Trastuzumab therapy

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

Controversy exists as to the most useful assay for HER2-overexpres-sion, particularly for identification of candidates for trastuzumab therapy. Following the approval of trastuzumab, an IHC-based assay (Herceptest), similar but not identical to the trastuzumab clinical trials assay, was developed for this use. Fluorescence in situ hybridization (FISH)-based assays have also been developed to determine HER2 gene amplification. The concordance of these assays with each other and with the trastuzumab clinical trials assay has been questioned (252). Since the probability of response to trastuzumab therapy appears to correlate with the level of HER2 overexpression, further studies will be required to establish standardized HER2 testing procedures. 

Cardiotoxicity Heart failure has been observed in patients receiving trastuzumab therapy alone or in combination with paclitaxel or docetaxel,... 

Routine use of CA 15-3 or CA 27.29 alone not recommended Increasing CA 15-3 or, CA 27.29 may be used to suggest treatment failure. Routine use of CEA not recommended. ER and PR determined for primary lesions. Steroid hormone receptors to be used to sdect patients for endocrine therapy. HER-2/neu (c-ErbB-2) pverexpression or amplification may be used, to select patients for Herceptin (trastuzumab) therapy None. ... 

Tubbs RR, Pettay JD, Roche PC, et al. Discrepancies in clinical laboratory testing of eligibility for trastuzumab therapy Apparent immunohistochemical false-positives do not get the message. J Clin Oncol. 2001 19 2714-2721. 

Chorn N. Accurate identification of H R2-positive patients is essential for superior outcomes with trastuzumab therapy. Oncol Nurs Forum. 2006 33 265-272. 

Another case of already practical use of pharmacogenetic methods is the test for mutations in tumors that overexpress the human EGFR, HER2. Trastuzumab, a humanized monoclonal antibody, is effective in only 10-15% of breast cancer patients whose tumors overexpress HER2 [67]. Therefore, the pretreatment detection of HER2 is essential for the trastuzumab therapy. 

Cardiotoxicity is increased by anthracycline-containing regimens [170 ]. Severe heart failure complicated by left ventricular thrombosis during sequential anthracycline and trastuzumab therapy for breast cancer has been reported after the fifth cycle of trastuzumab [171 ]. 

Onitilo AA, Engel JM, Stankowski RV (2014) Cardiovascular toxicity associated with adjuvant trastuzumab therapy prevalence, patient characteristics, and risk factors. Ther Adv Drug Saf 5 154-166... 

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