Calcium channel blockers and breast cancer incidence: An updated systematic review and meta-analysis of the evidence

Abstract

Controversy exists regarding the potential association between taking calcium channel blockers (CCBs) and the development of breast cancer. As a positive association would have important public health implications due to the widespread use of CCBs, this study aimed to incorporate new evidence to determine whether an association is likely to exist. We searched MEDLINE, EMBASE and the Cochrane Library to 28 June 2016 for relevant literature. References and citing articles were checked and authors contacted as necessary. Two authors independently selected articles and extracted data. Twenty-nine studies were reviewed; 26 were non-randomised studies (NRS). Meta-analysis of study data where adjustment for 'confounding by indication' was judged to be present suggests that an association, if any, is likely to be modest in magnitude (pooled odds/risk ratio 1.09 (95% confidence interval (CI) 1.03-1.15, I=0%, 8 sub-studies; pooled hazard ratio 0.99 (95% CI 0.94-1.03, I=35%, 9 sub-studies)). There are credible study data showing an increased relative risk with long-term use of CCBs, but the results of our meta-analysis and of meta-regression of log relative risk against minimum follow-up time are mixed. The current summative evidence does not support a clear association between taking CCBs and developing breast cancer. However, uncertainty remains, especially for long-term use and any association might not be uniform between different populations and/or breast cancer sub-types. We thus recommend further NRS in settings where CCB use is highly prevalent and population-based cancer, prescription and health-registries exist, to resolve this continuing uncertainty. PROSPERO, CRD42015026712.

Incidence, Risk Factors, and Outcomes of Cancer in Systemic Sclerosis

“…The association between the extended use of CCBs and overall cancer (OR 1.46, P = 0.016), breast cancer (OR 1.61, P = 0.051), and melanoma (OR 2.01, P = 0.042) in our cohort was unexpected, but has been reported in the literature with conflicting results (19)(20)(21). This association is hypothesized to be related to the role of calcium in cell apoptosis, such as activation of the caspase pathway, induction of endonuclease activity, and mitochondrial permeation.…”

Biphasic Temporal Relationship between Cancers and Systemic Sclerosis: A Clinical Series from Montpellier University Hospital and Review of the Literature

“…In the present study, a significant number of "late-onset" cancers were associated with immunosuppressive treatments (including azathioprine and cyclophosphamide, Supplemental Table S2b). Calcium channel blockers (CCB) have also been proposed to explain an over-risk of cancer among SSc patients, especially breast cancer [11,21,36]. In their recent study of 1727 SSc patients, Morrisroe and colleagues found a significant difference in the use of calcium channel blockers between patients with cancer (n = 245) compared to patients without cancer (n = 1482), and especially in the case of prolonged use (p < 0.001, univariate analysis) [9].…”

Objectives, design and main findings until 2020 from the Rotterdam Study

“…In the near future, we will focus on 2 research topics. First, etiologically, we will investigate the role of drug use on the occurrence of cancer, especially use of long-term treatment such as calcium antagonists [47]. Furthermore, we will extend our investigation on the role of genetic determinants, diet and (inflammatory) biomarkers and the risk of cancer.…”