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Cancer Epidemiology, Biomarkers & Prevention
Cancer Epidemiology, Biomarkers & Prevention
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Angiotensin Receptor Blockers Associated with Improved Breast Cancer Survival—A Nationwide Cohort Study from Finland

Eerik E.E. Santala, Mika O. Murto, Miia Artama, Eero Pukkala, Kala Visvanathan and Teemu J. Murtola
Eerik E.E. Santala
1Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
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  • For correspondence: eerik.santala@tuni.fi
Mika O. Murto
2Tampere University Hospital, Tampere, Finland.
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  • ORCID record for Mika O. Murto
Miia Artama
3National Institute of Health and Welfare, Helsinki, Finland.
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Eero Pukkala
4Finnish Cancer Registry, Helsinki, Finland.
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Kala Visvanathan
5Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
6Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, Maryland.
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Teemu J. Murtola
1Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
2Tampere University Hospital, Tampere, Finland.
7Seinäjoki Central Hospital, Department of Urology, Seinäjoki, Finland.
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DOI: 10.1158/1055-9965.EPI-20-0711 Published November 2020
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Abstract

Background: Breast cancer incidence has been associated with hypertension, which might worsen disease prognosis, but few nationwide studies have investigated the association between antihypertensive drug use and breast cancer prognosis.

Methods: A cohort of 73,170 women diagnosed with breast cancer during 1995–2013 identified from the Finnish Cancer Registry was combined with information on antihypertensive drug use during the same time period from a national prescription database. Antihypertensive drugs were analyzed in groups categorized by mechanism of action. Usage of antihypertensive drugs, statins, antidiabetic, and anticoagulative drugs was analyzed as time-dependent exposure to model for simultaneous use of multiple drug groups. Influence of protopathic bias was evaluated in lag-time analyses.

Results: In prediagnostic use, only angiotensin receptor (ATR)-blockers were associated with decreased risk of breast cancer death as compared with nonusers (HR: 0.76, 95% confidence interval, CI: 0.69–0.82), and there was an inverse association with cumulative dose of use. Postdiagnostic use of ATR-blockers, angiotensin-converting enzyme (ACE)-inhibitors, beta-blockers, and calcium-channel blockers was dose dependently associated with better breast cancer survival compared with nonusers. The risk decrease was strongest for ATR-blockers (HR: 0.69, 95% CI: 0.63–0.75) and remained for exposures occurring up to 3 years earlier.

Conclusions: Only ATR-blockers were associated with improved breast cancer survival in both prediagnostic and postdiagnostic use. The association was dose dependent and supported by a biological rationale as a causal explanation. In postdiagnostic use, similar reduction was found also for other antihypertensives, supporting a prognostic role of hypertension control.

Impact: Inhibition of angiotensin receptor subtype 1 (AT1) could be a promising novel way to affect breast cancer progression.

Footnotes

  • Note: Supplementary data for this article are available at Cancer Epidemiology, Biomarkers & Prevention Online (http://cebp.aacrjournals.org/).

  • Cancer Epidemiol Biomarkers Prev 2020;29:2376–82

  • Received May 11, 2020.
  • Revision received July 3, 2020.
  • Accepted August 21, 2020.
  • Published first September 11, 2020.
  • ©2020 American Association for Cancer Research.
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Cancer Epidemiology Biomarkers & Prevention: 29 (11)
November 2020
Volume 29, Issue 11
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Angiotensin Receptor Blockers Associated with Improved Breast Cancer Survival—A Nationwide Cohort Study from Finland
Eerik E.E. Santala, Mika O. Murto, Miia Artama, Eero Pukkala, Kala Visvanathan and Teemu J. Murtola
Cancer Epidemiol Biomarkers Prev November 1 2020 (29) (11) 2376-2382; DOI: 10.1158/1055-9965.EPI-20-0711

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Angiotensin Receptor Blockers Associated with Improved Breast Cancer Survival—A Nationwide Cohort Study from Finland
Eerik E.E. Santala, Mika O. Murto, Miia Artama, Eero Pukkala, Kala Visvanathan and Teemu J. Murtola
Cancer Epidemiol Biomarkers Prev November 1 2020 (29) (11) 2376-2382; DOI: 10.1158/1055-9965.EPI-20-0711
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