Tests similar to this identify unique proteins in blood from women with breast cancer. In each of the four 25-dot squares, each dot represents one of 21 different proteins being measured in one blood sample. The color indicates how much of the protein is present. Image: Pacific Northwest National Laboratory |
Early detection of breast cancer saves thousands of lives
each year. But screening for breast cancer also produces false alarms, which
can cause undue stress and costly medical bills. Now, a recent study using
patient blood reveals a possible way to reduce the number of false alarms that
arise during early screening. Researchers found a panel of proteins shed by
breast cancer that are easily detected and can distinguish between real cancer
and benign lumps.
This study used diagnostic tools that are already in use
in clinics. If the results can be replicated with more volunteers and over a
longer period of time, the transition from research laboratory to clinical laboratory
would be straightforward.
“We were surprised to see we could distinguish
between accurate and false results produced by cancer screens such as
mammograms,” says Department of Energy’s Pacific Northwest National
Laboratory biologist Richard Zangar, who led the study published in Cancer Epidemiology, Biomarkers &
Prevention. “We really want to expand the work to verify our
findings.”
Finding breast cancer is the first step to treating it,
but mammograms have a high rate of false alarms. Many women go through
unneeded, invasive follow-up tests. To improve the process, some researchers
are working on a simple clinical blood test that would detect proteins shed by
cancerous tissues.
Called biomarkers, these proteins aren’t doing much
better than mammograms when it comes to false positives in experimental
studies. But researchers have been approaching biomarkers as if every type of
breast cancer is the same. In reality, breast cancer exists as several
subtypes, with each subtype having distinct characteristics.
For example, breast cancers that produce proteins called
estrogen receptors are a different subtype from ones that don’t and respond to
different therapies. Zangar and colleagues wondered if looking for biomarkers
specific for different subtypes would improve the odds of getting the diagnosis
right.
To explore this idea, Zangar and his colleagues at PNNL
and Duke University picked 23 candidate
biomarkers and measured them using tests similar to the ones found in
clinics. The team compared proteins in blood from four groups of women—about
20 women in each of the four subtypes of breast cancer—to women with benign
lumps that had previously been identified as false positives. Then, Zangar’s
team homed in on a handful of biomarkers for each subtype that could best
distinguish between the most true positives and the least false positives.
The biomarker panel for each subtype was significantly
better at distinguishing between breast cancer and benign lumps than mammograms
or single biomarkers. The statistical test the team used rates performance from
0.5 to 1.0—with 0.5 indicating the biomarker panel predicts cancer randomly and
1.0 means it’s perfect. Mammograms and the best single biomarkers rank around
0.8. But for two of the most common breast cancer subtypes, the biomarker
panels ranked above 0.95 and reached 0.99 depending on which proteins were
included in the panel.
“Perhaps researchers haven’t found good biomarkers
because they’ve been treating the different subtypes as a single disease, but
they actually represent unique diseases that are associated with different
biomarkers,” says Zangar. “We’re hopeful these results can be
repeated because these assays would markedly improve our ability to detect
breast cancer early on, when treatment is more effective, less costly, and less
harsh.”
In addition, the study hints about the underlying biology
of breast cancer. Four of the biomarkers are proteins involved in normal breast
development that turn on and off at different times during growth. The fact
that these proteins show up in different ways, depending on the subtype of breast
cancer, might provide clues about what goes wrong when breast tissue turns
cancerous.
The team is seeking additional funding to repeat the
study in larger groups of women and to follow volunteers for several years.
