Rationale and Objective: Ovarian cancer is the most fatal cancer affecting women, largely due to the symptoms of the disease, like pain and pressure, being common and therefore leading to delays in diagnosis. Currently, there are no tests to detect early-stage ovarian cancer and no ways to prevent it, though women with higher risk of the disease, such as those with genetic mutations in the BRCA1 or BRCA2 genes, can have surgery to remove their ovaries. However, this surgery leads to infertility and early menopause. There is a great need to find prevention strategies to reduce the number of women being diagnosed with ovarian cancer. Chemoprevention is the prevention of a disease through medication use. Aspirin is one such medication; it is affordable and used to prevent heart attacks in people who are at high risk of getting them. Scientific research from the last few years indicates that aspirin may also reduce the risk for ovarian cancer, but more research is needed before aspirin can officially be recommended to patients by their doctors.

Problem to Be Addressed and How It Will Advance the Field: The objectives of our project, therefore, are to address the following unresolved questions regarding aspirin and ovarian cancer: (1) to understand the influence of daily aspirin use on the long time-course of ovarian cancer development; (2) to identify groups of women that will receive the most benefit from aspirin chemoprevention; and (3) to evaluate whether aspirin’s ability to reduce inflammation or alter the immune microenvironment are reasons for reduced ovarian cancer risk, all of which will have the potential to provide evidence to clinical and public health decision-making organizations to support the use of aspirin to prevent ovarian cancer.

This investigator-initiated application proposes to address these aims by combining data from large ovarian cancer consortia with previously collected detailed information on medication use, lifestyle factors, and ovarian cancer outcomes. We will create a comprehensive resource to conduct well-powered (large) and well-designed investigations evaluating aspirin use and ovarian cancer risk. These investigations will clarify the appropriate age or time period of medication use for maximal ovarian cancer risk reduction and identify high-risk groups of women that will benefit most from aspirin use to prevent ovarian cancer. In addition to the collection of high-quality data, tumor specimens collected from a subset of studies will be utilized to evaluate the interplay between aspirin use and the tumor immune environment that will help us understand the biologic ways (mechanisms) that aspirin prevents ovarian cancer.

Clinical Applications, Benefits, and Risks: Since aspirin generally has few side effects, the potential for public health impact is substantial. Identifying groups of women that will receive the most benefit from aspirin use with respect to ovarian cancer means that doctors can target their recommendations. Further, low-dose/daily aspirin use is already recommended to lower risk of heart disease and colorectal cancer. If our results further support that daily aspirin use directly influences ovarian cancer risk, this will provide additional justification for using aspirin, a medication that is affordable and easy to purchase, to prevent multiple diseases.

By clarifying the extent to which daily aspirin use can reduce ovarian cancer risk and identifying subgroups of women who will gain the most benefit from a daily aspirin regimen, this research will inform future clinical trials to evaluate the ability of aspirin to prevent ovarian cancer in high-risk women. By understanding the mechanism through which aspirin affects the ovarian cancer tumor environment, this work may also inform potential co-testing of immune-modulators and daily aspirin use to improve survival in ovarian cancer patients.

Impact of Proposed Research on Health and Well-Being of Service Members, Veterans, Retirees, Their Family Members, and All Women Impacted by This Disease: This innovative application combines epidemiologic and tumor tissue data to conduct a well-powered investigation of aspirin use with ovarian cancer risk that will improve both the mechanistic understanding of the development of ovarian cancer and the ability to make recommendations regarding prevention of this fatal disease. The impact of our proposal is enhanced by its methodological innovation and rigor. The extensive resources we are leveraging, combined with our experienced team and multidisciplinary focus, will help us to better identify women who would be most likely to benefit from aspirin. The proposed research will benefit all women, including military Service members, their families, and other military beneficiaries.