Cancer Research News
Researchers Find Two Biomarkers with Potential to Predict Breast Cancer Spread
PHILADELPHIA (December 15, 2006) − Expression of two different
proteins taken from primary tumor biopsies is highly associated with
spread of breast cancer to nearby lymph nodes, according to researchers
who say this protein profile could help identify at an early stage those
patients whose disease is likely to metastasize.
In the December 15 issue of Cancer Research, the researchers say
over-expression of one unidentified protein and under-expression of
another is 88 percent accurate in identifying breast cancer that has
spread in a group of 65 patients, compared to an analysis of lymph nodes
If the predictive and diagnostic power of these proteins is validated,
they could be analyzed in primary tumor biopsies that are routinely
collected at the time of diagnosis, saving some women from extensive and
possibly unnecessary treatment as well as from undergoing a second
surgery to collect lymph nodes for analysis, the researchers say.
“We want to be able to predict, at the earliest stages, if a tumor has
spread and how dangerous it will be,” said the study’s lead author, Dave
S. B. Hoon, Ph.D., director of Molecular Oncology at the John Wayne
Cancer Institute, Saint Johns Health Center, in Santa Monica,
California. “These two proteins may allow us to target aggressive tumors
with more extensive therapy management to some women, while sparing
others from needless treatment.”
“Our approach is not to rely on hunting for lymph nodes during surgery,
which will then only tell you whether the nodes are positive or
negative, but to look at the primary tumor to predict how aggressive the
cancer is at early stages,” Hoon said.
The lymph system collects the fluid that surrounds tissue cells, which
is then processed by nearby draining lymph nodes, so checking these
nodes for the presence of cancer is currently one of the most important
prognostic factors predicting breast cancer survival, he said. “One of
the best predictors of systemic cancer spread is whether the draining
lymph node has any signs of metastasis,” he said.
Biopsy of this “sentinel” node occurs after the tumor has been removed
in an initial surgery, and if metastasis is found there, surgeons
continue to sample “downstream” nodes to check for degree of spread.
While this procedure, called “sentinel node biopsy” is now practiced
routinely in the U.S. and in many other countries, there remains
controversy in the accurate assessment of micrometastasis in sentinel
lymph nodes, according to Hoon. He said recent studies have found that
it can produce both false positive and false negative results.
Furthermore, microdisease seen in the sentinel lymph node doesn’t always
predict that a patient will go on to develop metastatic breast cancer,
said Hoon. “If the primary tumor and nodes are removed in some women,
they will not develop recurrent disease, but in other women, removal of
the nodes may have no impact on the spread of the metastatic disease
that has already occurred prior to surgery.”
In this study, 65 patients with invasive cancer who underwent surgery
and biopsy of the sentinel lymph node and/or other lymph nodes were
enrolled, and investigators were blinded as to the findings of these
lymph node biopsies.
In all, 24 patients (37 percent) were found to have cancer in their
nodes and 41 patients (63 percent) were node negative. To predict lymph
node metastasis, the investigators used a ProteinChip™ to identify
biomarkers that distinguished between the tumor profile with paired
positive and negative nodes.
Two protein peaks associated with lymph node metastasis were identified.
Specifically, over-expression of protein peaks at 4,871 Da (which
represents the molecular weight of the protein) and under-expression of
a protein peak at 8,596 Da were highly predictive of lymph node
Patients with two or more positive lymph nodes were significantly more
likely to show over-production of 4,871 Da, compared to patients with no
lymph node spread. The peak at 4,871 could also predict patients with
four or more metastatic nodes who have significantly worse outcomes.
Although they don’t know what these proteins are, by searching a protein
database Hoon suggests that 4,871 Da may represent thymosin beta-10, a
peptide that has already been associated with out-of-control growth and
cell differentiation, and that 8,596 Da could represent an ubiquitin
protein associated with a good prognosis in node-negative breast cancer.
“Protein peaks found in our study may be useful as prognostic
biomarkers, but we must be cautious until the identities of these
proteins are known and validated in a larger study,” Hoon said.
The study was funded by the California Breast Cancer
Research Program of the University of California, the Avon Foundation,
and the Leslie and Susan Gonda Foundation. Investigators from Saint
John’s Health Center, Joyce Eisenberg Breast Center, in Santa Monica
also contributed to the study.
Source: American Association for Cancer Research