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Dopamine Antagonists and the Development of Breast Cancer
Philip S. Wang, MD,DrPH;
Alexander M. Walker, MD,DrPH;
Ming T. Tsuang, MD,PhD,DSc;
E. John Orav, PhD;
Robert J. Glynn, PhD,ScD;
Raisa Levin, MS;
Jerry Avorn, MD
Arch Gen Psychiatry. 2002;59:1147-1154.
Background Although animal studies have raised the possibility that prolactin-elevating dopamine antagonists used to treat psychotic disorders may initiate and promote breast cancers, epidemiologic studies in humans have been limited and inconsistent.
Methods A retrospective cohort study was conducted of 52 819 women exposed and 55 289 not exposed to dopamine antagonists between January 1, 1989, and June 30, 1995. All participants were 20 years or older, initially free of breast cancer, and enrolled in the Medicaid or the Pharmaceutical Assistance to the Aged and Disabled programs of New Jersey. Incident breast cancer cases were identified through the New Jersey Cancer Registry and definitive breast cancer surgeries. Adjusted hazard ratios of breast cancer were calculated from multivariable proportional hazards models.
Results Use of antipsychotic dopamine antagonists was associated with a 16% increase in the risk of breast cancer (adjusted hazard ratio, 1.16; 95% confidence interval, 1.07-1.26), with a dose-response relationship between larger cumulative dosages and greater risk. The increased risk was also seen in women who used prolactin-elevating antiemetic dopamine antagonists despite having different breast cancer risk profiles than antipsychotic dopamine antagonist users. Dopamine antagonist use was not associated with risk of colon cancer, a control condition not related to elevated prolactin levels. The increased risk of breast cancer among dopamine antagonist users was not explained by increased surveillance or protopathic bias.
Conclusions Antipsychotic dopamine antagonist use may confer a small but significant risk of breast cancer. In light of the small hazards and the possibility of residual confounding, these findings should lead to follow-up investigations but not to changes in treatment strategies.
From the Division of Pharmacoepidemiology and Pharmacoeconomics (Drs Wang, Glynn, and Avorn and Ms Levin) and the Clinical Epidemiology Section (Dr Orav), Brigham and Women's Hospital, Harvard Medical School; the Department of Epidemiology, Harvard School of Public Health (Drs Wang, Walker, and Tsuang); and the Harvard Institute of Psychiatric Epidemiology and Genetics and the Massachusetts Mental Health Center, Harvard Medical School (Dr Tsuang), Boston.
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