Angiotensin-Converting Enzyme Inhibitors, Calcium Channel Blockers, and Breast Cancer

Meier, Christoph; Derby, Laura E.; Jick, Susan S.; Jick, Hershel

doi:10.1001/archinte.160.3.349

Cited by 113 publications

(86 citation statements)

References 21 publications

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“…In a previous study our group found that diagnoses of cancer are validated in 95% of cases for whom further information is obtained from general practitioners (Jick et al, 1997). Thirty of 30 randomly selected probable cases of breast cancer were confirmed in an earlier review of their pathology report or hospital discharge summary (Meier et al, 2000). Also, we recently reported that the age-adjusted incidence rates of breast cancer among women in the GPRD are closely similar to those reported by the UK Office of National Statistics (Kaye et al, 2000).…”

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confidence: 59%

Statin use, hyperlipidaemia, and the risk of breast cancer

et al. 2002

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Hydroxymethyl glutaryl coenzyme A inhibitors ('statins') are carcinogenic in rodents and an increased incidence of breast cancer was reported among pravastatin users in one randomised trial. We conducted a case -control study in the General Practice Research Database to evaluate the risk of breast cancer among 50-to 79-year old women treated with statins for hyperlipidaemia. Case and control women were matched by age, general practice, duration of prescription history in the General Practice Research Database, and index date. Adjusting for history of benign breast disease, body mass index, and use of hormone replacement therapy, women currently treated with statins had an estimated relative risk for breast cancer of 1.0 (95% confidence interval 0.6 -1.6) compared to women without hyperlipidaemia. Untreated hyperlipidaemia was associated with an increased risk of breast cancer (estimated relative risk 1.6; 95% confidence interval 1.1 -2.5). The estimated relative risk among women currently receiving only non-statin lipid-lowering drugs was similar to that of women with untreated hyperlipidaemia (1.8; 95% confidence interval 0.9 -3.4). We found no evidence for an increasing trend in breast cancer risk with increasing duration of statin use (median duration 1.8 years, maximum 8.6 years). (Newman and Hulley, 1996). Clinical trials focused on cardiovascular mortality and morbidity have had limited ability to assess the human carcinogenic potential of statins due to relatively short follow-up. Among 13 trials reporting cancer incidence and deaths as outcomes, with an average follow-up time of 3.3 years, no evidence was found of an overall increased risk of cancer (relative risk (RR) 1.03, 95% confidence interval (CI) 0.90 -1.17) or cancer deaths (RR 0.95, 95% CI 0.74 -1.21) among statin users (Hebert et al, 1997). However, concern was raised by the only study that reported on breast cancer risk, with 12 cases among pravastatin users and only one case in a placebo group of similar size (P=0.002) (Sacks et al, 1996).We used the General Practice Research Database (GPRD), an automated data source containing drug prescription and other medical information on more than 3 million residents of the UK, to study the possible relation of breast cancer to statin use and hyperlipidaemia. MATERIALS AND METHODSWe conducted a matched case -control study on the risk of breast cancer in relation to use of statins, non-statin lipid-lowering agents, and untreated hyperlipidaemia among women aged 50 -79 diagnosed with breast cancer in 1992 -1998 in the UK General Practice Research Database (GPRD). General Practice Research Database (GPRD)The GPRD started in 1988 and has been used extensively for research studies; the subset of data we have used during the past decade is of consistently high quality. (Jick et al, 1991) Some 350 practices contributed to data used in this report. In a previous study our group found that diagnoses of cancer are validated in 95% of cases for whom further information is obtained from general practitioners (Jic...

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confidence: 59%

Statin use, hyperlipidaemia, and the risk of breast cancer

et al. 2002

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“…The risk estimate for diltiazem use was correspondingly increased, but nonsignificant [4,5,9,13]. On the other hand, five case-control studies [10,11,13,15,20] and several cohort studies [9,12,14,[21][22][23][24] and an analysis of verapamil use within a randomised controlled trial [25] suggested no association between CCBs and cancer. However, a major limitation of most of these studies is the exposure assessment at baseline without detailed information on continuous drug use [5,6,[8][9][10][11][12]14,[21][22][23].…”

Section: Antihypertensivesmentioning

confidence: 99%

“…This may have led to a misclassification of exposure. In addition, confounder adjustment was found to be insufficient in most of studies mentioned [8,22,24], also due to the limitations of registrations [9,15]. Continuous exposure to CCB with a drug prescription history of several years and detailed use pattern is needed to investigate the association with cancer and is provided in only a few studies [13,15,24].…”

