The Influence of BRAF and KRAS Mutation Status on the Association between Aspirin Use and Survival after Colon Cancer Diagnosis.

Martine A Frouws,Hans Morreau,Gerrit-Jan Liefers,Tom Van Wezel,Myrthe P P Van Herk-Sukel,Ronald Van Eijk,Valery E P P Lemmens,Marloes Swets,Cornelis J H Van De Velde,Marlies S Reimers,Esther Bastiaannet,Bianca Prinse,Peter J K Kuppen

doi:10.1371/journal.pone.0170775

Abstract

BackgroundUse of aspirin after diagnosis of colon cancer has been associated with improved survival. Identification of cancer subtypes that respond to aspirin treatment may help develop personalized treatment regimens. The aim of this study was to investigate the influence of BRAF and KRAS mutation status on the association between aspirin use and overall survival after colon cancer diagnosis.MethodsA random selection of 599 patients with colon cancer were analyzed, selected from the Eindhoven Cancer Registry, and BRAF and KRAS mutation status was determined. Data on aspirin use (80 mg) were obtained from the PHARMO Database Network. Parametric survival models with exponential (Poisson) distribution were used.ResultsAspirin use after colon cancer diagnosis was associated with improved overall survival in wild-type BRAF tumors, adjusted rate ratio (RR) of 0.60 (95% CI 0.44–0.83). In contrast, aspirin use in BRAF mutated tumors was not associated with an improved survival (RR 1.11, 95% CI 0.57–2.16). P-value for interaction was non-significant. KRAS mutational status did not differentiate in the association between aspirin use and survival.ConclusionLow-dose aspirin use after colon cancer diagnosis was associated with improved survival in BRAF wild-type tumors only. However, the large confidence interval of the rate ratio for the use of aspirin in patients with BRAF mutation does not rule out a possible benefit. These results preclude BRAF and KRAS mutation status to be used as a marker for individualized treatment with aspirin, if aspirin becomes regular adjuvant treatment for colon cancer patients in the future.

Highlights

A significant body of proof has already demonstrated that aspirin has anticancer effects in colorectal cancer (CRC) [1,2,3,4,5]
Aspirin use after colon cancer diagnosis was associated with improved overall survival in wild-type BRAF tumors, adjusted rate ratio (RR) of 0.60
Aspirin use in BRAF mutated tumors was not associated with an improved survival (RR 1.11, 95% Confidence Interval (CI) 0.57–2.16)

Summary

Introduction

A significant body of proof has already demonstrated that aspirin has anticancer effects in colorectal cancer (CRC) [1,2,3,4,5]. Randomized controlled trials investigating the cardiovascular benefits of aspirin have shown a significant reduction of CRC risk and mortality [1, 6, 7]. The most recent meta-analysis of observational studies by Elwood et al found a 25% reduction in colorectal cancer-related deaths and a 20% overall mortality reduction [4] These publications have led to several ongoing randomized controlled trials studying the effect of aspirin on cancer mortality which are currently being conducted globally: the Add-Aspirin trial [9], Adjuvant Aspirin for Colon Cancer (NCT02467582), the ALASCCA trial (NCT02647099), the ASCOLT trial (NCT00565708), and the Aspirin trial (NCT02301286). The aim of this study was to investigate the influence of BRAF and KRAS mutation status on the association between aspirin use and overall survival after colon cancer diagnosis

Objectives

Methods

Conclusion