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Markers
for inflammation discovered in Breast Cancer
Survivors are linked to survival
Newswise — A study led by researchers at
Fred Hutchinson Cancer Research Center has
identified two proteins in the blood that
could become important prognostic markers
for long-term survival in breast cancer
patients.
The
proteins are associated with chronic
inflammation, which is known to contribute
to cancer development and progression.
Cornelia Ulrich, Ph.D., and colleagues
measured the levels of C-reactive protein
(CRP) and serum amyloid A (SAA) in 734
breast cancer patients at 31 months after
diagnosis.
They found that elevated levels of CRP and
SAA are associated with reduced overall
survival, regardless of patient age, tumor
stage, race and body mass index.
For example, women with breast cancer who
had SAA levels that were in the highest
third in amount measured in their blood were
three times more likely to die from their
disease within the following seven years
compared to patients with the lowest-third
amount. Similarly, women in the highest
third of CRP levels had a two-fold increased
risk of death.
“These associations are strong and they
suggest that, in the long-term, elevated
levels of inflammatory markers predict a
woman’s chances of surviving after breast
cancer,” said Ulrich, a member in the
Hutchinson Center’s Cancer Prevention
Program.
“It also appears that there may be a
threshold effect in that only women in the
highest third of inflammation markers had
increased mortality.”
“To our knowledge, this is the largest
population-based cohort study to date that
examined the relationship between systemic
inflammation and breast cancer survival, and
the first to evaluate SAA as a prognostic
marker for breast cancer,” said Ulrich.
CRP and SAA are nonspecific, acute-phase
hepatic proteins that are secreted into the
circulating blood stream in response to
cytokines including interleukin-1,
interleukin-6 and tumor necrosis factor.
Patient data was drawn from the Health,
Eating, Activity and Lifestyle (HEAL) study,
a multi-ethnic NIH-funded prospective group
of women diagnosed with stage 0 through
Stage IIIa breast cancer.
In previous studies, elevated CRP was
associated with poor survival in patients
with metastatic prostate cancer as well as
those with gastroesophogeal, colorectal,
inoperable small-cell lung and pancreatic
cancers.
Preoperative levels of SAA have been
associated with survival of patients with
gastric cancer and those with renal cell
carcinoma.
Likewise, clinical and experimental data
suggest that chronic inflammation promotes
mammary tumor development.
Breast cancer patients have elevated
concentrations of CRP before surgery, more
so in women with advanced disease, which
suggests that CRP may be related to tumor
burden or progression.
Cancer survivors with chronic inflammation
may have an elevated risk of recurrence as a
result of the effects of inflammatory
processes on cell growth or the presence of
cancer cells that induce inflammation,
according to the study.
“It is interesting that markers measured in
the blood nearly three years after diagnosis
predicted prognosis,” Ulrich said.
“We also found these associations to hold up
after adjusting for a number of factors that
associate with systemic inflammation, such
as obesity.
"However,
more research is needed to confirm these
findings and to get more precise estimates
of risk. We also need to learn more about
the biologic mechanisms.”
Ulrich was joined in this study by
researchers from the University of
Washington, the National Cancer Institute,
City of Hope National Medical Center,
University of Southern California and the
University of Louisville.
Funding for the study was provided by the
National Cancer Institute, National
Institutes of Health, National Institute of
Child Health and Human Development,
University of New Mexico, University of
Chicago and the California Department of
Health.
At Fred Hutchinson Cancer Research Center,
our interdisciplinary teams of
world-renowned scientists and humanitarians
work together to prevent, diagnose and treat
cancer, HIV/AIDS and other diseases.
Our researchers, including three Nobel
laureates, bring a relentless pursuit and
passion for health, knowledge and hope to
their work and to the world. For more
information, please visit
fhcrc.org.
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