Beta-blockers in early-stage breast cancer: a systematic review and meta-analysis

Abstract

Background

Preclinical and retrospective studies suggest that beta-blockers are active against breast cancer. We carried out a systematic review and meta-analysis to assess the impact of beta-blockers on the outcomes of patients with early-stage breast cancer.

Methods

A systematic literature search was performed to identify studies comparing outcomes of patients with early-stage breast cancer according to beta-blocker use (yes versus no). The primary endpoint was recurrence-free survival (RFS), defined as the occurrence of breast cancer recurrence or death. Secondary objectives were pathologic complete response (pCR), breast cancer recurrence, breast cancer-specific mortality and overall survival (OS). Hazard ratios (HRs) or odds ratios (ORs) and 95% confidence intervals (CIs) were extracted from each study and a pooled analysis with the random-effect model was conducted. The Higgins' I-squared test was used to quantify heterogeneity. Egger's test was applied to assess publication bias. All P values were two-sided and considered significant if ≤0.05.

Results

Overall, 13 studies were included as follows: RFS (6), pCR (2), breast cancer recurrence (6), breast cancer-specific mortality (7) and OS (5). The use of beta-blockers was associated with a significant RFS improvement in the overall population ( N = 21 570; HR 0.73; 95% CI, 0.56-0.96; P = 0.025) and in patients with triple-negative disease ( N = 1212; HR 0.53; 95% CI, 0.35-0.81; P = 0.003). No significant differences in terms of pCR ( N = 1554; OR 0.77; 95% CI, 0.44-1.36; P = 0.371), breast cancer recurrence ( N = 37 957; OR 0.66; 95% CI, 0.42-1.03; P = 0.065), breast cancer-specific mortality ( N = 64 830; HR 0.77; 95% CI, 0.56-1.08; P = 0.130) or OS ( N = 103 065; HR 1.03; 95% CI, 0.87-1.23; P = 0.692) were observed according to beta-blocker use.

Discussion

In this meta-analysis, beta-blocker use was associated with a longer RFS in patients with early-stage breast cancer, with a more pronounced effect observed in those with triple-negative disease. Beta-blockers arise as an interesting option to be explored in prospective studies for patients with early-stage breast cancer.

Highlights

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  Beta-blockers inhibit proliferation, invasiveness and angiogenesis in preclinical models of breast cancer.

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  Retrospective studies suggest that beta-blocker use may improve the prognosis of patients with breast cancer.

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  In this meta-analysis, beta-blocker use was associated with an RFS improvement in patients with early-stage breast cancer.

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  A more pronounced prognostic effect of beta-blocker use was observed in patients with triple-negative disease.

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  Beta-blockers arise as a low-cost and safe option to be repositioned for the treatment of early-stage breast cancer.