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. 2011:2011:730360.
doi: 10.1155/2011/730360. Epub 2011 Sep 25.

Role of HER2-Targeted Agents in Adjuvant Treatment for Breast Cancer

Toru Mukohara  1
Affiliations

Role of HER2-Targeted Agents in Adjuvant Treatment for Breast Cancer

Toru Mukohara. Chemother Res Pract. 2011.

Abstract

Approximately 20% of breast cancers overexpress human epidermal growth factor receptor 2 (HER2) protein, mainly as a result of gene amplification. The receptor tyrosine kinase is believed to play a critical role in the pathogenesis and further proliferation of these tumors. The application of trastuzumab, a humanized monoclonal antibody against the extracellular domain of HER2 protein, to HER2-positive metastatic breast cancer has significantly improved treatment outcomes. Following this success, several phase III trials have evaluated the role of trastuzumab in the adjuvant setting, with the result that trastuzumab use is now the standard of care for most HER2-positive early breast cancer patients. In this paper, we review these pivotal phase III trials. We also discuss unresolved issues in adjuvant treatment with trastuzumab, including target patient population, sequential or concurrent use with chemotherapy or radiation, treatment duration, cardiotoxicity, and the possibility of eliminating chemotherapy. Following confirmation of its ability to partially overcome trastuzumab resistance, we also discuss the role of lapatinib in adjuvant use.

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Figures

Figure 1
Figure 1
Schema of treatment regimens and associated cardiotoxicity in the large adjuvant trastuzumab trials. AC, doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2, q3w; PTX, paclitaxel 175 mg/m2, q3w (NSABP B-31) or 80 mg/m2, qw (NCCTG N9831); HER, trastuzumab loading dose of 4 mg/kg followed by 2 mg/kg, qw (NSABP B-31, NCCTG N9831, and FinHER and in combination with DTX in BCIRG 06) or loading dose of 8 mg/kg followed by 6 mg/kg, q3w (HERA and PACS 04 and at trastuzumab alone phase in BCIRG 006); CTx, adjuvant and/or neoadjuvant chemotherapy; RT, adjuvant radiation therapy; DTX, docetaxel 100 mg/m2, q3w; TCH, docetaxel 75 mg/m2 and carboplatin area under the curve (AUC) 6, q3w and trastuzumab loading dose of 4 mg/kg followed by 2 mg/kg, qw; VNR, vinorelbine, 25 mg/m2, qw; FEC, fluorouracil 600 mg/m2, epirubicin 60 mg/m2, and cyclophosphamide 600 mg/m2, q3w (FinHER) or fluorouracil 500 mg/m2, epirubicin 100 mg/m2, and cyclophosphamide 500 mg/m2, q3w (PACS 04); ED, epirubicin 75 mg/m2 and docetaxel 75 mg/m2, q3w; CHF, congestive heart failure; NR, not reported.
Figure 2
Figure 2
Schema of the ALTTO trial; DC, docetaxel and carboplatin.
See this image and copyright information in PMC

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