Aspirin Helps Colon Cancer Patients With DNA Defect

Regular use of aspirin may keep colon cancer from killing patients whose tumors contain a specific gene defect, according to a study that shows how modern gene science can guide use of old drugs.

Previous studies have suggested that regular aspirin use may help keep the disease from spreading. The new data, published in the New England Journal of Medicine, identifies a gene variation linked to the protective effect of aspirin.

Cancer researchers have been using gene tests to select patients likely to benefit from new medicines that target mutations driving tumor growth. The study released yesterday from researchers at Harvard Medical School and Dana-Farber Cancer Institute shows the DNA test method can uncover the potential of other drugs to fight cancer.

“The data are very strong,” said Boris Pasche, chief of hematology and oncology at the University of Alabama at Birmingham, who wrote an editorial accompanying the study, in a telephone interview. “It would be a big deal if these numbers are confirmed.”

Researchers examined tumors from 964 previously treated colon cancer patients and found that the protective effect of aspirin was limited to those whose tumors had a gene defect called PIK3CA.

If it holds up, the finding may lead to a gene test that would allow oncologists to recommend aspirin to only those colon cancer patients likely to benefit from it, Pasche said. Colon cancer patients without the gene defect could avoid being exposed to aspirin’s possible side effects including internal bleeding.

Study Data

Just 3 percent of colon cancer patients with the tumor mutation who regularly took aspirin died from the disease within five years of being diagnosed, compared with 26 percent of those with the mutation who didn’t regularly use aspirin, according to the new findings. Patients without the mutation gained no cancer survival benefit from aspirin, according to the results.

Pasche compared aspirin’s benefit in colon cancer patients with the mutation to the effect of the breast cancer drug Herceptin from Roche Holding AG. Herceptin helps extend the lives of about 20 percent of breast cancer patients with a particular gene defect that drives tumor growth.

Unlike the rigorous trials that led to regulatory approval of Herceptin for breast cancer, the link found with aspirin and the colon cancer gene isn’t definitive and must be confirmed in larger studies, Pasche said. The new study contained only 66 patients who took aspirin and had the tumor mutation that predicted the medicine’s benefit.

Earlier Findings

The study builds on a 2009 analysis that looked at 1,279 men and women with colon cancer participating in the Health Professionals Follow-up Study or the Nurses’ Health Study, said Shuji Ogino, a molecular pathological epidemiologist at Harvard Medical School and Dana-Farber Cancer Institute and senior author on the new study. The 2009 finding, published by Ogino and others in the Journal of the American Medical Association, found that colon cancer patients who took aspirin had a 29 percent lower risk of death from the disease.

Following that result, Ogino and his colleagues tried to see whether genetic testing could pluck out a subset of colorectal cancer patients most likely to benefit from aspirin. They obtained genetic data from old tumor samples from 964 colorectal patients in the two epidemiology studies, leading to the finding that aspirin may help only those cancer patients with the PIK3CA mutation.

Roughly 20 percent of colon cancer patients have mutations in the PIK3CA gene, Ogino said.

The difference in aspirin benefit in patients with the mutation “is quite striking” Ogino said. “This is by far the best marker we have found for prediction of response to aspirin.”

Exactly how the aspirin may help colon patients with the growth-promoting gene mutation is not clear. One possible explanation is that the enzyme called cyclooxygenase-2 blocked by aspirin may interfere with growth-promoting signals produced by the mutant PIK3CA gene, Ogino said.

To contact the reporter on this story: Robert Langreth in New York at rlangreth@bloomberg.net

To contact the editor responsible for this story: Reg Gale at rgale5@bloomberg.net

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