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Senior Citizen Health & Medicine
Ability of Breast Cancer to Spread Detected by Two
Protein Biomarkers
88% accurate in identifying breast cancer spread
in a study group
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.
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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 and outcomes.
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
studys 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 doesnt 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," he said.
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 metastasis.
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 dont 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.
Editor's Notes:
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 Johns Health Center, Joyce Eisenberg Breast Center, in Santa
Monica also contributed to the study.
The mission of the American Association for
Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is
the world's oldest and largest professional organization dedicated to
advancing cancer research. The membership includes more than 24,000
basic, translational, and clinical researchers; health care
professionals; and cancer survivors and advocates in the United States
and more than 70 other countries.
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