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

Abstract

Background: The prevalence rate of hypertension and breast cancer increases with advancing age. Renin-angiotensin system inhibitors (RASIs), β-blockers (BBs), calcium channel blockers (CCBs), and diuretics are widely used to treat patients with hypertension. Although, the association between the use of antihypertensive medication and breast cancer has been highly debated, recent evidence supporting this association remains controversial.Objective: To evaluate the association between the use of antihypertensive medication and the risk of breast cancer and its prognosis.Methods: This study was conducted using data from the PubMed, Embase, and Cochrane Library databases retrieved for the period from January 2000 to April 2021. Articles and their references were checked and summary effects were calculated using random- and fixed-effects models. Heterogeneity test and sensitivity analysis were also performed.Results: This meta-analysis included 57 articles, which were all related to breast cancer risk or prognosis. Assessment of breast cancer risk using the pooled data showed that the use of BBs or CCBs or diuretics was associated with increased cancer risk [BB: relative risk (RR) = 1.20, 95% confidence interval (CI) = 1.09–1.32; CCBs: RR = 1.06, 95% CI 1.03–1.08; diuretics: RR = 1.06, 95% CI 1.01–1.11]. Long-term use of diuretic increased the risk of breast cancer (RR = 1.10, 95% CI 1.01–1.20), whereas long-term RASIs treatment reduced the risk (RR = 0.78, 95% CI 0.68–0.91). In addition, we found that diuretic users may be related to elevated breast cancer-specific mortality [hazard ratio (HR) = 1.18, 95% CI 1.04–1.33], whereas using other antihypertensive medications was not associated with this prognosis in patients with breast cancer.Conclusion: Using CCBs, BBs, and diuretics increased the risk of breast cancer. In addition, diuretics may elevate the risk of breast cancer-specific mortality. The long-term use of RASIs was associated with a significantly lower breast cancer risk, compared with non-users. Thus, this analysis provides evidence to support the benefits of the routine use of RASIs in patients with hypertension, which has important public health implications.

Association of Hypertension and Breast Cancer: Antihypertensive Drugs as an Effective Adjunctive in Breast Cancer Therapy

“…Studies have reported that women who used antihypertensive medications showed an increased improvement in the BC treatment compared to those without prescriptions of antihypertensive drugs. 31 , 34 …”

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

“…For example, health registries and EHR are often very large and matched to contemporary practice, but may have limited value with regards to treatment, comorbidity, cancer subtype, and other adjustment data to extract causality insights (as compared to some trial datasets) (Mack et al, 2018). As such, it would be useful if Xie et al (2021) provides clear information on the data types used in each metastudy and whether results differ according to registry/EHR versus clinical trial data.…”

“…We note that Cardwell et al (2014) and Cui et al (2019) provide explicit statements on their methodologies to account for immortal time bias (nested case-control and time-dependent approach respectively). We would appreciate it if Xie et al (2021) could provide information on whether each study used methodologies to mitigate immortal time bias, and whether meta-analysis results differed between studies that did and did not account for immortal time bias.…”

“…However, undertaking randomised control trials to identify the impact of each non-cancer concomitant medicine on breast cancer prognosis is not practicable due to cost, exposure to potentially harmful strategies, and years until results become apparent. Thus, we read with great interest the systematic review and meta-analysis from Xie et al on the association between concomitant antihypertensive medication use and breast cancer risk and prognosis (breast cancerspecific mortality, recurrence, overall survival, and disease-specific survival) (Xie et al, 2021). Xie et al (2021) concluded that the use of calcium channel blockers, beta-blockers, or diuretics was significantly associated with an increased risk of developing breast cancer, and that diuretic use may elevate the risk of breast cancer-specific mortality (with no statistically significant association found for calcium channel blockers, beta-blockers, or reninangiotensin system inhibitors).…”

“…Thus, we read with great interest the systematic review and meta-analysis from Xie et al on the association between concomitant antihypertensive medication use and breast cancer risk and prognosis (breast cancerspecific mortality, recurrence, overall survival, and disease-specific survival) (Xie et al, 2021). Xie et al (2021) concluded that the use of calcium channel blockers, beta-blockers, or diuretics was significantly associated with an increased risk of developing breast cancer, and that diuretic use may elevate the risk of breast cancer-specific mortality (with no statistically significant association found for calcium channel blockers, beta-blockers, or reninangiotensin system inhibitors). Underlying assumptions of these conclusions are that the meta-analysis strategy acquired sufficient power to assess the associations and the author team adequately evaluated and filtered original scientific literature for quality.…”