A recent study shows that a specific subset of patients with colorectal cancer are most likely to benefit from aspirin therapy (NEJM 2012; 367: 1596-606).
This study used data from two prospective cohort studies, the Nurses’ Health Study (n=121,700) and the Health Professionals Follow-up Study (n=51,500). Among these patients, data was analyzed from 964 in whom there was known information on the presence or absence of the PIK3CA mutation. In total, only 161 of these 964 patients had mutations in PIK3CA; 66 of these took aspirin and 95 did not.
Mutations in PIK3CA affect the gene encoding phosphatidylinositol-4,5-bisphosphonate-3-kinase and occur in 15-20% of colorectal cancers. Up-regulation of this gene enhances prostaglandin E2 synthesis and prostaglandin-endoperoxide synthase 2 (also known as cyclooxygenase-2) which results in the inhibition of apoptosis in colon-cancer cells. Due to this mechanism, the authors hypothesized that blocking this pathway with aspirin would have a beneficial outcome with regard to tumor molecular characteristics and patient outcomes.
Mutations in PIK3CA were detected with PCR and pyrosequencing after DNA extraction from paraffin-embedded tissues.
Among patients with mutated-PIK3CA colorectal cancers, regular use of aspirin after diagnosis was associated with better survival. Hazard ratio for cancer-related death was 0.18 and overall death rate also was lower with hazard ratio of 0.54. In patients without this mutation (wild-type PIK3CA), regular use of aspirin was not associated with a survival advantage; hazard ratio of cancer-specific survival was 0.96 and overall survival hazard ratio was 0.94.
While this study had data on a large number of other characteristics, including BRAF, KRAS, CIMP, LINE-1, and microsatellite instability, it lacked statistical power to examine many of these other modification effects.
These data, if confirmed, indicate a role for aspirin in colorectal cancer patients with PIK3CA mutations.
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