Aspirin therapy improves survival in patients whose colon cancers express HLA class 1 antigen, but not in those whose tumors have lost that expression, investigators reported online March 31 in JAMA Internal Medicine.
Researchers analyzed tumor samples from a Netherlands cancer registry, which had been obtained from 999 patients who had undergone resection of colon cancer during a 6-year period and whose medical records included information on prophylactic aspirin use. Approximately 18% of the cohort took low-dose aspirin therapy, Dr. Marlies S. Reimers of Leiden University Medical Center, the Netherlands, and her associates reported.
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During 5-10 years of follow-up, 465 patients died. Overall mortality was 37.9% among aspirin users, significantly lower than the 48.5% rate among nonusers.
During 5-10 years of follow-up, 465 patients died. Overall mortality was 37.9% among aspirin users, significantly lower than the 48.5% rate among nonusers.
A total of 963 tumors could be analyzed for human leukocyte antigen (HLA) class I antigen expression; 66.8% were positive and 33.2% were negative for this expression. Overall survival was significantly longer among aspirin users whose tumors expressed HLA class I antigen, with a relative risk of 0.61. This protective effect remained robust, with an RR of 0.53, after the data were adjusted to account for potential confounders. In contrast, patients whose tumors had lost HLA class I antigen expression showed no survival benefit with aspirin therapy, with an adjusted RR of 1.03.
"Our data would be compatible with the hypothesis that aspirin inhibits platelet–tumor cell signaling (which is dependent on intact HLA antigen expression) and prevents epithelial-mesenchymal transition in circulating tumor cells, thereby reducing the metastatic potential," Dr. Reimers and her associates said (JAMA Intern. Med. 2014 March 31 [doi:10.1001/jamainternmed.2014.511]).
If these findings are confirmed in future studies, tumor expression of HLA class 1 antigen may serve as a predictive biomarker for adjuvant aspirin therapy in patients with colon cancer, they added. "Low-dose daily aspirin may suffice as an antimetastatic therapy in patients with
early-stage cancer," and because circulating tumor cells are found in the perioperative period, "it could be argued that aspirin therapy should be initiated as soon as considered clinically appropriate after diagnosis," they said.
This work was supported by the Sloos-Alandt family. Dr. Reimers reported no potential financial conflicts of interest; her associates reported ties to the PHARMO Institute, which receives partial funding from several pharmaceutical companies, and to the Aspirin Foundation and Bayer.