Introduction:
Calcium channel blockers (CCBs) are a mainstay in treating hypertension (HTN). Recently, Li et-al published a population based case-control study (JAMA 2013; 289:2354) reporting CCB use to be associated with incident breast cancer (odds ratio 2.6). We prospectively analyzed 2 Intermountain Healthcare (IHC) databases (db) to confirm or refute this provocative report.
Methods:
Two separate analyses were conducted using general patients (GP) seen at IHC and patients undergoing coronary angiography (CV) at IHC facilities. Subjects were females aged 50-70 with no history of breast cancer. Those prescribed CCB were matched 1:1 to subjects not on CCB based on age, race, tobacco, alcohol, body mass index, HTN and follow up time. Multivariable Cox proportional hazards regression was used for the primary analysis of time to incident breast cancer by CCB use adjusting for history of other cancers and family history of breast cancer.
Results:
A total of 2612 GP subjects (cases/controls) and 1106 CV subjects (cases/controls) were studied. In the GP db, there was a statistically significant increased risk of breast cancer for subjects using CCB (HR=1.58; 95% CI: 1.10-2.26). Risk was also associated with a positive family history (HR=2.79; 1.96-3.97) and a personal history of cancer (HR=1.87; 1.07-3.26). Breast cancer predominantly developed in <5 y of follow up (64% of cases). However, a reverse relationship was found in the CV db, where the HR was 0.51 (95% CI: 0.27-0.97). This observation was found despite consistent associations with several secondary outcomes, including for incident diabetes, coronary and renal disease.
Conclusion:
A modest association between CCB use and incident breast cancer was observed in the GP db, but results were not reproducible in the CV db. Given lack of a credible mechanism and failure of previous randomized CCB studies to detect a signal, we interpret these modest and conflicting associations to likely represent uncorrected confounding, e.g. prescriber bias or drug interactions. Similarly, we believe the results of Li et-al may represent confounding. Given the important role of CCBs in clinical medicine, further studies are warranted, including randomized trials to assess CCB safety with respect to breast cancer risk.
Calcium channel blockers and breast cancer incidence: An updated systematic review and meta-analysis of the evidence
