COPENHAGEN, Denmark--Dako Corporations HercepTest was
recommended unanimously for FDA approval by a joint committee of the
Hematology and Pathology Devices Panel and Immunology Devices Panel,
conditional on the company providing clear guidelines on how to
conduct the test, so that laboratories can provide consistent results.
The new immunohistochemical test was designed specifically to
identify patients with breast cancer whose tumor tissue overexpresses
the HER2 protein. It is a result of an agreement announced last March
in which Genentech, maker of Herceptin (trastuzumab), granted Dako a
license, under its patent rights, to develop the test. A positive
HercepTest result will aid in the assessment of patients with
metastatic breast cancer for whom treatment with Herceptin is being
considered. The Oncologic Drugs Advisory Committee (ODAC) has
recommended that Herceptin receive FDA approval .
During the Herceptin clinical trials, it was determined that a
simpler test was needed to identify patients who potentially could
benefit from the agent. Dako proposed to the FDA to develop a test
that, if successful, would reach or exceed a concordance level of 75%
when compared to the immunohistochemical assay applied in the
clinical trials for Herceptin. HercepTest exceeded its goal with a
concordance of 79% that was shown to be reproducible in and between labs.
The test is based on a polyclonal antibody developed by Dako for
specific detection of the HER2 protein. The antibody is applied to
the tissue, and its binding is visualized to indicate the level of
antigen in the tissue (figure). [An
available HER2 test kit, Oncor Inc.s Inform, counts copies of
the HER2 gene, rather than measuring the protein level.]
The Dako test is easy to conduct, since it requires relatively few
steps and uses equipment routinely found in pathology laboratories.
It requires about 3 hours to stain specimens of paraffin-embedded
tissue, which is then evaluated by the pathologist against a
predetermined scoring system. (In the figure, the top two sample
stains are rated negative and the bottom two are rated positive).