Epidemiologic studies of the role of statin drug use in breast cancer development
Study and country | Years | Design | Cases/controls | Exposure measurement | Major findings | Confounders | Comments |
---|---|---|---|---|---|---|---|
Peeters et al. (52) Denmark | 1991-1994 | Registry-based study | 6 cases were identified using a population-based prescription database and the Danish Cancer Registry | Epidemiologic prescription database | Use 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) Quebec | 1988-1994 | Registry-based study | Cases: 56 breast cancer cases were identified using computerized health databases of the Regie de l'Assurance-Maladie du Quebec | Computerized health record database | Ever 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) UK | 1992-1998 | Registry-based study | Cases: 224 incident invasive and in situ carcinomas from the General Practice Research Database | General practice database/electronic medical record | Current statin use vs none: 1.0 (0.6-1.6) | ||
Controls: 1,009 cancer-free matched controls | Past 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) USA | 1987-2001 | Hospital-based case-control study | Cases: 1,132 primary invasive and in situ breast cancer confirmed by pathology report | In-person interview | For 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 conditions | For 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) USA | 1992-2001 | Cohort study | 244 incident breast cancer cases confirmed by medical record and pathology report | Questionnaire and interviews | Ever used statins vs none: 0.28 (0.09-0.86) | Age and body weight | Adjustment 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 members | Ever 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) Canada | 1989-1997 | Registry-based study | 879 incidence breast cancers identified through regional cancer registry | Computerized health record database | Ever 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) USA | 1997-1999 | Population-based case-control study | Cases: 975 primary, invasive cancers identified via tumor registry/Surveillance, Epidemiology and End Results | In-person interview | Ever 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 lists | Current statin use >5 y vs none: 0.7 (0.4-1.0) | ||||||
Kaye and Jick (126) UK | 1990-2002 | Registry-based study | Cases: 3,224 incident cancer cases, including 698 breast cancers from the General Practice Research Database | General practice database/electronic medical record, self-administered questionnaire | Current 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 Netherlands | 1991-1998 | Registry-based study | Cases: 3,129 incident cancer cases, including 467 breast cancers from the PHARMO drug dispensing database system | Drug dispensing database linked to hospital discharge record | Ever 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) Denmark | 1989-2002 | Registry-based study | Cases: 22,512 incident cancer cases, including 3,141 breast cancer cases identified via Central Population Register, Epidemiologic Prescription Database, and Danish Cancer Registry | Epidemiologic prescription database | Ever 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) USA | 1994-2000 | Cohort study | Cases: 3,177 incident cases of breast cancer identified from self-report and medical record review | Self-administered questionnaire | Current 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 information | Statin 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) USA | N/A | Meta-analysis | N/A | Literature database search through July 2005 of randomized clinical trials | 5 studies of breast cancer incidence representing 145 cases | N/A | |
27 of 8,943 potential articles were analyzed, representing 86,936 participants | Statin use vs none: 1.33 (0.79-2.26) | ||||||
Bonovas et al. (60) N/A | N/A | Meta-analysis | N/A | Literature database search through March 2005 of randomized clinical trials or observational studies | Statin use vs none, in fixed effects model: 1.03 (0.93-1.14) | N/A | |
16 of 683 potential articles were analyzed | Statin use vs none, in random effects model: 1.02 (0.89-1.18) | ||||||
Hwang et al. (86) USA | 1993-2004 | Cohort study | Cases: 4,383 incident cases of self-reported breast cancer confirmed by medical record and pathology review | In-person interview, medical record data | Statin 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 members | Hydrophobic 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) USA | 1994-2003 | Registry-based study | Cohort of 31,723 adults with initiation of statin use (24,439) or glaucoma medication use (7,284) | Epidemiologic prescription database | Statin 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) USA | 1990-2004 | Registry-based study | Cohort of 92,788 women ages 45-89 in a large health plan | Insurance plan prescription database | Statin 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 Results | Duration ≥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) USA | 1991-2005 | Hospital-based case-control study | Cases: 1,185 women with incident invasive breast cancer admitted to a participating hospital | In-person interview | Regular 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 use | Statin use duration ≥5 y: 1.5 (0.7-3.2) |