Section: Antihypertensivesmentioning

confidence: 99%

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Verapamil is associated with an increased risk of cancer in the elderly: the Rotterdam study

Beiderbeck-Noll

Sturkenboom

Linden

et al. 2003

European Journal of Cancer

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The association between the use of calcium channel blockers (CCB) and cancer has received ample attention, but is still controversial. In this study, we have tested the hypothesis that the observed association between CCB and cancer in earlier studies could be explained by residual confounding or by misclassification of exposure because of the use of cross-sectional data on drug use. Data from the Rotterdam Study, a prospective population-based cohort study in the municipal area Ommoord, were used. The study population consisted of a cohort of 3204 participants aged 71 years or older who were followed from a baseline interview in the period 1991-1993 for the occurrence of incident cancer. Data on drug use were gathered at baseline and through the seven community pharmacies which served the Ommoord region during the study period between 1 January 1991 and 1 January 1999. Incident cancer events were gathered from a nationwide registry of hospitalisation data and from a specialised cancer centre in the Rotterdam region. We performed three analyses. First, we followed the method, and adjusted for the same risk factors, as in the earlier studies. In the second analysis, we included all risk factors that were univariately associated with cancer in the Rotterdam Study. In the third analysis, we included exposure to CCBs as time-varying co-variates, while adjusting for potential confounders. The relative risk (RR) of cancer associated with CCB was 1.4 (95% Confidence Interval (CI): 0.9-2.0) in the first analysis and lowered to 1.2 (95% CI: 0.8-1.8) upon adjustment for the different co-variates in the second. In both analyses, however, verapamil was significantly associated with cancer with RRs of 2.1 (95% CI: 1.1-4.0) and 2.0 (1.01-3.9), respectively, whereas no associations were found with the other CCB in this study, i.e. diltiazem and nifedipine. A significantly increased risk of cancer was found for intermediate daily doses of verapamil and diltiazem. Intake of other antihypertensives such as b-blocking agents, diuretics and ACE-inhibitors was not associated with cancer. In the third analysis with exposure to CCB as time-varying co-variates, the risk increase was non-significant for use of 2 years or less, 1.0 (95% CI: 0.7-1.5), and for use for a cumulative period of more than 2 years, 1.3 (95% CI: 0.8-2.0). However, in all models the hazard ratio was statistically significantly increased for verapamil, but not for diltiazem and nifedipine. On the basis of these analyses, we found no increase in cancer in users of diltiazem and nifedipine, nor in users of other antihypertensives. In line with earlier studies, however, we found an increased risk of cancer in users of verapamil. At variance with the conclusions from several other studies, we think that it is too early to conclude that CCB are not associated with cancer. #

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“…Comparison with a matched control group of 14 155 women did not support the hypothesis that use of ACE inhibitors affects the risk of malignancy. 54 Stahl et al 55 Likewise, in the population-based Prescription Database of North Jutland County and the Danish Cancer Registry, cancer incidence among 17 897 individuals prescribed ACEis did not confirm a protective effect of ACEi on the development of cancer. 56 In the Swedish trial STOP-Hypertension-2, comprising 6614 hypertensives, there were 625 new cases of cancer in 590 patients.…”

Section: Clinical Observationsmentioning

confidence: 96%

Angiotensin inhibition and malignancies: a review

Rosenthal

Gavras

2009

J Hum Hypertens

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After an early report that patients treated with angiotensin-converting enzyme (ACE) inhibitors had a lower than expected incidence of cancers, there was a large number of publications investigating the possible pathophysiological mechanism mediating this effect, as well as population studies comparing the incidence of cancers in patients treated with agents inhibiting the reninangiotensin system with their incidence in the general population. Several mechanisms are proposed to explain a potential anti-tumour activity of such agents in vitro in experimental animal models. However, the population studies are mostly inconclusive, although they do suggest a possible interaction between ACE genotypes and susceptibility to altered behaviour of certain tumours.

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Angiotensin-Converting Enzyme Inhibitors, Calcium Channel Blockers, and Breast Cancer

Abstract: The findings of this large case-control analysis do not support the hypothesis that longer-term use of ACE inhibitors or CCBs affects the risk of developing breast cancer.

Cited by 113 publications

References 21 publications

Statin use, hyperlipidaemia, and the risk of breast cancer

Statin use, hyperlipidaemia, and the risk of breast cancer

Verapamil is associated with an increased risk of cancer in the elderly: the Rotterdam study

Angiotensin inhibition and malignancies: a review

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