Abstract IA10: Precision chemoprevention with aspirin

Abstract

Abstract Remarkably consistent experimental and epidemiologic evidence demonstrates that aspirin is associated with a lower risk of colorectal cancer. Five placebo-controlled randomized controlled trials (RCTs) among individuals with a history of colorectal neoplasia showed that aspirin reduced the risk of recurrent adenomatous polyps, the precursors of the vast majority of cancers. Additionally, data from long-term follow-up of a RCT of aspirin among individuals with the Lynch hereditary colorectal cancer syndrome and a RCT of aspirin among women for primary prevention of cardiovascular disease and cancer demonstrated a lower risk of colorectal cancer associated with randomized aspirin treatment. As a reflection of the strength of the evidence, the U.S. Preventative Services Task Force (USPSTF) updated its primary prevention guidelines for aspirin in 2016. The USPSTF provided low-dose aspirin (81 mg/day) with a recommendation for chronic disease prophylaxis, including colorectal cancer prevention, among U.S. adults between ages 50-59, and possibly ages 60-69, with a greater than 10% ten-year risk of cardiovascular events. The new USPSTF recommendation represents a significant milestone for the field of preventive medicine. With the exception of tamoxifen for women at high-risk for breast cancer, this is the first medication recommended for cancer prevention by USPSTF guidelines. Despite this advance, broader recommendations for aspirin chemoprevention are limited by concerns about risk-benefit profile in view of the established association of aspirin with gastrointestinal bleeding. Thus, in concert with broader efforts to tailor prevention strategies, our group has led several studies into the mechanistic basis of aspirin's anti-cancer effect that has led to the development of intratumoral, germline, and circulating molecular correlates of outcomes. Such biomarkers can be exploited for risk stratification to more effectively target aspirin chemoprevention for those with more favorable risk-benefit profiles. In this presentation, we will review the evidence supporting a role for aspirin in the prevention and treatment of cancer, with a focus on novel strategies for molecular risk stratification. Citation Format: Andrew T. Chan. Precision chemoprevention with aspirin. [abstract]. In: Proceedings of the AACR Special Conference on Colorectal Cancer: From Initiation to Outcomes; 2016 Sep 17-20; Tampa, FL. Philadelphia (PA): AACR; Cancer Res 2017;77(3 Suppl):Abstract nr IA10.