Daily aspirin use reduced ovarian cancer risk by 20%

Diljeet K. Singh, MD, DrPH

Aspirin’s potential benefit in reducing ovarian cancer risk by as much as 20% is exciting, biologically plausible and consistent with findings in other malignancies. However, clinical recommendations will need to wait until we answer remaining questions regarding dose, agent and appropriate candidates for use. Given known potential gastrointestinal bleeding and hemorrhagic stroke risk with aspirin and other NSAID use, dose and dose schedule are important questions to answer. Further understanding of mechanism of action also can help us choose agents to consider for future chemoprevention efforts.

The current challenge in the setting of nonrandomized, prospective data is defining groups in whom aspirin could be reasonably recommended. Although we lack the data to recommend the intervention in average- or low-risk women, individuals at higher risk and their providers might contemplate this as an option. Very high-risk groups — such as the BRCA mutation carriers, who have a 10% to 40% chance of getting ovarian and fallopian tube cancers, and Lynch syndrome carriers, who have a 10% to 12% risk — may want to consider prevention while they are in their child-bearing years. Currently, oral contraceptives — which may confer a 30% to 40% decrease in risk — are discussed and often recommended. However, we wouldn’t recommend aspirin for long-term prevention for those groups because the risk of ovarian and fallopian tube cancer is high, screening tools are ineffective and curability is not guaranteed, so we still recommend that these women have their ovaries and fallopian tubes removed after they’ve completed child bearing.

The study authors also raise interesting questions about the mechanisms of the preventive benefits of aspirin and whether COX-1 or COX-2 pathways are at work. On the basis of their findings, the authors purport the specific COX-1 activity of aspirin led to the reduction in risk. COX- 2 inhibitors rofecoxib (Vioxx, Merck) and celecoxib (Celebrex, Pfizer) also have shown promise for prevention of colonic polyps in average- and high-risk patients; however, these trials also showed substantial increase in the risk of myocardial infarction. Indeed, all the NSAIDs have potential significant gastrointestinal and cardiovascular risks.

Given literature supporting possible benefits with both COX-1 and COX-2 inhibitors, perhaps we should consider evaluating anti-inflammatory pathways more broadly. In the context of the current literature, we should continue to study additional sources of COX inhibitors such as curcumin, which is derived from turmeric and has shown potential as a colon cancer preventive agent and is thought to function as a COX-2 inhibitor. Current studies show only gastrointestinal distress at extremely high dose, but additional study is needed if long-term use is being considered. Although curcumin is from a natural source, we may uncover risks when we move from edible quantities of a spice to pharmacologic concentrations and doses. Aspirin also has a natural source, but obviously large doses of aspirin can be life threatening.

Overall, these data suggest that in highly selected patients at high risk for ovarian cancer during childbearing years, we may consider aspirin potentially in combination with other agents such as oral contraceptives. Ultimately, physicians and their patients will need to jointly make clinical decisions, weighing an individual’s risk factors for ovarian cancer — such as genetic mutation status, family history, having an affected first-degree relative, nulliparity, obesity, etc — against the potential risks of use. For all others, additional research is needed.