Some antihypertensives linked to breast-cancer risk
AUGUST 5, 2013
AUGUST 5, 2013
Boston, MA - The first observational study of long-term antihypertensive use and breast-cancer risk found that calcium-channel blockers (CCBs) were associated with a more than twofold increased risk, while ACE inhibitors appeared to be associated with a reduced risk. The new findings are published online August 5, 2013 in JAMA Internal Medicine [1].
Women who had taken CCBs for 10 years or more had more than double the usual risk for invasive ductal breast carcinoma (IDC) and for invasive lobular breast carcinoma (ILC). The researchers also observed a possible association between long-term use of ACE inhibitors and reduced risks of both IDC and ILC, although the IDC risk estimate was within the limits of chance.
No changes in clinical practice recommended yet
"We don't think that this should change clinical practice in any way. It was the first study of long-term antihypertensive use. It was an observational study, not a clinical trial. We can suggest an association, but we cannot infer any causal relationship at this point," lead author Dr Christopher Li (Fred Hutchinson Cancer Research Center, Seattle, WA) said in an interview.
Li and colleagues interviewed 1763 women (aged 55-74) from the Puget Sound region, including 880 with invasive ductal cancer, 1027 with invasive lobular cancer, and 856 cancer-free controls for medical histories, risk factors, and history of drug therapies.
Increased risk after 10 years
"In examining duration effects for current users, we found an increased risk only in relation to use of calcium-channel blockers for 10 years or longer, and an increased risk was observed for both IDC (OR 2.4, 95% CI 1.2-4.9; p=0.04 for trend) and ILC (OR 2.6, 95% CI 1.3-5.3; p=0.01 for trend). This association with 10 years or longer of current CCB use did not vary appreciably when results were further stratified by ER," the investigators reported. Their analysis controlled for age, county of residence, other commonly used medications, comorbid conditions (cardiovascular disease, diabetes, hyperlipidemia, depression), alcohol use, and estrogen-receptor (ER) status.
Li said that the researchers were surprised both by the magnitude of the risk associated with CCBs and by the decrease associated with ACE inhibitors.
"We expected that we might see some increase in breast-cancer risk with calcium-channel blockers, but not a more than doubling of the risk," Li said. "The suggestion of an association between ACE inhibitors and reduction in breast-cancer risk was a very unexpected finding and is worthy of follow-up."
Li said that the mechanism behind the apparent CCB effect is unknown but that some researchers suspect that these drugs might increase cancer risk by inhibiting apoptosis.
"First-rate study" but still needs confirmation
"The data are persuasive because this was a first-rate study: it was population-based, large (1900 case patients and 856 controls), identified cases from the Seattle-area [Surveillance, Epidemiology and End Results] SEER surveillance system, had a high (80%) case response rate, and used best practices in ascertaining medication use from study participants," Dr Patricia F Coogan (Boston University, MA) writes in a related commentary [2].
"Given these results, should the use of CCBs be discontinued once a patient has taken them for 9.9 years? The answer is no, because these data are from an observational study, which cannot prove causality and by itself cannot make a case for change in clinical practice," Coogan said.
"If the two- to threefold 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. Thus, it is important that efforts be made to replicate the findings," Coogan said.
| The National Cancer Institute funded the study. Li and coauthors reported no conflicts of interest. Coogan reported no relevant financial interests. |
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