Table 4.

Epidemiologic studies of the role of antihypertensive drug use in breast cancer development

Study and countryYearsDesignCases/controlsExposure measurementMajor findingsConfoundersComments
Schreinemachers and Everson (110) UK1995Registry-based studyCases: 80 cases of invasive breast cancer identified from General Practice ResearchGeneral practice database/electronic medical record, self-administered questionnaireEver used CCB vs β-blocker users: 1.32 (0.72-2.41)Smoking, BMI, change of medication, duration of hypertension, diuretic use
Database
Controls: 1,750 total cancer-free controls frequency matched by age and practice location
Egan et al. (117) USA1989-1996Cohort study75 primary invasive cases confirmed by medical record abstractionStandardized questionnaireEver used CCB vs none: 2.57 (1.47-4.49)Age, race, parity, age at menopause, self-reported diabetes
3,123 cancer-free cohort membersEver used β-blocker vs none: 1.14 (0.58-2.25)
Ever used ACEi vs none: 0.93 (0.37-2.34)
Ever used any diuretic vs none: 1.38 (0.83-2.29)
Ever used any vasodilator vs none: 0.30 (0.07-1.21)
Olsen et al. (48) Denmark1991-1993Registry-based study32 primary invasive cases identified by population-based Epidemiologic Prescription Database and confirmed via Danish Cancer RegistryEpidemiologic prescription databaseEver used CCB: standardized incidence ratio: 0.8 (0.5-1.1)None
17,911 patients in cohort, including men and women (32,540 person-years of follow-up)
Peeters et al. (52) The Netherlands1974-1985CohortCohort of 11,075 women ages 50-65 y enrolled in a breast cancer screening projectSelf-administered questionnairesNo increased in mortality from breast cancer for use of any antihypertensive drug (data not shown)
114 cases of breast cancer identified
Jacobs et al. (115) USA1988-1994Cohort study355 self-reported cancers confirmed by medical record abstractionSelf-administered questionnaireUse of CCB vs none: 1.07 (0.78-1.48)Age, multiple drug use, self-reported weight, height, smoking status and mean number of cigarettes smoked per day among women who smoked in 1988, alcohol intake in 1988, physical activity, menopausal status in 1988, postmenopausal HRT use, cholesterol level, systolic and diastolic blood pressure in 1988, aspirin intake, diabetes, history of stroke, myocardial infarction, CABG/PTCA, angina, hypertension in or before 1988, family history of breast cancer, history of benign breast disease, age at menarche, parity, age at first birth, age at menopause
18,635 cohort members in analysis (107,256 person-years of follow-up)
Ready et al. (114) USA1983-1996Hospital-based case-control studyCases: 2,893 primary breast cancer cases confirmed from discharge summaries and pathology reportsIn-person interviewUse of CCB ≥5 y vs none: 1.1 (0.7-1.8)Age, study center, interview year, BMI, annual visits to physician before diagnosis, race, years of education, breast cancer in mother or sister, benign breast disease, age at menarche, age at first birth, parity, age at menopause, alcohol consumption, duration of oral contraceptive use, duration of HRT use
Controls: 6,492 controls admitted for nonmalignant conditionsUse of β-blockers ≥5 y vs none: 1.1 (0.9-1.5)
Use of ACEi ≥5 y vs none: 1.2 (0.7-2.2)
Harris et al. (113) Denmark1989-1995Registry-based study84 primary invasive cases identified by population-based Epidemiologic Prescription Database and confirmed via Danish Cancer RegistryEpidemiologic prescription databaseEver used CCB: standardized incidence ratio: 0.97 (0.77-1.20)None
23,167 cohort members, including men and women (73,193 person-years follow-up)
Johnson et al. (111) UK1992-1997Registry-based studyCases: 3,706 cases of invasive breast cancer identified from General Practice ResearchGeneral practice database/electronic medical recordACEi use ≥5 y vs none: 1.0 (0.7-1.5)BMI, smoking statusAdjustment for following variables did not appreciably effect risk estimates: alcoholism, hysterectomy, and breast lumps
