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

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

doi:10.1371/journal.pone.0170775

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

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

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

BACKGROUND: Use 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.

METHODS: A 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.

RESULTS: Aspirin 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.

CONCLUSION: Low-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.

Original language	English
Article number	e0170775
Pages (from-to)	e0170775
Journal	PLoS ONE [E]
Volume	12
Issue number	1
DOIs	https://doi.org/10.1371/journal.pone.0170775
Publication status	Published - 2017
Externally published	Yes

Keywords

Journal Article

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10.1371/journal.pone.0170775

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Frouws, M. A., Reimers, M. S., Swets, M., Bastiaannet, E., Prinse, B., van Eijk, R., Lemmens, V. E. P. P., van Herk-Sukel, M. P. P., van Wezel, T., Kuppen, P. J. K., Morreau, H., van de Velde, C. J. H., & Liefers, G.-J. (2017). The Influence of BRAF and KRAS Mutation Status on the Association between Aspirin Use and Survival after Colon Cancer Diagnosis. PLoS ONE [E], 12(1), e0170775. Article e0170775. https://doi.org/10.1371/journal.pone.0170775

@article{6aa4c047e0ac4a3e9374e0a7b48414cb,

title = "The Influence of BRAF and KRAS Mutation Status on the Association between Aspirin Use and Survival after Colon Cancer Diagnosis",

abstract = "BACKGROUND: Use 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.METHODS: A 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.RESULTS: Aspirin 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.CONCLUSION: Low-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.",

keywords = "Journal Article",

author = "Frouws, \{Martine A\} and Reimers, \{Marlies S\} and Marloes Swets and Esther Bastiaannet and Bianca Prinse and \{van Eijk\}, Ronald and Lemmens, \{Valery E P P\} and \{van Herk-Sukel\}, \{Myrthe P P\} and \{van Wezel\}, Tom and Kuppen, \{Peter J K\} and Hans Morreau and \{van de Velde\}, \{Cornelis J H\} and Gerrit-Jan Liefers",

note = "Publisher Copyright: {\textcopyright} 2017 Frouws et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.",

year = "2017",

doi = "10.1371/journal.pone.0170775",

language = "English",

volume = "12",

pages = "e0170775",

journal = "PLoS ONE [E]",

issn = "1932-6203",

publisher = "Public Library of Science",

number = "1",

}

Frouws, MA, Reimers, MS, Swets, M, Bastiaannet, E, Prinse, B, van Eijk, R, Lemmens, VEPP, van Herk-Sukel, MPP, van Wezel, T, Kuppen, PJK, Morreau, H, van de Velde, CJH & Liefers, G-J 2017, 'The Influence of BRAF and KRAS Mutation Status on the Association between Aspirin Use and Survival after Colon Cancer Diagnosis', PLoS ONE [E], vol. 12, no. 1, e0170775, pp. e0170775. https://doi.org/10.1371/journal.pone.0170775

TY - JOUR

T1 - The Influence of BRAF and KRAS Mutation Status on the Association between Aspirin Use and Survival after Colon Cancer Diagnosis

AU - Frouws, Martine A

AU - Reimers, Marlies S

AU - Swets, Marloes

AU - Bastiaannet, Esther

AU - Prinse, Bianca

AU - van Eijk, Ronald

AU - Lemmens, Valery E P P

AU - van Herk-Sukel, Myrthe P P

AU - van Wezel, Tom

AU - Kuppen, Peter J K

AU - Morreau, Hans

AU - van de Velde, Cornelis J H

AU - Liefers, Gerrit-Jan

N1 - Publisher Copyright: © 2017 Frouws et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

PY - 2017

Y1 - 2017

N2 - BACKGROUND: Use 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.METHODS: A 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.RESULTS: Aspirin 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.CONCLUSION: Low-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.

AB - BACKGROUND: Use 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.METHODS: A 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.RESULTS: Aspirin 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.CONCLUSION: Low-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.

KW - Journal Article

U2 - 10.1371/journal.pone.0170775

DO - 10.1371/journal.pone.0170775

M3 - Article

C2 - 28125730

SN - 1932-6203

VL - 12

SP - e0170775

JO - PLoS ONE [E]

JF - PLoS ONE [E]

IS - 1

M1 - e0170775

ER -

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

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