Table 1.

Epidemiologic studies of the role of antibiotics use in breast cancer development

Study and countryYearsDesignCases/controlsExposure measurementMajor findingsConfoundersComments
Danielson et al. (15) Finland1973-1991Cohort study157 cases in Finnish Mobile Clinic Health Examination Survey identified via Finnish Cancer RegistrySelf-report questionnaireHistory of use of antibacterial treatment of bacteriuria vs none: 1.31 (0.95-1.81)Age, region type, education, marital status, body mass index (BMI), parity, smoking, height, alcohol use, and screening positive for bacteriuria
9,304 cancer-free cohort members (total cohort 9,461)Women ages <50 y, 1.74 (1.13-2.68); women ages >50 y, 0.97 (0.59-1.58)
Lawlor et al. (14) USA1993-2001Population-based case-control studyCases: 2,266 women enrolled in large health plan with primary invasive breast cancer identified from Surveillance, Epidemiology and End ResultsSelf-report questionnaire, health plan databaseNo appreciable difference by menopausal status; therefore all analyses combinedAge, length of health plan enrollmentAdjustment for following variables did not appreciably affect risk estimates: age at reference date, education, race, number of annual health-care visits, pharmacy co-pay status, age at menarche, parity, age at firth birth >30 y, BMI, family history of breast cancer, high breast density, hysterectomy, menopausal status, age at menopause ≥50 y, oral contraceptive use, and postmenopausal hormone replacement therapy (HRT) use
Controls: 7,953 disease-free health plan members frequency matched 3:1 on age and sexHighest number of days antibiotic use (≥1,001) vs none: 2.07 (1.48-2.89)
Highest number of prescriptions filled (≥51) vs none: 2.31 (1.69-3.15)
Wang et al. (16) Denmark1994-2003Registry-based studyCases: 2,728 incident cases identified via population Hospital Discharge RegistryEpidemiologic prescription databaseHighest number of prescriptions for antibiotics (>10) vs none: 1.00 (0.86-1.15)Full sample: HRT use
Controls: 27,280 controls from population-based Civil Registration System matched 10:1 to casesIn women ages <70 y: 1.11 (0.93-1.32)Women ages <70 y; HRT use, age at first birth, and parity
Weiss et al. (18) UK1995-2001Registry-based studyCases: 3,708 cases identified from General Practice Research DatabaseGeneral practice database/electronic medical recordHighest number of days of antibiotic use (≥501) vs none: 1.2 (0.9-1.6)Age, calendar year, BMI, alcohol intake, HRT use, NSAID use, prior benign breast disease, utilization of health services, time under observation
Controls: 20,000 frequency matched cancer-free controlsBy indication vs none: respiratory infection 0.8 (0.7-1.0), urinary tract infection 0.9 (0.6-1.2), skin infection 1.2 (0.9-1.6), other infection 1.0 (0.8-1.3)
Kaye and Jick (124) UK1987-2002Registry-based studyCases: 1,268 cases identified from those with 6 y recorded medical history in General Practice Research DatabaseGeneral practice database/electronic medical recordHighest number of days of use (≥501) vs none: 1.2 (0.6-2.4)Risk estimates not appreciably changed when adjusted for following covariates: BMI, HRT use, history of benign proliferative breast disease, frequency of mammograms, frequency of visits to general practice
Controls: 6,291 cancer-free controls matched to cases up to 5:1
Didham et al. (125) New Zealand1998-2002Registry-based studyCases: 700 cases (including 5 males) identified from General Practitioner Research DatabaseGeneral practice database/electronic medical recordEver prescription for any antibiotic vs none: 1.02 (1.0-1.05)NoneAnalysis includes male breast cancers analyzed risk using conditional logistic regression
Controls: 700 cancer-free controls matched 1:1 to cases on age, sex, semesters of available dataEver penicillin vs none: 1.07 (1.02-1.13)
Ever macrolide vs none: 0.90 (0.81-0.99)
Ever tetracycline vs none: 1.06 (0.97-1.17)
Velicer et al. (13) USA1993-2001Case only2,266 women with primary invasive breast cancer enrolled in Group Health Cooperative and identified through Surveillance, Epidemiology and End ResultsInsurance plan prescription database and cost/utilization records, self-reported questionnaireAntibiotic use ≥101 d vs none was not associated with tumor stage, grade, histology, or ER statusAge, length of enrollmentAll OR >1: authors interpret as possible increase in less favorable tumor characteristics with antibiotic use
Regional/distant vs local stage: 1.30 (0.93-1.81)
Grade 4 vs 1: 1.39 (0.47-4.16)
ER- vs ER+: 1.17 (0.79-1.75)
Lobular vs ductal histology: 1.24 (0.79-1.96)
Friedman et al. (12) USA1994-2003Registry-based studyCohort: 2,130,829 female adult health subscribersInsurance plan prescription database, subscriber surveys, medical record reviewAny antibiotic use vs never 1.14 (1.10-1.18)Hormone use
Cases: 18,521 women with incident invasive breast cancerUse >1,000 d vs none: 1.17 (0.97-1.42)
Use >100 d
Tetracyclines: 1.23 (1.11-1.36), tetracyclines (excluding ever used macrolides): 1.14 (0.99-1.31)
Macrolides: 1.16 (0.98-1.36), macrolides (excluding ever used tetracycline): 1.18 (0.93-1.49)
Penicillin: 1.03 (0.94-1.13)