MEDICAL DEVICE INNOVATION - Medical Device Daily

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New breast cancer marker may
predict likelihood of spreading
MEDICAL DEVICE INNOVATION 2010
By AMANDA PEDERSEN
Medical Device Daily Staff Writer
If cancer doctors had a crystal ball they could peer into
and know whether or not a particular patient’s cancer will
spread, it would take the guesswork out of choosing which
treatment option is best.
For now, the next-best thing may be the discovery of a
new breast cancer marker associated with metastasis that
may lead to the development of a tissue test to predict the
likelihood of metastasis via the bloodstream.
In a small, case-control study, researchers at NewYork-
Presbyterian Hospital/Weill Cornell Medical Center
(New York) have linked the density of the new marker,
called Tumor Microenvironment of Metastasis (TMEM), with
the development of distant organ metastasis via the bloodstream.
According to the authors, that is the most common
cause of death from breast cancer. They also noted that
about 40% of breast cancer patients relapse and develop
metastatic disease and that roughly 40,000 women die of
metastatic breast cancer every year.
“Currently, anyone with a breast cancer diagnosis fears
the worst – that the cancer will spread and threaten their
lives. A tissue test for metastatic risk could alleviate those
worries, and prevent toxic and costly measures like radiation
and chemotherapy,” says senior author Joan Jones, MD,
professor of clinical pathology and laboratory medicine at
Weill Cornell Medical College and director of Anatomic
Pathology at NewYork-Presbyterian Hospital/Weill Cornell
Medical Center.
In the study, investigators performed a retrospective
analysis of tissue samples from 30 patients with invasive
ductal carcinoma of the breast who developed systemic,
distant-organ metastases. These samples were compared
to matched controls that had breast cancer that did not
spread. The samples were compared by size of the tumor,
differentiation of the tumor (how it looks under a microscope
compared to normal breast tissue), and other factors,
Jones told Medical Device Daily. All patients were female
and underwent primary resection of their breast cancer at
NewYork-Presbyterian Hospital/Weill Cornell Medical
Center between 1992 and 2003.
The researchers found that TMEM density was more
than double in the group of patients who developed systematic
metastases compared with the patients with only
localized breast cancer. Also, they found that in well-differentiated
tumors, where the outcome is generally good, the
TMEM count was low.
“If patients can be better classified as either low risk or
high risk for metastasis, therapies can be custom tailored
to patients, preventing over-treatment or under-treatment
of the disease,” said first author Brian Robinson, MD, resident
in Anatomic Pathology at NewYork-Presbyterian
Hospital/Weill Cornell Medical Center.
The Integrative Cancer Biology Program of the National
Cancer Institute funded the study. Because the analysis was
done on a very select group of patients, Jones said the findings
would have to be validated in a larger sample group
before the test could be rolled out.
“What we need to do next, before we could make this a
more generally applicable test, is we need to do a population
study . . . using a much broader range of subjects,”
Jones said. “So we’re trying to get funding to do that and get
a bunch more people – a few hundred, lets say – so we can
see if what we observed in these select patient samples
[can be made] more general.”
The Weill Cornell investigators set out to build on previous
research by co-author John Condeelis, PhD, of the
Albert Einstein College of Medicine (Bronx, New York).
Working in animal models, he identified a link between
blood-borne or systemic metastasis and a three-part association
between invasive carcinoma cells, perivascular
white blood cells (macrophages) and the endothelial cells
that line vessel walls. To confirm this finding in humans,
Jones and Robinson developed a triple immunostain for
human breast cancer samples that simultaneously labels
the three cell types that together they named TMEM.
“What made us try this in the human samples is what
had been observed in some of the animal models of breast
cancer,” Jones said.
In some of the animal models scientists have been able
to actually look at the tumor in the live animal and watch
cells move in the vessels.
Jones admitted that the fact that this test did seem to
work in the case-control study was somewhat surprising to
her.
“This is a very novel way for a pathologist like me to
look at tissue,” she tells MDD. “It’s not intuitive, it is kind of
a new concept.”
Jones said that before she and her colleagues did the
case-control study, they had analyzed “a bunch of breast
cancers” and stained them and looked for these TMEM
structures and counted them. In those tumors where the
outcome was moderate or poor, the researchers counted a
higher number of the TMEMs. “That encouraged us to think,
‘well maybe this means something,’” she said.
Likewise, in the case-control study, the cancers that
metastasized had a higher number of TMEMs than the cancers
that did not spread. “It did seem to have some reflection
of that tumor’s ability to get into blood vessels,” Jones
said.
Notably, Jones said TMEM density was associated with
the development of distant-organ metastasis, independent
of lymph node status and tumor grade.
“Traditionally, the likelihood of breast cancer metastasis
is estimated based on tumor size, tumor differentiation
– how similar or dissimilar the tumor is compared to nor-
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