Post-Diagnostic Beta Blocker Use and Prognosis of Ovarian Cancer: A Systematic Review and Meta-Analysis of 11 Cohort Studies With 20,274 Patients

Abstract

ObjectivesPrevious experimental studies have indicated that exposure to beta blocker provides protective effects against ovarian cancer (OC). However, findings from epidemiologic studies have still been controversial. Therefore, we carried out a meta-analysis to update and quantify the correlation between post-diagnostic beta blocker usage and OC prognosis.MethodsThe meta-analysis had been registered at PROSPEPO. The number of registration is CRD42020188806. A comprehensive search of available literatures in English prior to April 16, 2020, was conducted in PubMed, EMBASE, and the Web of Science databases. Random-effects models were used to calculate overall hazard ratios (HRs) and 95% confidence intervals (CIs). Publication bias assessments, and subgroup, sensitivity, and meta-regression analyses were also performed.ResultsOf the 637 initially identified articles, 11 retrospective cohort studies with 20,274 OC patients were included. The summary HRs did not reveal any statistically significant associations between post-diagnostic beta blocker use and OC prognosis characteristics, such as total mortality (HR = 1.08, 95% CI = 0.92–1.27, I2 = 76.5%, n = 9), cancer-specific mortality (HR = 1.22, 95% CI = 0.89–1.67, I2 = 88.1%, n=3), and progression-free survival (HR = 0.88, 95% CI = 0.75–1.05, I2 = 0, n = 4). No evidence of publication bias was observed in current analysis. In our subgroup analyses, the majority of results were consistent with the main findings. However, several positive correlations were detected in studies with ≥800 cases (HR = 1.20, 95% CI = 1.05–1.37), no immortal time bias (HR = 1.28, 95% CI = 1.10–1.49), and adjustment for comorbidity (HR = 1.20, 95% CI = 1.05–1.37). In the meta-regression analysis, no evidence of heterogeneity was detected in the subgroups according to study characteristics and confounding factors.ConclusionsPost-diagnostic beta blocker use has no statistical correlation with OC prognosis. More prospective cohort studies are necessary to further verify our results.Systematic Review RegistrationIdentifier (CRD42020188806).

Evaluation of antihypertensive medications use and survival in patients with ovarian cancer: a population-based retrospective cohort study

“…We found that the use of both ACE inhibitors and ARBs during first year after diagnosis had a significantly greater benefit on survival compared to each medication class alone, although the result was based on few outcomes. The possible mechanisms underlying the observed reduction of cancer-specific death risk following the ARB and ACE inhibitors medication use include reduction of inflammation, tumour angiogenesis, invasion and peritoneal dissemination in human ovarian cancer cells by blockage of angiotensin receptors (both Angiotensin II type 1 receptor (AT1R) and Angiotensin II type 2 receptor (AT2R)) [ 6 , 12 ]. According to Suganuma et al, AT1R expression has been observed in 85% of invasive ovarian carcinomas, whereas it was not detected on surface epithelium of the normal ovary [ 23 ].…”

“…Studies analysing the association between the use of BBs and survival among ovarian cancer patients report contradictory results. In most studies BBs users showed no association [ 6 , 7 , 9 , 12 , 13 ] or better survival outcomes [ 10 , 25 , 26 ]. A study by Harding et al (2018) found ovarian cancer-specific mortality to be lower among women who used nonselective BBs, but not in selective BBs users [ 8 ].…”

“…The results of several recent studies suggested survival benefits for BBs users, particularly for nonselective BBs users [ 8 , 10 , 11 ]. In contrast, some investigators found no association [ 12 ] or a significant positive association, especially for selective BBs [ 10 , 13 – 15 ]. In recent meta-analyses it was concluded, that there is insufficient evidence regarding the association between ACE inhibitors or BBs and ovarian cancer survival [ 12 , 16 ].…”

“…In contrast, some investigators found no association [ 12 ] or a significant positive association, especially for selective BBs [ 10 , 13 – 15 ]. In recent meta-analyses it was concluded, that there is insufficient evidence regarding the association between ACE inhibitors or BBs and ovarian cancer survival [ 12 , 16 ]. Consumption of other antihypertensive drug groups (calcium channel blockers (CCBs) or diuretics) was not associated with a decreased ovarian cancer death risk, except the elevated risk observed with furosemide use [ 6 , 7 , 9 ].…”

Beta-blockers in cardiac arrhythmias–Clinical pharmacologist’s point of view

“…The effect of beta-blockers on breast, ovarian, colorectal and pancreatic cancer has been investigated in observational studies ( Wen et al, 2021 ). In studies, propranolol has been shown to inhibit cell proliferation, and the combination of propranolol, docetaxel and doxorubicin in the treatment of various soft tissue sarcomas resulted in a better response to treatment, the most sensitive were angiosarcoma and liposarcoma ( Porcelli et al, 2020 ).…”