Trastuzumab Use in Breast Cancer: Clinical Issues

John Horton, MB, ChB

Disclosures

Cancer Control. 2002;9(6) 

In This Article

Abstract and Introduction

Background: Overexpression of the epidermal growth factor 2 HER2 in breast cancer tissue is associated with shorter survival. Trastuzumab, a monoclonal antibody against HER2, can induce tumor responses when given alone and enhances the effectiveness of several chemotherapeutic agents.
Methods: The recent clinical data on outcomes regarding testing for HER2 overexpression and the tolerance, toxicity, and antitumor effects of trastuzumab are reviewed.
Results: Trastuzumab use is indicated either alone or with chemotherapy only in patients with IHC 3+ or FISH+ test results and survival is prolonged in patients with metastatic disease. Cardiac toxicity differs from anthracycline cardiac toxicity and is often reversible.
Conclusions: The safety and efficacy profile of trastuzumab in patients with metastatic disease has led to large-scale testing of addition of the intervention in the adjuvant setting.

The human epidermal growth factor receptor 2 (HER2), also known as c-erbB-2 and HER2/neu, promotes cell growth and tumor development. HER2 protein overexpression is observed in 25% to 30% of primary breast cancers and is associated with shorter survival.[1]

Trastuzumab is a recombinant DNA-derived humanized monoclonal antibody that selectively binds to the extracellular domain of HER2. In patients with metastatic breast carcinomas that overexpress HER2,trastuzumab produces antitumor responses when used alone.[2,3] When combined with chemotherapy, response rates are increased, and survival is prolonged in comparison with treatment using chemotherapy alone.[4] Trastuzumab was approved for use in the United States in 1998 and is now an integral part of the management of HER2-positive patients with metastatic breast cancer. Clinical studies to determine the role of trastuzumab in the adjuvant therapy of breast cancer patients who are at risk for recur-rence are underway. The drug is generally well tolerated, but cardiac toxicity with trastuzumab has been reported in the range of 4% when the drug is used alone, with higher rates when used with chemotherapy.[4]

The extent of benefit from using the drug in association with chemotherapy in patients with HER2-positive advanced breast cancer is clear-cut. Slamon et al[4] described near doubling of response rates and time to progression when trastuzumab was added to chemotherapy (doxorubicin/cyclophosphamide or paclitaxel). More important, a 5-month longer median overall survival was observed with the drug combination.

Several clinical questions concerning the optimal use of trastuzumab remain unanswered. Unfortunately, not all will be answered by clinical trials, in part because of a relative paucity of patients available who can be entered onto clinical research studies. This review is intended to identify some of the salient areas of controversy or lack of knowledge regarding the clinical use of trastuzumab in patients with breast cancer and to present available data that might assist clinicians in developing a rational approach to optimal clinical care of patients with HER2-overexpressing breast cancer.

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