Can Low-Dose Aspirin Lower Ovarian Cancer Risk?

Regular users of low-dose aspirin appear to have a reduced risk of developing ovarian cancer, according to a new study.

Regular users of low-dose aspirin appear to have a reduced risk of developing ovarian cancer, according to a new study. There was also an increased risk associated with long-term use of other analgesics at high doses, particularly non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs).

“There is growing evidence to support a role for inflammation in the development of ovarian cancer,” wrote study authors led by Mollie E. Barnard, ScD, of the Harvard T. H. Chan School of Public Health in Boston. Previous studies exploring whether anti-inflammatory agents can influence the risk for ovarian cancer have yielded mixed results, and other prospective studies lacked the power and data to examine the question thoroughly.

In the new study, the researchers used data from the prospective Nurses’ Health Study (NHS) and Nurses’ Health Study II (NHSII); previously, they used the same cohorts to report that recent use of aspirin or NSAIDs was associated with ovarian cancer–specific survival. The new analysis included a total of 205,498 women, and the results were published in JAMA Oncology.

There were 1,054 incident cases of epithelial ovarian cancer across both studies, covering 1,779,572 person-years in the NHS and 1,884,999 person-years in the NHSII. Across the full cohort, there was no association between current aspirin use and risk of ovarian cancer, with a hazard ratio (HR) of 0.99 (95% CI, 0.83–1.19); the same was true across varying years of aspirin use or cumulative average tablets per week.

When separated into low-dose and standard-dose aspirin, however, an association did emerge. Current low-dose aspirin use was associated with a lower ovarian cancer risk compared with non-use, with an HR of 0.77 (95% CI, 0.61–0.96); there was no association with longer duration of use. No such association was seen with standard-dose aspirin use, at an HR of 1.17 (95% CI, 0.92–1.49).

Current use of non-aspirin NSAIDs, meanwhile, was positively associated with the risk of ovarian cancer when compared with non-use, with an HR of 1.19 (95% CI, 1.00–1.41). Compared with no regular use, those who used these agents for 10 years or longer had a higher risk, with an HR of 1.34 (95% CI, 1.06–1.70; P = .02 for trend). No associations between acetaminophen use and ovarian cancer risk were observed.

The authors wrote that mechanisms unique to low-dose aspirin, such as the irreversible inhibition of platelet COX-1, may be driving the associations seen in this study. Though other analgesics share some of aspirin’s mechanisms of action, they do differ in some ways, including the extent to which they block COX-1 and COX-2.

“Further exploration is warranted to evaluate the mechanisms by which heavy use of aspirin, non-aspirin NSAIDs, and acetaminophen may contribute to the development of ovarian cancer risk,” they wrote.

Commenting on the study, Victoria L. Seewaldt, MD, of the City of Hope Comprehensive Cancer Center in Duarte, California, wrote that the study has “the power to start to change clinical practice,” but before that can happen, there are still unanswered questions about aspirin’s role in chemoprevention. “To reach the full promise of aspirin’s ability to prevent cancer, there needs to be better understanding of dose, duration, and mechanism,” she wrote.

The effect of only low-dose aspirin on ovarian cancer suggests the mechanism involved is an anti-platelet effect. “The paradigm that cancer is associated with inflammation and that aspirin prevents cancer by reducing inflammation does not hold,” Seewaldt wrote. “To realize the full potential of aspirin in precision chemoprevention, the molecular underpinnings of these important risk reduction effects also need to be defined.”