DatabaseCCB use ≥5 y vs none: 0.9 (0.7-1.2)
Controls: 14,155 cancer-free controls from cohort matched 4:1 to cases on age, physician practice, index date, number of years of medical history record in databaseβ-blocker use ≥5 y vs none: 1.0 (0.8-1.2)
Gallicchio et al. (107) Denmark1989-1995Registry-based study83 primary invasive cases identified by population-based Epidemiologic Prescription Database and confirmed via Danish Cancer RegistryEpidemiologic prescription databaseEver used ACEi (with previous use of CCB and/or β-blocker): standardized incidence ratio: 1.1 (0.9-1.3)None
17,897 cohort members, including men and women (66,827 person-years follow-up)Exclusive ACEi use: standardized incidence ratio: 1.1 (0.8-1.5)
Shen et al. (109) UK1995-2001Registry-based studyCases: 3,708 cases of invasive breast cancer identified from General Practice ResearchGeneral practice database/electronic medical recordUsed diuretics > 3 y vs none: 1.1 (0.9-1.2)Age, calendar year, hypertension, BMI, alcohol intake, smoking status, HRT use, and prior breast lump and/or breast biopsy
DatabaseUsed β-blockers > 3 y vs none: 1.1 (0.9-1.2)
Controls: 20,000 cancer-free controls from cohort matched to cases on age and calendar year (study cohort = 734,899 women)Used ACEi > 3 y vs none: 0.9 (0.7-1.2)
Used CCB >3 y vs none: 1.0 (0.8-1.2)
Used α-blockers >3 y vs none: 0.2 (0.2-1.3)
Friis et al. (82) USA1997-1999Population-based case-control studyCases: 975 cases of invasive breast cancer identified via Cancer Surveillance System, a population-based cancer registryIn person interviewUsed CCB for 15 y vs none: 0.6 (0.3-1.3)Reference ageAdjustment for following variables did not appreciably effect risk estimates: race, income, marital status, education, age at menarche, parity, age at first birth, type of menopause, age at menopause, duration of oral contraceptive use, HRT use, first-degree family history of breast cancer, smoking status, average daily alcohol intake, and BMI
Controls: 1,007 cancer-free controls identified from list of Medicare/Medicaid recipients, selected for similar ageUsed β-blockers for ≥15 y vs none: 2.1 (1.2-3.7)
Used ACEi for ≥15 y vs none: 0.8 (0.4-1.6)
Used diuretics for ≥15 y vs none: 1.2 (0.8-1.6)
Moorman et al. (108) Denmark1990-2002Registry-based study264 primary invasive cases identified by population-based Epidemiologic Prescription Database and confirmed via Danish Cancer RegistryEpidemiologic prescription databaseEver used any antihypertensive vs never: 0.95 (0.81-1.10)Age, calendar period, HRT use, NSAID use, parity, and age at first birth
49,950 women in total cohort (19,284 statin users contributing 109,985 person-years of follow-up)Ever used ace inhibitor vs none: 0.99 (0.75-1.31)
Ever used angiotensin II agonist vs none: 1.01 (0.67-1.51)
Ever used β-blockers vs none: 0.98 (0.79-1.22)
Ever used CCB vs none: 0.80 (0.59-1.09)
Ever used diuretic vs none: 0.95 (0.8-1.12)
Risk estimates not significantly effected by number of prescriptions, years of follow-up, type of diuretic, or type of calcium antagonist
Largent et al. (81) USA1994-1995Population-based case-control studyCases: 523 women age 50-75 y with incident breast cancerSelf-administered questionnaireDiuretic use ever vs never: 1.79 (1.07-3.01)Age, BMI, diabetes, smoking, alcohol use, menopausal status, family history of breast or ovarian cancer, age at first pregnancy, education
Controls: 131 women ages 50-75 y old identified through random-digit dialing, matched to cases on ageDiuretic duration ≥6 y vs never: 3.50 (1.64-7.50)
Use of nondiuretic antihypertensive drug ever vs never: 1.18 (0.69-2.03)
Nondiuretic antihypertensive duration ≥6 y vs never: 1.24 (0.62-2.50)