PT  - JOURNAL ARTICLE
AU  - Santala, Eerik E.E.
AU  - Murto, Mika O.
AU  - Artama, Miia
AU  - Pukkala, Eero
AU  - Visvanathan, Kala
AU  - Murtola, Teemu J.
TI  - Angiotensin Receptor Blockers Associated with Improved Breast Cancer Survival—A Nationwide Cohort Study from Finland
AID  - 10.1158/1055-9965.EPI-20-0711
DP  - 2020 Nov 01
TA  - Cancer Epidemiology Biomarkers & Prevention
PG  - 2376--2382
VI  - 29
IP  - 11
4099  - http://cebp.aacrjournals.org/content/29/11/2376.short
4100  - http://cebp.aacrjournals.org/content/29/11/2376.full
SO  - Cancer Epidemiol Biomarkers Prev2020 Nov 01; 29
AB  - 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.