Trastuzumab in breast cancer

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MEK inhibitor selumetinib (AZD6244, AstraZeneca).94,95 In 2010, BKM120 advanced to a Phase I II trial as a combination therapy with trastuzumab in breast cancer patients. A second compound, BYL719, began a Phase II trial in late 2010 in patients with solid tumors with a mutation of the PIK3CA gene however, the properties and biological activities of this compound have yet to be disclosed. 

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. 

Milano G, Lescaut W, Formento J et al. HER2 genetic polymorphism and pharmacodynamics of trastuzumab-based treatment in breast cancer patients. J Clin Oncol 2005 23 501. 

Bussolati G, Montemurro F, Righi L, et al. A modified Trastuzumab antibody for the immunohistochemical detection of HER-2 overexpression in breast cancer. Br. J. Cancer. 2005 92 1261-1267. 

Many clinicians now prefer to use docetaxel (licensed to be used in combination with trastuzumab for metastatic breast cancer) instead of paclitaxel as it is more convenient to administer (1 hour infusion for docetaxel instead of 3 hours for paclitaxel) and clinicians generally have more experience of using this agent in breast cancer therapy. The pivotal trial of this combination shows superiority of docetaxel and trastuzumab over docetaxel alone in terms of overall survival, response rate and time to disease progression with little additional toxicity (Marty etal., 2005). 

Bems, K. et al. 2007. A functional genetic approach identifies the PI3K pathway as a major determinant of trastuzumab resistance in breast cancer. Cancer Cell 12, 395 402. 

Molina, M. A., Codony-Servat, J., Albanell, J., Rojo, F., Arribas, J., and Baselga, J. (2001). Trastuzumab (herceptin), a humanized anti-Her2 receptor monoclonal antibody, inhibits basal and activated Her2 ectodomain cleavage in breast cancer cells. Cancer Res. 61, 4744-4749. 

Longo R, D Andrea M, Sarmiento R, Gasparini G (2010) Pharmacogenetics in breast cancer focus on hormone therapy, tax-anes, trastuzumab and bevacizumab. Expert Opin Investig Drugs 19(Suppl 1) S41-S50... 

Mass RD, Press MF, Anderson S, et al. Evaluation of clinical outcomes according to HER2 detection by fluorescence in situ hybridization in women with metastatic breast cancer treated with trastuzumab. Clin Breast Cancer. 2005 6 240-246. 

D. Monoclonal Antibodies Rituximab is a monoclonal antibody to a surface protein in non-Hodgkin s lymphoma cells. It is presently used with conventional anticancer drugs (eg, cyclophosphamide plus vincristine plus prednisone) in low grade lymphomas. Trastuzumab is a monoclonal antibody to a surface protein in breast cancers that overexpress the HER2 protein. Acute toxicity of these antibodies includes nausea and vomiting, chills, fevers, and headache. Rituximab use is associated with hypersensitivity reactions and myelosuppression. Trastuzumab may cause cardiac dysfunction, including congestive heart failure. 

Each of the drugs listed has been used in drug regimens for breast cancer, but only trastuzumab has specificity in its actions. The drug is a monoclonal antibody to a surface protein in breast cancer cells that overexpress the HER2 protein. Consequently, trastuzumab has value in a specific subset of breast cancers. The answer is (E). 

Pegram MD, O Callaghan C. Combining the anti-HER2 antibody trastuzumab with taxanes in breast cancer results and trial considerations. Clin Breast Cancer 2001 2(Suppl 1) S15-9. 

Ky B, Putt M, Sawaya H, French B, Januzzi JL, Sebag LA, et al. Early increases in multiple biomarkers predict subsequent cardiotoxicity in breast cancer patients treated with doxorubicin, taxanes, and trastuzumab. J Am Coll Cardiol 2014 63(8) 809-16. 

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