Benefit seen in COX-2 expressing tumors, follow-up needed before application to patient care
Regular use of aspirin after colorectal cancer diagnosis may reduce
the risk of cancer death, report investigators from Dana-Farber Cancer
Institute, Massachusetts General Hospital (MGH), and Brigham and Women's
In the August 12 issue of the Journal of the American Medical Association,
the study's authors also find that the aspirin-associated survival
advantage was seen primarily in patients with tumors expressing the
COX-2 enzyme, a characteristic of two-thirds of colorectal cancers.
"While previous studies by our group and others showed that aspirin
and other non-steroidal anti-inflammatory drugs reduce the risk of
developing colorectal cancer, this study is among the first to show that
aspirin can also improve survival in patients who have already been
diagnosed with colorectal cancers. Moreover, the benefit appeared to be
especially strong among patients with cancers that express COX-2," says
Andrew Chan, MD, MPH, of the MGH Gastrointestinal Unit, the study's lead
"This is an important first step toward developing targeted approaches to improving patient outcomes."
Many previous studies have shown that regular use of aspirin and
other non-steroidal anti-inflammatory drugs reduces the risk of
developing colorectal cancer. In 2007, the same MGH/DFCI research team
found that the benefit only applied to tumors overexpressing COX-2, an
enzyme believed to drive tumor growth and known to be inhibited by
aspirin and related drugs.
To test their hypotheses that aspirin would also improve the survival
of patients diagnosed with colorectal cancer, again through its
inhibition of COX-2, the researchers compiled data from two ongoing
prospective research studies — the Nurses Health Study (NHS) and the
Health Professionals Follow-Up Study (HPFS).
Both studies gather comprehensive health information on their
participants every two years; data are then analyzed for associations
between factors such as medication use and the incidence of several
Charles Fuchs, MD, MPH
The current study focused on 1,279 study participants who were
diagnosed with stage 1, 2 or 3 colorectal cancer during their
participation in the studies for whom data was available on aspirin use
before and after diagnosis. Tumor samples available from 459
participants were analyzed for the expression of COX-2.
Study results indicated that patients who regularly took aspirin
after their diagnosis had a nearly 30 percent lower risk of dying of
colorectal cancer during an average of 11 years after diagnosis than did
non-aspirin users. The benefit was especially strong among patients who
began using aspirin after diagnosis.
In contrast, patients who were aspirin users before diagnosis did not
appear to benefit as much from continuing aspirin use after diagnosis.
As expected, the survival benefit appeared restricted to patients with
"We believe our results could lead to improvements in the therapy of
patient with colon cancer," says Charles Fuchs, MD, MPH, of Dana-Farber,
the study's senior author.
"We're now following up this observational study with a randomized
trial to evaluate adding the COX-2 inhibitor celecoxib — which is less
likely to have the gastrointestinal side effects of aspirin — to
Fuchs is an associate professor of Medicine at Harvard Medical
School, where Chan is an assistant professor of Medicine. Study
co-author Shuji Ogino, MD, PhD, is an HMS associate professor of
Pathology at Dana-Farber and Brigham and Women's Hospital. The study was
supported by grants from the National Cancer Institute and the Damon
Runyon Cancer Research Foundation.
Dana-Farber Cancer Institute (www.dana-farber.org)
is a principal teaching affiliate of the Harvard Medical School and is
among the leading cancer research and care centers in the United States.
It is a founding member of the Dana-Farber/Harvard Cancer Center
(DF/HCC), a designated comprehensive cancer center by the National
Massachusetts General Hospital (www.massgeneral.org),
established in 1811, is the original and largest teaching hospital of
Harvard Medical School. The MGH conducts the largest hospital-based
research program in the United States, with an annual research budget of
more than $500 million and major research centers in AIDS,
cardiovascular research, cancer, computational and integrative biology,
cutaneous biology, human genetics, medical imaging and photomedicine.