Table 2.

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

Study and countryYearsDesignCases/controlsExposure measurementMajor findingsConfoundersComments
Weiss et al. (18) USA1988-1994Registry-based studyCases: 95 cancer recurrences or 78 second primary cancer cases among adults with past history breast, colon, or melanomaInsurance plan prescription databaseEver antidepressant use vs none and cancer recurrence: 0.97 (0.52-1.78)Older study but not listed as reviewed by Lawler et al.
Controls: matched 5:1 on age, sex, original cancer type from a cohort of 1,467 patientsEver antidepressant use vs none and second primary tumor: 0.94 (0.50-1.77)Nest case-control design but no information given specifically about controls, only about entire cohort
Sharpe et al. (22) Canada1981-1995Registry-based studyCases: 5,882 women with incident invasive breast cancerEpidemiologic prescription databaseHighest daily dose tricyclic antidepressant vs no use after 11-15 y: 2.02 (1.34-3.04)Age, index date, tricyclic antidepressant use in other periodsGenotoxic tricyclic antidepressants: amoxapine, clomipramine, desipramine, doxepin, imipramine, trimipramine
Controls: 23,517 women matched on age and sampling timeGenotoxic tricyclic antidepressants: 2.47 (1.37-4.40), nongenotoxic tricyclic antidepressants: 0.99 (0.49-1.99)Nongenotoxic tricyclic antidepressants: amitryptyline, maprotiline, nortryptyline, protryptyline
Highest duration of use (71-100% of 11-15 y)
Genotoxic tricyclic antidepressants: 2.39 (1.30-4.39), nongenotoxic tricyclic antidepressants: 1.02 (0.56-1.86)
Moorman et al. (19) USA1996-2000Population-based case-control studyCases: 938 cases of invasive breast cancer identified via a rapid case ascertainment systemIn-person interviewsAny antidepressant use vs none: 1.0 (0.7-1.2)Age and raceAdjustment for following variables did not appreciably effect risk estimates: age at menarche, menopausal status, family history of breast cancer in a first-degree relative, oral contraceptive use, HRT use, educational level, BMI, waist-to-hip ratio, alcohol consumption, and cigarette smoking
Controls: 771 controls selected from DMV and Health Care Financing AdministrationAny antidepressant ≥ 60 mo vs none: 1.0 (0.5-1.7)
Tricyclic antidepressants ≥36 mo vs none: 0.7 (0.3-1.7)
SSRI ≥36 mo vs none: 2.2 (0.8-6.3)
Steingart et al. (36) Canada1996-1998Population-based case-control studyCases: 3,133 female cases identified by the Ontario Cancer RegistrySelf-administered questionnaireAny regular antidepressant use vs none: 1.17 (1.01-1.36)AgeAdjustment for following variables did not appreciably effect risk estimates: height, BMI, age at menarche, parity, age at menopause, oral contraceptive use, alcohol consumption, family history of breast cancer, and history of benign breast disease, clinical depression, or anxiety
Controls: 3,062 population controls matched on age and sexHighest duration of antidepressant use (≥9 y) vs none: 1.15 (0.78-1.69)
Any SSRI use vs none: 1.33 (1.07-1.66)
Sertraline: 1.58 (1.03-2.41)
Paroxetine: 1.55 (1.00-2.40)
Fluoxetine: 1.09 (0.81-1.49)
Any tricyclic antidepressant use vs none: 1.12 (0.91-1.37)
Amitriptyline: 1.10 (0.85-1.42)
Imipramine: 0.88 (0.51-1.51)
Doxepin: 1.21 (0.70-2.10)
Any MAO-I use vs none: 0.87 (0.35-2.14)
Gonzalez-Perez and Garcia Rodriguez (38) UK1995-2001Registry-based studyCases: 3,708 cases of invasive breast cancer identified from General Practice ResearchGeneral practice database/electronic medical recordPast SSRI use vs none: 0.81 (0.67-1.00)Age, calendar year, BMI, alcohol consumption, prior benign breast disease, depression, NSAID use, and HRT use
DatabaseSSRI duration >3 y vs none: 0.56 (0.27-1.18)
Controls: 20,000 controls frequency matched on age, calendar yearSSRI high dose vs none: 0.95 (0.46-1.96)
