Regular Aspirin Use After Diagnosis of Colorectal Cancer May Reduce Mortality in Patients with Tumor PIK3CA Mutation
DynaMed Weekly Update - Volume 7, Issue 45
A number of randomized trials and observational studies have investigated the efficacy of regular aspirin use for colorectal cancer prevention. Though results have been mixed, the benefits that have been shown are thought to result from aspirin’s inhibition of cyclooxygenase-2 (COX-2). COX-2 (also known as prostaglandin-endoperoxide synthase 2 [PTGS2]) promotes cell proliferation and inflammation and is overexpressed in many colorectal cancers.
There has been less research on the effects of regular aspirin use after the diagnosis of colorectal cancer. In one cohort study with 1,279 participants from the Nurses’ Health study and Health Professionals Follow-up Study, aspirin use was associated with an overall survival advantage during 12 years of follow-up in patients taking aspirin (JAMA 2009 Aug 12;302(6):649). In a subgroup analyses, this advantage was found in patients with primary tumors that overexpressed COX-2, but not in cases of weak or absent COX-2 expression. A new analysis in the same population now suggests that aspirin may be of most benefit in patients whose cancers have a mutation in the PIK3CA gene, which may upregulate COX-2 activity and inhibit apoptosis in cancer cells.
A total of 964 patients (mean age 68 years, 56% female) with colorectal cancer with known PIK3CA status were followed for median 12.75 years. The PIK3CA mutation was present in 16.7%, while the remainder of patients had wild-type PIK3CA cancers. After cancer diagnosis, 41% with the mutation and 42% without the mutation used aspirin regularly (defined as use during most weeks, regardless of dose or indication).
Comparing regular aspirin use vs. nonuse in patients with the PIK3CA mutation, overall mortality was 27.3% vs. 46.3% (p < 0.05, NNT 6), and cancer-specific mortality was 4.5% vs. 27.4% (p < 0.05, NNT 5) (level 2 [mid-level] evidence). In patients without the mutation, there were no significant differences in overall mortality (40.7% vs. 42.1%) or cancer-specific mortality (19.3% vs. 20.6%). About 43% overall used aspirin regularly prior to diagnosis, but there were no significant associations found between prior use and mortality (N Engl J Med 2012 Oct 25;367(17):1596).