Calcium channel blockers and breast cancer: an important risk factor discovered?

A report in JAMA - Internal Medicine^[1] raises important safety concerns about calcium channel blockers, one of the most widely prescribed classes of antihypertensives used world-wide.

In the population-based case-control study by Li et al, participants in the 3-county Seattle–Puget Sound metropolitan area were women aged 55 to 74 years, 880 of them with invasive ductal breast cancer, 1027 with invasive lobular breast cancer, and 856 with no cancer serving as controls. The exposures studied were recency and use of antihypertensive medications while the main outcome measures were risks of invasive ductal and invasive lobular breast cancers.

Current use of all types of calcium channel blockers (short-acting vs long-acting, dihydropyridines vs non-dihydropyridines) for 10 or more years was associated with higher risks of ductal breast cancer (odds ratio [OR], 2.4; 95% CI, 1.2-4.9) (P = .04 for trend) and lobular breast cancer (OR, 2.6; 95% CI, 1.3-5.3) (P = .01 for trend). Importantly, no other classes of antihypertensives evaluated (ACE inhibitors, ARBs, diuretics or beta blockers) showed added risk.

The study was the first of its kind to demonstrate this effect and presently the biologic mechanism is unknown. One theory suggests that interference with calcium transport in to cells inhibits apoptosis, an important common mechanism for tumor promotion among many cancers. This study demonstrates an association - not causality - and  many similar claims have been made for different antihypertenisve classes that ultimately failed to materialize upon further study. As an example, as reported on UKidney in 2010, ARBs were linked to lung cancer risk, an association that did not seem to manifest upon further review. And as hypertension expert Dr. Franz Messerli points out “there is virtually no antihypertensive drug or drug class that has not been associated with cancer at one time or another".^[2]

The current study by Li et al is however concerning. As one commentator pointed out, "if the 2- to 3-fold increase in risk found in this study is confirmed, long-term CCB use would take its place as one of the major modifiable risk factors for breast cancer".^[3]

Patients are encouraged to discuss these findings with their physicians before stopping any medications they have been prescribed.