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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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