Table 3.

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

Study and countryYearsDesignCases/controlsExposure measurementMajor findingsConfoundersComments
Peeters et al. (52) Denmark1991-1994Registry-based study6 cases were identified using a population-based prescription database and the Danish Cancer RegistryEpidemiologic prescription databaseUse of statins vs none, standardized incidence ratio: 1.4 (0.5-3.1)
1,882 patients in cohort, with 4,580 person-years of follow-up
Jick et al. (46) Quebec1988-1994Registry-based studyCases: 56 breast cancer cases were identified using computerized health databases of the Regie de l'Assurance-Maladie du QuebecComputerized health record databaseEver used statin vs use of bile acid binding resins: 0.67 (0.33-1.38)Age at index date, previous neoplasm, year of cohort entry, use of fibric acid, use of other lipid-reducing agents, and a comorbidity score
Controls: 560 cancer-free controls matched to cases (6,721 patients in cohort)
Michels et al. (51) UK1992-1998Registry-based studyCases: 224 incident invasive and in situ carcinomas from the General Practice Research DatabaseGeneral practice database/electronic medical recordCurrent statin use vs none: 1.0 (0.6-1.6)
Controls: 1,009 cancer-free matched controlsPast statin use vs none: 1.3 (0.6-2.8)
Statin use >5 y vs none: 1.1 (0.4-3.0)
Li et al. (80) USA1987-2001Hospital-based case-control studyCases: 1,132 primary invasive and in situ breast cancer confirmed by pathology reportIn-person interviewFor all breast cancers, use of statins ≥ 3 y vs none: 2.1 (1.1-4.0)Age, year of interview, study center, education, number of doctor visits two y before hospitalization, use of conjugated estrogens, HRT use, oral contraceptive use, religion, race, alcohol consumption, and BMI
Controls: 589 women with noncancer, non-statin-related conditionsFor carcinoma in situ, use of statins ≥3 y vs none: 3.4 (1.5-8.0)
For invasive breast cancer, use of statins ≥3 y vs none: 1.5 (0.7-3.1)
Alshafie et al. (87) USA1992-2001Cohort study244 incident breast cancer cases confirmed by medical record and pathology reportQuestionnaire and interviewsEver used statins vs none: 0.28 (0.09-0.86)Age and body weightAdjustment for following variables did not appreciably effect risk estimates: HRT use, family history of breast cancer, mammography use, height, education, health status, age at menarche, age at first birth, parity, physical activity, and alcohol consumption
7,284 cancer-free cohort membersEver used nonstatin lipid-lowering drug vs none: 0.37 (0.14-0.99)
Ever used any lipid-lowering drug vs none: 0.32 (0.15-0.68)
Gonzalez-Perez et al. (45) Canada1989-1997Registry-based study879 incidence breast cancers identified through regional cancer registryComputerized health record databaseEver used statins vs none: 1.09 (0.93-1.28)None
Cancer-free cohort members (total cohort = 67,472)Age ≤55 y and ever used statins vs none: 0.81 (0.53-1.24)
Age >55 y and ever used statins vs none: 1.15 (0.97-1.37)
Age >55 and ≥37 y HRT use vs none: 2.04 (1.20-3.46)
Boudreau et al. (56) USA1997-1999Population-based case-control studyCases: 975 primary, invasive cancers identified via tumor registry/Surveillance, Epidemiology and End ResultsIn-person interviewEver used statins vs none: 0.9 (0.7-1.2)Age, reference year, county of residence, use of antihypertensive medication
Controls: 1,007 cancer-free general population controls identified via Medicare/Medicaid listsCurrent statin use >5 y vs none: 0.7 (0.4-1.0)
Kaye and Jick (126) UK1990-2002Registry-based studyCases: 3,224 incident cancer cases, including 698 breast cancers from the General Practice Research DatabaseGeneral practice database/electronic medical record, self-administered questionnaireCurrent statin use vs none: 0.9 (0.6-1.3)Not specified for breast model, but considered BMI, smoking status, average general practice visit frequency during follow-up
Controls: 14,844 cancer-free matched controls
Graaf et al. (127) The Netherlands1991-1998Registry-based studyCases: 3,129 incident cancer cases, including 467 breast cancers from the PHARMO drug dispensing database systemDrug dispensing database linked to hospital discharge recordEver statin use vs none: 1.07 (0.65-1.74)Diabetes mellitus, prior hospitalizations, chronic disease score, chronic use of diuretics, ACEi, CCB, hormones, NSAID, and other lipid-lowering therapy