Past tricyclic antidepressant use vs none: 0.92 (0.80-1.05)
Tricyclic antidepressant duration >3 y vs none: 0.83 (0.62-1.09)
Tricyclic antidepressant high dose vs none: 1.11 (0.71-1.71)
Haque et al. (39) USA1995-2000Registry-based study635 cases identified via Kaiser Permanente Southern California health plan cancer registry filesLarge health plan database/electronic medical recordEver used paroxetine vs never: 1.12 (0.96-1.31)AgeEntire cohort use antidepressants, so controls were users of other medications
Cohort: 109,004 women health plan members with a history of antidepressant useUsed paroxetine ≥2 y vs never: 0.90 (0.66-1.23)
Coogan et al. (37) USA1988-2002Hospital-based case-control studyCases: 2,138 cases of primary, invasive breast cancer identified via discharge summaries and pathology reportsIn-person interviewsRegular SSRI use vs none: 1.1 (0.8-1.7)Age, study center, year of interview, alcohol consumption, religion, family history of breast cancer, and race
Controls: 2,858 patients without cancer diagnoses frequency matched to cases on age, study center, and interview yearParoxetine vs none: 0.8 (0.3-2.3)
Regular SSRI duration ≥4 y vs none: 0.7 (0.4-1.5)
Fluoxetine duration ≥4 y vs none: 0.9 (0.4-2.2)
Sertraline duration ≥4 y vs none: 1.0 (0.3-4.1)
Fulton-Kehoe et al. (23) USA1990-2001Population-based case-control studyCases: 2,904 cases of primary invasive or in situ breast cancer in women enrolled in a large HMO, identified via Surveillance, Epidemiology and End ResultsHealth plan prescription database, self-administered questionnaireEver use antidepressants vs never: 1.04 (0.94-1.16)Age, length of enrollment, calendar year, family history of breast cancer, parity/age at first birth, duration of HRT use, BMI, history of screening mammogram in 2 y before reference date
Controls: 14,396 disease-free controls matched 5:1 to cases on age, calendar year, and length of HMO membershipAny antidepressant, 51+ Rx: 1.12 (0.89-1.41)
Ever tricyclic antidepressant vs none: 1.06 (0.94-1.19)
Ever amitriptyline: 1.21 (1.03-1.41)
Ever doxepine: 0.95 (0.79-1.13)
Ever imipramine: 1.04 (0.84-1.29)
Ever SSRI vs none: 0.98 (0.80-1.18)
Any SSRI + Rx: 1.04 (0.73-1.48)
Ever fluoxetine: 1.00 (0.80-1.25)
Ever paroxetine: 1.00 (0.70-1.41)
Ever sertraline: 1.16 (0.81-1.66)
Lokugamage et al. (24) UK1946-2005CohortCohort of 2,253 women followed from birthIn-person interviewsUse of an antidepressant at age 31 or 36 vs never use: 0.75 (0.27-2.05)None
Cases: 83 women with incident breast cancer
Chien et al. (25) USA1997-1999Population-based case-control studyCases: 975 women age 65-79 y with primary invasive cancerIn-person interviewEver antidepressant use vs never: 1.2 (0.9-1.6)Age, year, county of residenceAdjustment for following variables did not appreciably effect risk estimates: race, income, marital status, education, time since last medical checkup, age at menarche, parity, age at first birth, type of menopause, age at menopause, duration of contraceptive use, menopausal hormone use, family history of breast cancer, tobacco smoking, alcohol consumption, BMI, and various medical conditions
Controls: 1,007 women matched on age, year, and county of residenceAntidepressant use among +FHx: 0.4 (0.2-0.9), antidepressant use among -FHx: 1.5 (1.1-2.0)
Antidepressant use among ER+: 1.2 (0.9-1.6), antidepressant use among ER-: 1.6 (1.0-2.8)
Antidepressant use among PgR+: 1.1 (0.8-1.5), antidepressant use among PgR-: 1.7 (1.1-2.5)
Ever tricyclic antidepressant use vs none: 1.2 (0.8-1.8), ever tricyclic antidepressant among +FHx: 0.5 (0.2-1.3), ever tricyclic antidepressant among -FHx: 1.5 (0.9-2.3)
Ever SSRI use vs none: 1.2 (0.8-1.8), ever SSRI among +FHx: 0.4 (0.2-1.0), ever SSRI among -FHx: 1.4 (0.9-2.2)