Breast cancer trastuzumab

Dybdal N, Leiberman G, Anderson S, et al. Determination of HER2 gene amplification by fluorescence in situ hybridization and concordance with the clinical trials immunohistochemical assay in women with metastatic breast cancer evaluated for treatment with trastuzumab. Breast Cancer Res. Treat. 2005 93 3-11. 

Recombinant humanized monoclonal antibodies have been used recently to target antigens that are preferentially located on cancer cells. Examples include trastuzumab and rituximab which are used to treat HER2 positive breast cancer and B-cell type lymphomas, respectively. Unwanted side effects include anaphylactic reactions. 

Trastuzumab specifically binds the extracellular domain of HER-2 that is found overexpressed on the membrane of cancer cells in 15-20% of patients with breast cancer. It has been approved in HER-2 overexpressing (HER-2 +++ or FISH +) breast cancers. 

Trastuzumab (Herceptin ) Roche mAb HER-2 HER-2 overexpressing breast cancer in the adjuvant and metastatic settings... 

Trastuzumab (Herceptin) Humanized antibody, IgGi ErbB2/Her-2 Receptor down-regulation Breast cancer... 

Discuss the role of trastuzumab in the management of early- and advanced-stage breast cancer. 

Yeon CH, Pegram MD. Anti-erbB-2 antibody trastuzumab in the treatment of HER2-amplified breast cancer. Invest New Drugs 2005 23 391-409. 

Clark, A.S., West, K., Streicher, S., and Dennis, P.A. 2002. Constitutive and inducible Akt activity promotes resistance to chemotherapy, trastuzumab, or tamoxifen in breast cancer cells Mol Cancer Ther 1 707-717. 

Bartlett JM. Pharmacodiagnostic testing in breast cancer focus on HER2 and trastuzumab therapy. Am. J. Pharmacogenomics 2005 5 303-315. 

Standardization of IHC/ICC has been a critical issue for more than three decades, especially with the advances in targeted therapy such as the development of trastuzumab (Herceptin) for advanced breast cancer.51 Nevertheless, standardization is a difficult issue because numerous factors may influence the consistency and reliability of immunostaining results, including fixatives, fixation time, AR, antibody clones, detection system, and interpretation (see Part II). In cytopathology, the situation is even worse due to its variable cell sample preparation techniques. Cytopreparation is. .. the foundation of cytomorphology. 52 We believe it is also the foundation of ICC. Therefore, standardization of ICC needs to start with uniform and reliable cytopreparation. 

Umemura, S., Sekido, Y., Itoh, H., and Osamura, RY. 2002. Pathological evaluation of HER2 overexpression for the treatment of metastatic breast cancers by humanized anti-HER2 monoclonal antibody (trastuzumab). Acta Histochemica et Cytochemica, Kyoto 35(2), 77-81. 

Trastuzumab in combination with adjuvant chemotherapy is indicated in patients with early stage, HER2-positive breast cancer. The risk of recurrence was reduced up to 50% in clinical trials. 

Goldenberg, M.M., "Trastuzumab, a Recombinant DNA Derived Monoclonal Antibody, a Novel Agent for the Treatment of Metastatic Breast Cancer," Clin. Ther., 21, 309-318 (1999). 

Herceptin Trastuzumab Genentech, South San Francisco, GA Anti-HER2 Breast cancer 1998... 

Trastuzumab Herceptin Humanized IgGltc anti-HER2 HER2 overexpressing metastatic breast cancer 1998 United States... 

Trastuzumab is licensed for the treatment of early breast cancer that overexpresses human epidermal growth factor receptor-2 (HER2). It may be administered as monotherapy or in combination with, for example, paclitaxel, docetaxel (taxanes) or anastrozole (aromatase inhibitors). Since trastuzumab can cause cardiotoxicity, concomitant use with anthracyclines such as... 

Modi S, Stopeck AT, Gordon MS, Mendelson D, SoUt DB, BagateU R, Ma W, Wheler J, Rosen N, Norton L, Cropp GF, Johnson RG Hannah AL, Hudis CA. (2007) Combination of trastuzumab and tanespimycin (17-AAG KOS-953) is safe and active in trastuzumab-refractory HER-2 overexpressing breast cancer A phase I dose-escalation study. J Clin Oncol 25 5410-5417. 

Trastuzumab Herceptin Genentech-Roche Metastatic breast cancer... 

Trastuzumab Metastatic breast cancer, non-small-cell lung cancer. 

Baselga, J., D. Tripathy, J. Mendelsohn, S. Baughman, C. C. Benz, L. Dantis, N. T. Sklarin, A. D. Seidman, C. A. Hudis, J. Moore, P. P. Rosen, T. Twaddell, I. C. Henderson, and L. Norton. Phase II study of weekly intravenous trastuzumab (Herceptin) in patients with HER2/neu-overexpressing metastatic breast cancer. Semin Oncol. 26 78-83.1999. 

Phase I evaluation of CP-724714 in cancer patients is ongoing [68]. The majority of patients in this trial have breast cancer and have received trastuzumab previously. The MTD was determined to be 250 mg with the dose-hmiting toxicity defined as hyperbilirubinemia and elevated liver enzymes. No objective responses have been reported for the 20 patients evaluated to date. Thirty-five percent of patients have experienced stable disease for an imdetermined period of time. In contrast to trastuzumab, cardiomyopathy has not been observed in this trial. 

Lapatinib is currently undergoing clinical evaluation for several cancer indications. In a phase II study, doses of lapatinib escalating from 1250 to 1500mg/day resulted in ca. 10% objective response in trastuzumab-refractory metastatic breast cancers [71]. More recently, approximately 30% objective response was observed when lapatinib was administered at 1500 mg/qd or 500 mg/bid in first-line ErbB2-positive (as determined by the FISH technique) breast cancer [72]. 

---