Abstract IA5: Aspirin for precision chemoprevention of colorectal cancer

Abstract

Abstract Remarkably consistent experimental and epidemiologic evidence demonstrates that aspirin is associated with a lower risk of colorectal cancer. These studies have been complemented by compelling data from randomized controlled trials (RCTs). Five placebo-controlled RCTs among individuals with a history of colorectal adenoma or cancer showed that aspirin reduced the risk of recurrent adenomas, the precursors of the vast majority of cancers. Data from long-term follow-up of the CAPP2 trial, a RCT of aspirin among individuals with the Lynch hereditary colorectal cancer syndrome and the Women's Health Study, a RCT of aspirin among women for primary prevention of cardiovascular disease and cancer demonstrated that randomized aspirin treatment was associated with a lower risk of colorectal cancer. Finally, secondary analyses of RCTs of aspirin for cardiovascular prevention have shown that aspirin reduces incidence of and mortality from colorectal cancer. As a reflection of the strength of the evidence, the U.S. Preventive Services Task Force (USPSTF) updated its primary prevention guidelines for aspirin in 2016. The USPSTF now recommends low-dose aspirin (81 mg/day) 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 broadly recommended for cancer prevention by the USPSTF. Despite this advance, wider scale efforts to implement aspirin chemoprevention are limited by concerns about risk-benefit profile in view of the established association of aspirin with gastrointestinal bleeding. 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, colonic, 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 of colorectal cancer, with a focus on novel methods for molecular risk stratification. Such a precision chemoprevention strategy could play a role in global efforts for chronic disease prevention and control. Citation Format: Andrew T. Chan. Aspirin for precision chemoprevention of colorectal cancer [abstract]. In: Proceedings of the AACR International Conference: New Frontiers in Cancer Research; 2017 Jan 18-22; Cape Town, South Africa. Philadelphia (PA): AACR; Cancer Res 2017;77(22 Suppl):Abstract nr IA5.