Long-term use of CCBs may increase risk of breast cancer

Long-term use of calcium-channel blockers (CCBs) may increase the risk of breast cancer in postmenopausal women, but additional research is needed to confirm, according to a study in JAMA Internal Medicine, published online August 5.

Results of 12 previous studies were inconsistent in terms of a positive association of CCB use and breast cancer risk, noted Christopher I. Li, MD, PhD, and colleagues from the Fred Hutchinson Cancer Research Center in Seattle, Wash.

“Four studies found that use of calcium-channel blockers or diuretics is positively associated with breast cancer risk, but eight studies reported no associations. However, in those studies finding no association, few investigated more than one class of antihypertensive or duration of use,” said Dr. Li and colleagues in the study.

The goal of the study was to assess the major classes of antihypertensive agents and any associated risk of the most common histologic forms of breast cancer: invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) in postmenopausal women who had used these drugs long-term.

Patients were eligible for inclusion if they were between 55 and 74 years of age and had been diagnosed with primary invasive breast cancer between January 2000 and December 2008. They lived in the Greater Seattle metropolitan area and had no prior history of cancer. Almost 2,500 case patients were identified and 80% were interviewed. Of these, 1,068 had ILC and 916 had IDC. There were 1,313 eligible controls, and 69% were interviewed. The final sample for analysis included 1,055 ILC cases, 905 IDC cases, and 891 controls.

Both case patients and controls were interviewed at their homes to determine medical histories that included hypertension, heart disease, and use of ACE inhibitors, angiotensin receptor blockers, beta-blockers, CCBs, diuretics, and combination antihypertensive medications. They were also asked about breast cancer risk factors, including family histories, lifestyle habits, and demographic characteristics.

Among current users the researchers found an increased risk of breast cancer only for those who used CCBs for 10 years or more. In the IDC cases, the odds ratio was 2.4 (95% CI, 1.2-49)(P=.04). Among ILC cases, the OR was 2.6 (95% CI, 1.3-5.3) (P=.01 for trend). The results for CCB users did not vary considerably for individuals with positive estrogen receptor status.

They also found that use of ACE inhibitors over the long term was associated with reduced risks of IDC and ILC, “though the risk estimate for IDC was within the limits of chance,” Dr. Li and colleagues said. “No statistically significant associations were seen for the other drug categories examined.”

Higher risks with short-acting CCBs

Risks may be higher for current CCB users of the short-acting formulations, the authors noted.

“Current users of short-acting calcium-channel blockers had a 3.7-fold increased risk of IDC and a similar 3.6-fold increased risk of ILC. However, because of the infrequency of duration of use of short-acting preparations, the effect of duration of use could not be assessed,” Dr. Li and colleagues noted.

There was not a related risk of IDC or ILC for patients who were current users of long-acting calcium-channel blockers, but for long-term use of 10 years or more, there was an elevated risk, they said.

“Current use of non-dihydropyridines for any duration was associated with a 60% increased risk of both IDC and ILC, but only current use of dihydropyridines for 10 years or longer was associated with elevated risks of IDC and ILC,” the authors said.