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Daily aspirin may reduce ovarian cancer risk, extend survival
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The use of aspirin daily may reduce ovarian cancer risk as well as improve survival after diagnosis, according to two separate studies.
Shelley S. Tworoger, PhD, associate center director for population science at Moffitt Cancer Center, and colleagues conducted the studies to help increase understanding of the potential role of inflammation in ovarian cancer development and progression.
The Ovarian Cancer Cohort Consortium (OC3) study — published in Journal of the National Cancer Institute — pooled results of 12 case-control studies that included 758,829 women, of whom 3,514 women developed ovarian cancer.
Results showed reduced ovarian cancer risk among women who used aspirin daily or almost daily compared with women who used it infrequently or not at all (rate ratio [RR] = 0.9; 95% CI, 0.82-1). Researchers observed no such reduction for less-than-daily aspirin use or for NSAIDs, and daily acetaminophen use appeared to slightly elevate ovarian cancer risk.
A second study — published in The Lancet Oncology — focused on 1,143 women with epithelial ovarian cancer included in the Nurses’ Health Study and Nurses’ Health Study II. Women who used daily aspirin after diagnosis achieved longer ovarian-cancer specific survival (RR = 0.68; 95% CI, 0.52-0.89). Researchers observed a similar trend for postdiagnosis use of NSAIDs (RR = 0.67; 95% CI, 0.51-0.87).
HemOnc Today spoke with Tworoger about the role of inflammation in ovarian cancer, the potential use of daily aspirin as a way a preventive measure and a strategy to improve survival, and what must be confirmed in future studies.
Question: Can you elaborate on how a spirin can reduce ovarian cancer risk and improve ovarian cancer survival?
Answer: There is increasing evidence that ovarian cancer is an inflammation-related disease to some extent. This is largely driven by a number of studies that showed women with high C-reactive protein had an increased risk for ovarian cancer. Other studies looked at inflammatory factors, such as aspirin and NSAIDs. However, many of these studies were limited by small sample size. A couple years ago, we built a collaboration with a number of investigators around the world called the Ovarian Cancer Association Consortium. Many of those investigators were asking about aspirin, nonaspirin NSAID and acetaminophen use in their cohort studies. When those studies were pooled, there were a large number of ovarian cancer cases. The results were similar to what has been seen in case-control and retrospective studies, with about a 10% reduction in risk of ovarian cancer with daily aspirin use. There was no such association for non-aspirin NSAID use.
Most patients with ovarian cancer have high morbidity and poor outcomes. There has been very little research into lifestyle changes and factors, or even over-the-counter solutions, that individual patients might be able to use to improve survival. We were able to leverage unique data from the Nurses’ Health Studies, which — among other things — asked women about their aspirin and NSAID use every 2 years, as well as whether they had been diagnosed with ovarian cancer. We confirmed diagnoses with medical records. This allowed us to look at prediagnosis and postdiagnosis aspirin use as it pertained to survival. Women who used aspirin after diagnosis had a 30% lower HR for ovarian cancer-specific mortality. This is a very strong association. However, it was an observational study, not a randomized controlled trial. There are potential biologic pathways to explain this, including reduced inflammation, but also an effect on thrombosis and platelets.
Q: What are the next steps in research? Will you look at strategies to reduce risk and improve survival jointly or separately?
A : Because ovarian cancer is a relatively rare form of cancer, a randomized controlled trial investigating aspirin is unlikely. Even research that has combined data from randomized studies of aspirin use for other diseases did not include enough women with gynecologic cancer to be sufficiently powered. Thus, we have to further explore observational studies. One of the limitations of the current OC3 analysis is that we did not have much information about dosing of aspirin. We are working to pull together that data to determine what dose — low or standard — may be best. We also are trying to look at the molecular mechanisms by which aspirin could be affecting ovarian cancer development. Specifically, we are looking at immune or inflammatory characteristics of the tumors women get.
For the survival data, we are working to replicate this analysis in a subset of cohort studies that have updated questionnaire data. We are using observational data, as well as looking at differences in association based on tumor characteristics. For example, tumors that are more sensitive to aspirin could be more responsive to a daily aspirin intervention. We also are working with colleagues who are conducting animal- and cell-based models to gain further understanding of those processes.
Q: What do you mean by tumors that are more sensitive to aspirin?
A : We don’t yet know what tumors might be more sensitive to aspirin in ovarian cancer. But in colorectal cancer tumors, we know aspirin blocks the enzymes of the COX 1 or COX 2 pathways. Accordingly, colorectal cancer research suggests that tumors that express these receptors respond well to aspirin, so we are going to take a look at that pathway for ovarian cancer. Another important area of research is in the inflammatory or immune profile of the tumor — not the tumor itself, but the immune microenvironment, including immune macrophages regulated by the inflammatory environment of the host.
Q: Are other groups picking up on this line of research?
A: This research is a group effort that includes investigators from Harvard University, NCI, the University of Hawaii and Huntsman Cancer Institute at The University of Utah, among others. Other groups, including researchers at The University of Virginia, also are looking at aspirin and nonaspirin NSAIDs for African-American women with ovarian cancer. The Ovarian Cancer Association Consortium has published papers on aspirin use with risk and prediagnosis analgesic use with survival.
Q: What is your ultimate hope for these studies?
A: I would hope that identifying patients who would most benefit from these interventions will be possible. We also are thinking about aspirin in combination with other therapies. However, we are still a few years away from making an official recommendation. Because aspirin is such a chemotherapeutic prevention agent for cardiovascular and other diseases, we hope to provide enough compelling evidence that it can be used for ovarian cancer prevention, as well. We would at least like it to be part of a conversation any woman could have with her doctor. – by Rob Volansky
References:
Merritt MA, et al. Lancet Oncol. 2018;doi:10.1016/S1470-2045(18)30373-5.
Trabert B, et al. J Natl Cancer Inst. 2018; doi:10.1093/jnci/djy/100.
For more information:
Shelley S. Tworoger, PhD, can be reached at Moffitt Cancer Center, 12902 USF Magnolia Drive, Tampa, FL 33612; email: shelley.tworoger@moffitt.org.
Disclosure: Tworoger reports no relevant financial disclosures.