AMSTERDAM – Low-dose aspirin was associated with a survival benefit only in colon cancer patients whose tumors expressed human leukocyte antigen class I in an analysis of 999 colon cancers.
"HLA class I might serve as a predictive biomarker to help identify patients who could benefit from aspirin therapy after diagnosis," Dr. Marlies Reimers reported at the multidisciplinary European cancer congresses.
Several studies, including most recently the Women’s Health Study, have reported that regular low-dose aspirin use can help lower the risk of colorectal cancer, particularly hereditary cases, and reduce polyp formation. Aspirin use after diagnosis has also been associated with better survival. The current findings may explain aspirin’s role in this second pathway, Dr. Reimers said.
In an attempt to elucidate the biologic mechanisms behind aspirin’s benefit, the investigators used tissue microarrays to evaluate the expression of HLA class I and cyclooxygenase (COX)-2 in 999 colon cancers and extracted DNA from 663 tumors to study PIK3CA mutations. The patients were registered with the Eindhoven Cancer Registry between 1998 and 2007, and their aspirin use was obtained from a community pharmacy database.
COX-2 is expressed by about 70% of all colon cancers and is related to tumor genesis, as are PIK3CA mutations. HLA class I is produced by the HLA gene family, which is involved in the immune response.
The investigators hypothesized that aspirin’s role in improved survival could be explained by the interaction of platelets with HLA-positive tumor cells circulating in the bloodstream. Platelets are thought to shield tumor cells in the blood so they can’t be recognized by the immune system, promoting their metastatic potential.
Because aspirin attacks platelet formation, "the protective shield will be lost and the tumor cells could be eliminated by the innate immune system," said Dr. Reimers, who is a PhD student in the department of surgery, Leiden (the Netherlands) University Medical Center.
During the 4-year follow-up, aspirin use after diagnosis was associated with a significantly better overall survival (hazard ratio, 0.64; P = .001).
In patients whose tumors expressed HLA class I, aspirin use cut the risk of death in half, Dr. Reimers said at a press briefing.
No protective effect of aspirin was seen in patients whose tumors did not express HLA class I, expressed COX-2, or contained PIK3CA mutations. A possible explanation for finding no association between COX-2 and PIK3CA with survival could be that pharmacologic data on aspirin indicate that systemic concentrations of aspirin, reached with low-dose aspirin, are inadequate to permanently acetylate COX-2, but are optimal for platelet inhibition, she said in an interview.
Dr. Reimers cautioned reporters that the results are not sufficient to suggest that all colorectal cancer patients should begin taking aspirin and that additional evidence from larger trials is needed to support their findings. Two phase III trials are currently underway: the ASCOLT study of aspirin use in Asian patients with Dukes’ C or high-risk Dukes’ B colorectal cancer and the Add Aspirin trial in the United Kingdom.
Dr. Peter Naredi, president of the European Society of Surgical Oncology, commented in a statement that the results are interesting and that ongoing placebo-controlled randomized trials evaluating the effect of aspirin in colorectal cancer can hopefully strengthen the evidence that aspirin is useful in patients with HLA class I expression."
Dr. Reimers reported having no relevant financial disclosures.