Angiotensin Receptor Blockers Associated with Improved Breast Cancer Survival—A Nationwide Cohort Study from Finland

Abstract

Introduction: Breast cancer (BCa) has been associated with hypertension which might adversely affect disease prognosis. It is however unclear whether use of anti-HT drugs would improve BCa prognosis. Materials and Methods: A cohort of 73,170 women diagnosed BCa during 1995-2013 identified from the Finnish Cancer Registry and information on anti-HT drug use based on national prescription database during the same time period was combined. Anti-HT drug use was analysed separately by drug use before and after BCa diagnosis. Analyses were performed using timedependent variables for use of each six anti-HT drug group, statins, antidiabetic drugs and anticoagulative drugs to model for simultaneous use of multiple drugs. Association between cumulative dose, duration and intensity of anti-HT drug use and risk of BCa death was evaluated. Results: In pre-diagnostic use only ATR-blockers associated with decreased risk of BCa death compared to non-users (HR: 0.76 95% CI: 0.69-0.82) and risk decreased in inverse association with cumulative dose and duration of use. Diuretics and furosemide associated with statistically significant increase in BCa death risk.In post-diagnostic analyses ATR-blockers and also ACE-inhibitors, beta-blockers and calciumchannel blockers were associated with better BCa survival compared to non users. The results were dose-dependent in all mentioned drug groups. The risk decrease was however highest among users of ATR-blockers (HR: 0.69 95% CI: 0.63-0.75).Conclusions: ATR-blockers were the only antihypertensive drug group associated with improved BCa survival in both pre-and post-diagnostic use. The association was dose-dependent and supported by biological rationale which suggests a direct, causal explanation. However, for postdiagnostic use similar lowering was found also for other anti-HT groups which also supports prognostic role of hypertension control. Risk estimates for post-diagnostic ATR-blocker use were however lower compared to others drug groups. Inhibiting angiotensin receptor could be a promising novel way to affect risk of breast cancer progression. Table S1. DrugATC-code Enalapril C09AA02 ,

Post-Diagnostic Beta Blocker Use and Breast Cancer-Specific Mortality: A Population-Based Cohort Study

“…Our primary nding is consistent with a number of previous studies indicating no signi cant association between BB use and BCD in their fully adjusted analyses [16,20,[22][23][24][25], while a number have found BBs to be protective [16][17][18], and one to increase the risk of BCD [26]. For example, a study of 466 breast cancer patients in England found hypertensive patients treated with BBs to have a 71% reduction in BCD (HR=0.29; 0.12-0.71) [17].…”

“…On the basis of this evidence, several observational studies have been carried out, and some have reported that BB use may be protective for breast cancer-speci c death (BCD) [16][17][18][19]. However, others have noted no association between BBs and BCD [20][21][22][23][24][25], and one reported BBs were associated with an increased risk of BCD [26].…”

Association Between Antihypertensive Medication Use and Breast Cancer: A Systematic Review and Meta-Analysis

“…Studies found that thiazide diuretics, but not other diuretics, were linked to an increasing risk of breast cancer, and the authors considered the increase in insulin resistance due to thiazide diuretics as a possible explanation ( Sarafidis et al, 2007 ; Ni et al, 2017 ). A recent study showed that the use of furosemide or other diuretics before breast cancer diagnosis increased the risk of breast cancer-related death ( Santala et al, 2020 ). Our results showed that the breast cancer mortality increased with the use of diuretics; however, we failed to analyze the effect of diuretic subtypes on breast cancer prognosis because there were few relevant studies.…”

Post-diagnostic beta blocker use and breast cancer-specific mortality: a population-based cohort study

“…On the basis of this evidence, several observational studies have been carried out, and some have reported that BB use may be protective for breast cancer-specific death (BCD) [16][17][18][19]. However, others have noted no association between BBs and BCD [20][21][22][23][24][25], and one reported BBs were associated with an increased risk of BCD [26]. The only RCT carried out on BBs (to date) found that preoperative propranolol downregulated biomarkers of invasive potential and inflammation, and improved biomarkers of cellular immune response [27].…”