Preliminary evidence from retrospective studies indicates a possible favorable role of beta-blockers (BB) in improving the prognosis of patients with breast cancer (BC). The mechanisms behind such a possible beneficial effect are speculative and may include inhibition of angiogenesis, stimulation of T-cell recruitment, increases in the production of proinflammatory cytokines, and induction of immune activation. However, meta-analyses that have examined the role of BB in BC have yielded conflicting results.
Investigators conducted a systematic review and meta-analysis to assess the impact of BB on the outcomes of patients with early-stage breast cancer (EBC). A literature search was conducted utilizing PubMed, Embase, the Cochrane Library, and proceedings from major oncology conferences. Data collection was censored at October 31, 2020. To be included, clinical trials had to be published, presented, or otherwise have publicly available data; had to report patient outcomes for at least one endpoint in the meta-analysis; and had to only include or at least report on patients with EBC.
The primary objective of the study was to compare the outcomes of patients with EBC who received BB to those who did not. The primary endpoint was recurrence-free survival (RFS), which was the occurrence of either a BC recurrence or death, whichever came first. Secondary objectives included pathological complete response (pCR), BC recurrence, BC-specific mortality, and overall survival (OS).
A total of 13 studies were included of patients with EBC. Six studies, which included a total of 21,570 subjects, examined RFS according to BB use for the overall population. Use of the cardiac medications was associated with a significant 27% increase in RFS; following sensitivity analysis, this increased to 33%. Three studies, accounting for 1,213 study participants, found that BB use significantly improved RFS by 47% for patient with triple-negative EBC. There was no difference between selective and nonselective BB on RFS based on the results of two studies that included 12,067 patients.
Two studies, including 1,554 participants, found that BB use significantly improved pCR by 23%. Six studies including 37,957 patients examined the role of BB in BC recurrence and found that they significantly reduced recurrence by 34%; this increased to 41% when heterogeneity was eliminated. A significant 23% reduction in BC-specific mortality was observed with the use of BB based on seven studies that included 64,830 subjects. This increased to 33% following the exclusion of one study that included low-risk patients. No significant difference in OS was observed with the use of BB as assessed in five studies, which included 103,065 patients. Following a sensitivity analysis that removed one study, BB use was associated with worse OS.
As pharmacists continue to work with other members of the healthcare team to identify therapeutic options in the management of patients with EBC, this study provides preliminary evidence of possible benefit for the repurposed use of BB, especially in patients with triple-negative EBC.
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