Some Antihypertensives Linked to Breast Cancer Risk

Janis C. Kelly

August 05, 2013

The first observational study of long-term antihypertensive use and breast cancer risk has found that calcium-channel blockers are associated with a more than 2-fold increased risk and that angiotensin-converting-enzyme (ACE) inhibitors are associated with a reduced risk.

These findings come from a study published online August 5 in JAMA Internal Medicine.

Women who had taken calcium-channel blockers for 10 years or more had more than double the usual risk for invasive ductal breast carcinoma (IDC) (odds ratio [OR], 2.4) and for invasive lobular breast carcinoma (ILC) (OR, 2.6). The researchers also observed a possible association between the long-term use of ACE inhibitors and reduced risks for both IDC (OR, 0.7) and ILC (OR, 0.6), although the risk estimate for IDC was within the limits of chance.

No Changes in Clinical Practice Recommended Yet

"We don't think 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 relation at this point," lead author Christopher Li, MD, PhD, from the Fred Hutchinson Cancer Research Center in Seattle, told Medscape Medical News.

Dr. Li and colleagues interviewed women 55 to 74 years of age from the Puget Sound region — 880 with IDC, 1027 with ILC, and 856 without cancer (control group). Participants were interviewed in person to establish detailed histories of hypertension and heart disease and risk factors for cancer, including family history, obesity, smoking, and alcohol use. The researchers gathered data on the use of antihypertensive drugs, including beginning and end dates of use, drug names, dose, route of administration, pattern of use, and indication.

The antihypertensives included ACE inhibitors, angiotensin-receptor blockers, beta blockers, calcium-channel blockers, diuretics, and combination antihypertensive preparations, regardless of indication.

Calcium-channel blockers are among the most frequently prescribed medications in the United States; they accounted for nearly 98 million of the more than 678 million prescriptions filled in 2010.

Subjects who had used antihypertensives for 6 months or longer and were still using them were classified as current users, subjects who had used them for 6 months but were no longer using them were classified as former users, and subjects who had used them for less than 6 months were classified as short-term users.

In the regression analyses, potential confounders included age, county of residence, other commonly used medications, comorbid conditions (cardiovascular disease, diabetes, hyperlipidemia, depression), alcohol use, and estrogen-receptor status.

Increased Risk After 10 Years

"In examining duration effects for current users, we found an increased risk only in relation to the use of calcium-channel blockers for 10 years or longer, and an increased risk was observed for both IDC (OR, 2.4; 95% confidence interval [CI], 1.2 - 4.9; P = .04 for trend) and ILC (OR, 2.6; 95% CI, 1.3 - 5.3; P = .01 for trend). This association with 10 years or longer of current calcium-channel blocker use did not vary appreciably when results were further stratified by estrogen-receptor status," the researchers report.

Dr. Li told Medscape Medical News that they were surprised by the magnitude of the risk associated with calcium-channel blockers 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," Dr. 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."

The mechanism behind the apparent calcium-channel blocker effect is not known, Dr. Li explained, but some researchers suspect that these drugs might increase cancer risk by inhibiting apoptosis.

"First-Rate Study," But Confirmation Needed

"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 SEER surveillance system, had a high (80%) case response rate, and used best practices in ascertaining medication use from study participants," Patricia F. Coogan, ScD, from the Slone Epidemiology Center at Boston University, writes in a related commentary.

"Given these results, should the use of calcium-channel blockers 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," Dr. Coogan explains.

"If the 2- to 3-fold increase in risk found in this study is confirmed, long-term calcium-channel blocker 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," Dr. Coogan notes.

"We are cautious and don't want to read too much into this, since this was the first study to look at long-term use of these medications. We need to see confirmation of the study before making any clinical recommendations," Dr. Li emphasized.

The National Cancer Institute funded the study. Dr. Li, his coauthors, and Dr. Coogan have disclosed no relevant financial relationships.

JAMA Intern Med. Published online August 5, 2013. Abstract, Commentary

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