Topics:

HER2 Testing and Correlation With Efficacy of Trastuzumab Therapy

HER2 Testing and Correlation With Efficacy of Trastuzumab Therapy

 

The emerging era of targeted cancer therapies has focused laboratory scientists and clinicians on the need to define and understand molecular targets of novel drugs. For breast cancer patients and doctors, this trend is not news—efforts have been under way for decades to identify the estrogen and progesterone receptors and define the value of these markers as predictors of response to hormonal therapy.

With the characterization of the human epidermal growth factor receptor 2 (HER2) and the development of an anti-HER2 therapy—trastuzumab (Herceptin)—which can improve survival and quality of life in women with HER2-overexpressing metastatic breast cancer, there is again the imperative to use laboratory assays to select breast cancer patients for targeted therapy.[1]

HER2 Evaluation

Fornier and colleagues based at Memorial Sloan-Kettering Cancer Center have written a comprehensive review of current methods of HER2 testing and have also highlighted important clinical trials of trastuzumab. This review comes at an important time. HER2 testing is becoming increasingly routine for tumors in women with both early- and advanced-stage breast cancer.

The need for testing in the setting of advanced disease is apparent—to select patients for possible trastuzumab therapy. The most compelling rationale for testing in early-stage disease is the possibility of offering patients trastuzumab therapy as part of ongoing, national cooperative group randomized trials that will define the role of the drug in this setting. As a predictable consequence of widespread testing, however, there is tremendous controversy as to the optimal way to test tumors for HER2 status.

As Fornier et al describe, there are two widely used strategies for HER2 testing—immunohistochemistry, which measures surface expression of the HER2 protein, and fluorescence in situ hybridization (FISH), which measures the copy number of the HER2 oncogene. Retrospective studies of the natural history of operable breast cancer[2] and randomized trials of chemotherapy with or without trastuzumab[3] suggest that FISH may be a better test for predicting HER2-related outcomes than immunohistochemistry.

These studies, along with others also performed by large centralized laboratories,[4] confirm that most of the difference is due to the confounding presence of "2+" positive tumors identified by immunohistochemistry. Only a small fraction of these immunohistochemistry 2+ cases have HER2 gene amplification and increased HER2 mRNA expression; the vast majority are true false-positives. For this reason, it is standard practice at our institution for all 2+ tumors identified by immunohistochemistry to be tested by FISH.

Pages

 
Loading comments...

By clicking Accept, you agree to become a member of the UBM Medica Community.