Controls: 16,976 cancer-free matched controls
Olsen et al. (48) Denmark1989-2002Registry-based studyCases: 22,512 incident cancer cases, including 3,141 breast cancer cases identified via Central Population Register, Epidemiologic Prescription Database, and Danish Cancer RegistryEpidemiologic prescription databaseEver statin use vs none: 1.02 (0.76-1.36)Age, calendar period, NSAID, HRT, cardiovascular drugs
Controls: 334,754 men and women in general population, with 12,251 statin users
Brueggemeier et al. (85) USA1994-2000Cohort studyCases: 3,177 incident cases of breast cancer identified from self-report and medical record reviewSelf-administered questionnaireCurrent statin use vs none: 0.91 (0.76-1.08)Age, age at menarche, parity and age at first birth, height, BMI, first-degree family history of breast cancer, benign breast disease, alcohol consumption, physical activity, menopausal status, age at menopause and HRT use
Controls: 75,828 selected cohort members with complete statin use informationStatin use for <2 y vs none: 0.86 (0.68-1.08), statin use for 2-4 y vs none: 0.99 (0.75-1.31), and statin use for >4 y vs none: 0.93 (0.60-1.44)
Dale et al. (61) USAN/AMeta-analysisN/ALiterature database search through July 2005 of randomized clinical trials5 studies of breast cancer incidence representing 145 casesN/A
27 of 8,943 potential articles were analyzed, representing 86,936 participantsStatin use vs none: 1.33 (0.79-2.26)
Bonovas et al. (60) N/AN/AMeta-analysisN/ALiterature database search through March 2005 of randomized clinical trials or observational studiesStatin use vs none, in fixed effects model: 1.03 (0.93-1.14)N/A
16 of 683 potential articles were analyzedStatin use vs none, in random effects model: 1.02 (0.89-1.18)
Hwang et al. (86) USA1993-2004Cohort studyCases: 4,383 incident cases of self-reported breast cancer confirmed by medical record and pathology reviewIn-person interview, medical record dataStatin use vs none: 0.91 (0.80-1.05)Age, BMI, race, smoking, family history of breast cancer, education, hysterectomy, mammogram in the last 2 y, age at menarche, parity/age at first birth, alcohol use, percentage of calories from fat, physical activity, and NSAID use
Controls: 156,351 cohort membersHydrophobic statins (Zocor, Mevacor, or Pravachol) vs none: 0.82 (0.70-0.97)
Risk did no vary significantly by dose, duration, and HRT use at baseline
Tumor characteristics were similar across statin users and nonusers
Setoguchi et al. (91) USA1994-2003Registry-based studyCohort of 31,723 adults with initiation of statin use (24,439) or glaucoma medication use (7,284)Epidemiologic prescription databaseStatin use vs glaucoma medication use: 0.99 (0.74-1.33)Age, sex, race, Charlson comorbidity score, physician visits, total medications used, hospitalizations, prior nursing home stay, mammography, gynecologic examination, colonoscopy, fecal occult blood testing, osteoporosis drug use, arthritis, diabetes, inflammatory bowel disease, benign breast disease, HRT use, NSAID use, gastroprotective drug use, obesity, tobacco abuse
Cases: 268 individuals with primary invasive breast cancer
Boudreau et al. (92) USA1990-2004Registry-based studyCohort of 92,788 women ages 45-89 in a large health planInsurance plan prescription databaseStatin use ever vs never: 1.07 (0.88-1.29)Age, HRT use, diabetes, use of other lipid-lowering drugs, BMI
2,707 incidence invasive breast cancer cases identified through Surveillance, Epidemiology and End ResultsDuration ≥5 y: 1.27 (0.89-1.81)
Ever statin use among ER+: 1.06 (0.85-1.32)
Duration ≥5 y among ER+: 1.24 (0.83-1.86)
Ever statin use among ER-: 1.28 (0.78-2.08)
Duration ≥5 y among ER-: 1.81 (0.75-4.36)
Coogan et al. (55) USA1991-2005Hospital-based case-control studyCases: 1,185 women with incident invasive breast cancer admitted to a participating hospitalIn-person interviewRegular statin use vs never use: 1.2 (0.8-1.8)Age, interview year, study center, BMI, alcohol consumption, race, education, tobacco use, NSAID use, HRT use, oral contraceptive use, menopausal status, parity, age at menarche, family history of breast cancer, religion
Controls: 2,081 women admitted to a participating hospital without cancer or disorders related to statin useStatin use duration ≥5 y: 1.5 (0.7-3.2)