The long-term use of calcium-channel blockers is associated with a doubling of the risk of both invasive ductal carcinoma and invasive lobular carcinoma of the breast, according to a report published online Aug. 5 in JAMA Internal Medicine.
This and other findings from a large population-based case-control study require confirmation in future research, because this is the first report of such a strong adverse long-term impact of calcium-channel blockers (CCBs) on breast cancer risk, said Dr. Christopher I. Li of the division of public health sciences, Fred Hutchinson Cancer Research Center, Seattle, and his associates.
The investigators found no such association between breast cancer and any of the other commonly used antihypertensive agents, even if they were taken for long durations.
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The study results are relevant to public health, given that antihypertensive drugs are the most commonly prescribed class of medication in the United States, the researchers noted.
Previous studies of a possible link between breast cancer risk on the one hand and antihypertensive agents in general, and CCBs in particular, on the other hand, have produced inconsistent results. Most have included relatively few cases of breast cancer, have not assessed longer durations of use, and have inadequately examined the more recently introduced forms of the drugs.
Dr. Li and his colleagues averted these drawbacks by assessing postmenopausal women who had taken all the major classes of antihypertensive drugs for long durations, in a large enough sample to include many cases of the two most common histologic subtypes of breast cancer: invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC).
They identified through a tumor registry 1,960 women aged 55-74 years who were diagnosed as having a primary IDC or ILC during January 2000 to December 2008 in the greater metropolitan Seattle area. These cases were matched for age and area of residence with 891 cancer-free women who served as controls. The two groups had similar annual household incomes and medical histories of hypertension, heart disease, and hypercholesterolemia.
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Overall use, current use, former use, and short-term use of antihypertensive drugs were not associated with the risk of either IDC or ILC.
Only the long-term use of calcium-channel blockers (10 years or more) was related to increased risk of breast cancer, with an OR of 2.4 for IDC and an OR of 2.6 for ILC, the investigators said (JAMA Intern. Med. 2013 Aug. 5 [doi:10.1001/jamainternmed.2013.9071]).
This association remained robust when the data were analyzed according to the tumor’s estrogen-receptor status: The ORs were 2.3 for ER-positive IDC, 3.1 for ER-negative IDC, and 2.6 for ER-positive ILC.
No other drug categories showed significant associations with breast cancer risk. “With respect to diuretic use, risks associated with thiazide and nonthiazide diuretic use were also assessed separately, but neither was associated with breast cancer risk,” they said.
A sensitivity analysis limited to women in both study groups who had hypertension and were currently using antihypertensive medications produced similar results. This indicates that the underlying condition itself does not explain the association with breast cancer, and thus confounding by indication was adequately controlled for.
“There was also some indication that current use of ACE inhibitors for 10 years or longer was associated with reduced risks of both IDC (OR, 0.7) and ILC (OR, 0.6), though the risk estimate for IDC was within the limits of chance,” they said.
This finding must be interpreted with caution and requires confirmation in future research that includes a large number of long-term users of ACE inhibitors, Dr. Li and his associates added.
The U.S. National Cancer Institute and the U.S. Department of Defense supported the study. No relevant financial conflicts of interest were reported.
Commentary – Stop prescribing CCBs?
Dr. Patricia F. Coogan comments: The use of CCBs should not be discontinued on the basis of this study because it is observational, it cannot prove causality, and its findings alone should not change clinical practice, said Patricia F. Coogan, Sc.D.
But neither should the findings be dismissed. “The data are persuasive because this was a first-rate study,” with a large sample, a high case response rate (80%), and best-practice ascertainment of medication use among the participants. “The study particularly excels in the careful analytic efforts used to identify alternate explanations for the findings,” and in ruling out confounding by indication.
If future research confirms the two- to threefold increase in breast cancer risk with long-term use of CCBs – the ninth most commonly prescribed class of drugs in the United States in 2009 – avoiding these medications will become one of the major modifiable risk factors for breast cancer, she said.
Dr. Coogan is at Slone Epidemiology Center at Boston University. She reported no financial conflicts of interest. These remarks were taken from her invited commentary accompanying Dr. Li’s report (JAMA Intern. Med. 2013 Aug. 5 [doi:10.1001/jamainternmed.2013.9069]).
