studies showing a range of impact on the outcome of patients treated with hormonal, cytotoxic, and radiation therapies. The evidence that HER-2/neu gene and protein abnormalities in breast cancer predict resistance to tamoxifen therapy and relative sensitivity to chemotherapy regimens including adriamycin is presented. The review will also evaluate the status of serum-based testing for circulating the HER-2/neu receptor protein and its ability to predict disease outcome and therapy response. In the final section, the review will briefly present preliminary data concerning the use of antibody-based therapies directed against the HER-2/neu protein and their potential to become a new modality for breast cancer treatment. The recently presented phase III clinical trial evidence that systemic administration of anti-HER2 antibodies (Herceptin®), alone and in combination with cytotoxic chemotherapy in patients with HER-2/neu overexpressing primary tumors, can increase the time to recurrence and overall response rates in metastatic breast cancer is reviewed.read more
Citations
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Journal ArticleDOI
Untangling the ErbB signalling network
Yosef Yarden,Mark X. Sliwkowski +1 more
TL;DR: When epidermal growth factor and its relatives bind the ErbB family of receptors, they trigger a rich network of signalling pathways, culminating in responses ranging from cell division to death, motility to adhesion.
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Immunofluorescent labeling of cancer marker Her2 and other cellular targets with semiconductor quantum dots
Xingyong Wu,Hongjian Liu,Jianquan Liu,Kari Haley,Joseph A. Treadway,J. Peter Larson,Nianfeng Ge,Frank Peale,Marcel P. Bruchez +8 more
TL;DR: Using QDs linked to immunoglobulin G and streptavidin to label the breast cancer marker Her2, to stain actin and microtubule fibers in the cytoplasm, and to detect nuclear antigens inside the nucleus indicate that QD-based probes can be very effective in cellular imaging and offer substantial advantages over organic dyes in multiplex target detection.
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Non-coding RNA networks in cancer.
TL;DR: A deeper understanding of the complex networks of interactions that ncRNAs coordinate would provide a unique opportunity to design better therapeutic interventions.
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Structure of the epidermal growth factor receptor kinase domain alone and in complex with a 4-anilinoquinazoline inhibitor.
TL;DR: It is found that the EGFRK activation loop adopts a conformation similar to that of the phosphorylated active form of the kinase domain from the insulin receptor, which is distinguished from all other known receptor tyrosine kinases in possessing constitutive kinase activity without a phosphorylation event within their kinase domains.
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Insights into ErbB signaling from the structure of the ErbB2-pertuzumab complex
Matthew C. Franklin,Kendall D. Carey,Felix Vajdos,Daniel J. Leahy,Abraham M. de Vos,Mark X. Sliwkowski +5 more
TL;DR: The 3.2 A X-ray crystal structure of the extracellular domain of the human epidermal growth factor receptor 2 (ErbB2 or HER2) in a complex with the antigen binding fragment of pertuzumab, an anti-Erb B2 monoclonal antibody, is determined.
References
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Journal ArticleDOI
Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene
Dennis J. Slamon,Gary M. Clark,Steven G. Wong,Wendy J. Levin,Axel Ullrich,William L. McGuire +5 more
TL;DR: Amplification of the HER-2/neu gene was a significant predictor of both overall survival and time to relapse in patients with breast cancer, and had greater prognostic value than most currently used prognostic factors in lymph node-positive disease.
Journal Article
Prognostic and predictive factors in breast cancer by immunohistochemical analysis
TL;DR: Although available studies suggest that estrogen and progesterone receptors might indeed be helpful in making treatment decisions, their clinical usefulness is still controversial, and there are important unresolved technical issues, such as how to prepare the tissue, which reagents to use and, most importantly, how to interpret the results.
Journal ArticleDOI
Phase II study of weekly intravenous recombinant humanized anti-p185HER2 monoclonal antibody in patients with HER2/neu-overexpressing metastatic breast cancer.
José Baselga,Debasish Tripathy,John Mendelsohn,S. Baughman,Christopher C. Benz,L. Dantis,Nancy Sklarin,Andrew D. Seidman,Clifford A. Hudis,J. Moore,Paul Peter Rosen,T. Twaddell,I. C. Henderson,Larry Norton +13 more
TL;DR: RhuMAb HER2 is well tolerated and clinically active in patients with HER2-overexpressing metastatic breast cancers that had received extensive prior therapy and justifies further evaluation of this agent.
Journal ArticleDOI
c-erbB-2 Expression and Response to Adjuvant Therapy in Women with Node-Positive Early Breast Cancer
Hyman B. Muss,Ann D. Thor,Donald A. Berry,Timothy E. Kute,Edison T. Liu,Frederick C. Koerner,Constance Cirrincione,Daniel R. Budman,William C. Wood,Maurice Barcos,I. Craig Henderson +10 more
TL;DR: Patients randomly assigned to the high-dose regimen of adjuvant chemotherapy had significantly longer disease-free and overall survival if their tumors had c-erbB-2 overexpression, a useful marker to identify a subgroup of patients more likely than others to benefit from high doses of chemotherapy.
Journal ArticleDOI
Neu-protein overexpression in breast cancer. Association with comedo-type ductal carcinoma in situ and limited prognostic value in stage II breast cancer.
van de Vijver Mj,Johannes L. Peterse,Wolter J. Mooi,P. Wisman,Lomans J,Otilia Dalesio,Roel Nusse +6 more
TL;DR: It is concluded that neu overexpression may be an early step in the development of a distinct histologic type of carcinoma of the breast, but it could find no association of overeexpression with lymph-node status or tumor recurrence.