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Nurses’ Health Study finds help for colorectal cancer

Thursday October 25, 2012
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Aspirin therapy can extend the life of colorectal cancer patients whose tumors carry a mutation in a key gene, but has no effect on patients who lack the mutation, according to data from the Nurses’ Health Study and Health Professionals Follow-up Study.

Researchers studied more than 900 patients with colorectal cancer, and found that for patients whose tumors harbored a mutation in the PIK3CA gene, aspirin use produced a sharp jump in survival. Five years after diagnosis, 97% of those taking aspirin were still alive, compared with 74% of those not using aspirin.

In contrast, aspirin had no impact on five-year survival rates among patients without a PIK3CA mutation.

"Our results suggest that aspirin can be particularly effective in prolonging survival among patients whose colorectal cancer tests positive for a mutation in PIK3CA," Shuji Ogino, MD, PhD, of Dana-Farber Cancer Institute, Brigham and Women’s Hospital and the Harvard School of Public Health, said in a news release.

"For the first time, we have a genetic marker that can help doctors determine which colorectal cancers are likely to respond to a particular therapy." Ogino cautioned that the results need to be replicated by other researchers before they can be considered definitive.

Although aspirin often is prescribed for colorectal cancer patients, physicians have not been able to predict which patients actually will benefit from the treatment. The new finding suggests that the survival benefit is limited to the 20% whose tumors have the PIK3CA mutation.

For the remaining patients, aspirin still may be used, but it is likely to be much less effective and can lead to gastrointestinal ulcers and stomach bleeding, the researchers noted.

The study was prompted by previous research that suggested aspirin blocks an enzyme called PTGS2 (cyclooxygenase-2), causing a slowdown in the signaling activity of another enzyme, PI3K. That led researchers to hypothesize that aspirin could be especially effective against colorectal cancers in which the PIK3CA gene — which provides a subunit of PI3K — is mutated.

To conduct the study, investigators obtained data on 964 patients with rectal or colon cancer from the Nurses’ Health Study and the Health Professionals Follow-up Study. The data included information on the patients’ use of aspirin after diagnosis and the presence or absence of PIK3CA mutations in their tumor tissue.

The study, which combines the study of disease-related genes and research into large populations of individuals, represents a new, hybrid field that Ogino has termed molecular pathology epidemiology. "The field may help us bring together information from two frontiers of cancer research — at both the molecular and population levels — in ways that are beneficial to patients," he said.

The study appears in the Oct. 25 issue of the New England Journal of Medicine. The study abstract is available at www.nejm.org/doi/full/10.1056/NEJMoa1207756?query=featured_home.


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