Medline ® Abstract for Reference 134
of 'Adjuvant therapy for resected stage III (node-positive) colon cancer'
Expression of HLA class I antigen, aspirin use, and survival after a diagnosis of colon cancer.
Reimers MS, Bastiaannet E, Langley RE, van Eijk R, van Vlierberghe RL, Lemmens VE, van Herk-Sukel MP, van Wezel T, Fodde R, Kuppen PJ, Morreau H, van de Velde CJ, Liefers GJ
JAMA Intern Med. 2014;174(5):732.
IMPORTANCE: Use of aspirin (which inhibits platelet function) after a colon cancer diagnosis is associated with improved overall survival. Identifying predictive biomarkers of this effect could individualize therapy and decrease toxic effects.
OBJECTIVE: To demonstrate that survival benefit associated with low-dose aspirin use after a diagnosis of colorectal cancer might depend on HLA class I antigen expression.
DESIGN, SETTING, AND PARTICIPANTS: A cohort study with tumor blocks from 999 patients with colon cancer (surgically resected between 2002 and 2008), analyzed for HLA class I antigen and prostaglandin endoperoxide synthase 2 (PTGS2) expression using a tissue microarray. Mutation analysis of PIK3CA was also performed. Data on aspirin use after diagnosis were obtained from a prescription database. Parametric survival models with exponential (Poisson) distribution were used to model the survival.
MAIN OUTCOMES AND MEASURES: Overall survival.
RESULTS: The overall survival benefit associated with aspirin use after a diagnosis of colon cancer had an adjusted rate ratio (RR) of 0.53 (95% CI, 0.38-0.74; P< .001) when tumors expressed HLA class I antigen compared with an RR of 1.03 (0.66-1.61; P = .91) when HLA antigen expression was lost. The benefit of aspirin was similar for tumors with strong PTGS2 expression (0.68; 0.48-0.97; P = .03), weak PTGS2 expression (0.59; 0.38-0.97; P = .02), and wild-type PIK3CA tumors (0.55; 0.40-0.75; P< .001). No association was observed with mutated PIK3CA tumors (0.73; 0.33-1.63; P = .44).
CONCLUSIONS AND RELEVANCE: Contrary to the original hypothesis, aspirin use after colon cancer diagnosis was associated with improved survival if tumors expressed HLA class I antigen. Increased PTGS2 expression or the presence of mutated PIK3CA did not predict benefit from aspirin. HLA class I antigen might serve as a predictive biomarker for adjuvant aspirin therapy in colon cancer.
Department of Surgery, Leiden University Medical Center, Leiden, the Netherlands.