Analysis of data from two ovarian cancer consortia shows that frequent aspirin use was associated with a 13% reduction in ovarian cancer risk. A similar risk reduction was observed for high-grade serous ovarian cancer, the most common and one of the most fatal histological types, which is important because most established risk factors are weakly associated with high-grade serous ovarian cancers. The consistency of the frequent aspirin use and ovarian cancer association across the individual case-control and cohort study populations was notable and provides support for a beneficial effect of frequent aspirin use on ovarian cancer risk. Findings are published by Lauren M. Hurwitz, PhD, MHS of the Division of Cancer Epidemiology and Genetics, National Cancer Institute in Rockville, MD, US and colleagues on 22 July 2022 in the Journal of Clinical Oncology.
The authors wrote in the background that a growing body of evidence supports a role of aspirin in reducing ovarian cancer risk. Pooled secondary analyses of randomised controlled studies of aspirin for cardiovascular disease prevention have noted a decreased risk of female reproductive cancers with at least 3 years of aspirin use. However, too few ovarian cancer cases were diagnosed in these study populations to draw inferences for ovarian cancer specifically. Furthermore, in the observational setting, individual study results have been mixed, but meta-analyses and pooled analyses of cohort and case-control studies have found that aspirin may reduce ovarian cancer risk by 10%-20%, particularly when used frequently (e.g. daily or almost daily).
Although aspirin use appears to be one of the few modifiable protective factors for ovarian cancer, population-wide chemoprevention programmes are generally considered not feasible because of the low incidence of ovarian cancer and the known risk of bleeding conferred by frequent aspirin use. Such programmes will likely need to focus on subgroups of women at elevated risk of ovarian cancer. Whether frequent aspirin use reduces risk of ovarian cancer among subgroups of women defined by these risk factors is unknown, and extremely large, well-powered studies are needed.
In this analysis, the authors leveraged harmonised, individual-level data from two ovarian cancer consortia that previously reported on frequent aspirin use and ovarian cancer risk to comprehensively assess this association across key subgroups of interest. Meta-analysis of results from the 17 studies aimed to test for the consistency of the association across study design and personal characteristics and provide the most precise estimates of the association between aspirin use and ovarian cancer.
In the analysis were included 9 cohort studies from the Ovarian Cancer Cohort Consortium with 2,600 cases and 8 case-control studies from the Ovarian Cancer Association Consortium with 5,726 cases. The authors used Cox regression and logistic regression to assess study-specific associations between frequent aspirin use defined as use of at least 6 days per week and ovarian cancer risk, and combined study-specific estimates using random-effects meta-analysis. They conducted analyses within subgroups defined by individual ovarian cancer risk factors (endometriosis, obesity, family history of breast/ovarian cancer, nulliparity, oral contraceptive use, and tubal ligation) and by number of risk factors (0, 1, 2 or more).
Overall, frequent aspirin use was associated with a 13% reduction in ovarian cancer risk (95% confidence interval [CI] 6 to 20), with no significant heterogeneity by study design (p = 0.48) or histotype (p = 0.60). Although no association was observed among women with endometriosis, consistent risk reductions were observed among all other subgroups defined by ovarian cancer risk factors (relative risks ranging from 0.79 to 0.93, all p heterogeneity > 0.05), including women with 2 or more risk factors (relative risk 0.81; 95% CI 0.73 to 0.90).
The authors commented that combined analyses of individual participant data from 17 study populations pointed to association of frequent aspirin use with a 13% reduction in ovarian cancer risk overall, and with a 14% reduction for high-grade serous carcinoma. Consistent risk reductions were observed across most subgroups of women with other ovarian cancer risk factors, with the exception of endometriosis. Among women with 2 or more risk factors, frequent aspirin use was associated with a 19% reduction in ovarian cancer risk. To maximise the population-level benefit/risk ratio, the use of aspirin for ovarian cancer chemoprevention may best be targeted to higher-risk women with 2 or more ovarian cancer risk factors.
These results suggest that primary prevention of ovarian cancer is an added benefit of frequent aspirin use that could be incorporated into composite risk-benefit calculations. Future work should explore how chemoprevention programmes with aspirin could complement existing preventive strategies, which are currently limited to women with the highest risk (e.g. prophylactic salpingo-oophorectomy for BRCA1/2 mutation carriers) and target additional high-risk subgroups to maximise population-level impact and minimise risks.
This analysis was funded by US Department of Defense Ovarian Cancer Research Program.
Hurwitz LM, Townsend MK, Jordan SJ, et al. Modification of the Association Between Frequent Aspirin Use and Ovarian Cancer Risk: A Meta-Analysis Using Individual-Level Data From Two Ovarian Cancer Consortia. JCO; Published online 22 July 2022. DOI: 10.1200/JCO.21.01900