Use of beta-blockers, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers and breast cancer survival: Systematic review and meta-analysis

Breast cancer (BC) is the second leading cause of cancer death among women in Western Countries. Beta-blocker (BB) drugs, angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) were suggested to have a favorable role in the development and progression of BC. We have performed a meta-analysis to clarify the potential benefits of these drugs on BC survival. A total number of 46 265 BC patients from eleven papers were included, ten independent studies on BB use and seven on ACEi/ARB use. The summary hazard ratio (SHR) was estimated by pooling the study-specific estimates with random effects models and maximum likelihood estimation. We assessed the homogeneity of the effects across studies and evaluated between-study heterogeneity by meta-regression and sensitivity analyses. We found a significant improvement in BC specific survival for patients treated with BB drugs at the time of BC diagnosis (SHR: 0.44; 95%CI: 0.26-0.73 with I-2=78%). We also observed a borderline significant improvement in disease free survival for subjects treated with BB (SHR: 0.71, 95%CI: 0.19-1.03). No association of ACEi/ARB use with disease free and overall survival was found. In conclusion, we report epidemiological evidence that BB improve BC-specific survival. Clinical trials addressing this hypothesis are warranted. What's new? Antihypertensive drugs are linked to reductions in tumor metastasis, tumor recurrence and cancer-specific mortality, benefits possibly related to the drugs' ability to blunt the effects of stress hormones and inflammation. Results from previous observational studies are controversial, however, particularly concerning breast cancer and whether taking antihypertensive drugs can actually improve survival. In the present meta-analysis, which included some 46,265 patients from 11 articles, breast cancer-specific survival was found to be significantly improved among patients who were undergoing treatment with beta-blockers at the time of cancer diagnosis. The authors declare a need for further exploration in clinical trials.