Interview
with Neil Love, MD from Breast Cancer Update for Medical Oncologists,
Program 3 2000
Play
Audio Below:
The
history of the development of HER2 testing is interesting, at least
from a clinical trialer’s perspective. We should not loose
sight of the fact that the patients selected for Herceptin clinical
trials were selected on the basis of the "clinical trials assay,"
which involve the use of a monoclonal antibody called CB11 –
which tends to be targeted at the cytoplasmic domain – and
4D5, a mouse homologue of Herceptin which actually targets the extracellular
domain. The immunohistochemical assay that was subsequently approved
by the FDA, the Daco HercepTest, was not the one used in these clinical
trials although in the hands of many pathologists, the Daco HercepTest
has yielded HER2 positivity rates that are much higher than we have
expected historically – often as high as 45or 50%. So, the
questions that are raised in my mind are, "Does the Daco HercepTest
have adequate specificity? Are we necessarily detecting HER2 all
the time or are we detecting other members of the EGF receptor super
family?" And then the other issue that we need to consider
carefully, is whether examining gene amplification by fluorescent
in situ hybridization might be a preferable test.
Clearly
FISH for the present time is more expensive, requires perhaps a
uniquely trained pathologist and pathology technicians to perform
the test but may perhaps more reliable in certain circumstances.
In most pathology labs those tumors that were scored as 0 really
are 0 or, at least, from a decision making perspective to use or
not use Herceptin, one doesn’t need to do any further testing.
Those tumors that test 3+ by immunohistochemistry really are 3+
and even if you aired in your epitope retrieval or your antigen
retrieval technique and it’s a 2+, you are really not going
to do too much harm by giving that patient Herceptin. It’s
the 2+ and 1+ patients that cause us the most confusion, and here
I think it’s entirely reasonable when your patient tests 2+
or 1+ by immunohistochemistry to corroborate the result with FISH
and you can do this on paraffin embedded tissue.
