Antipsychotic Dopamine Antagonists May Increase Breast Cancer Risk

Laurie Barclay, MD

December 27, 2002

Dec. 27, 2002 — Women using antipsychotic dopamine antagonists had a 16% increased risk of developing breast cancer, according to results of a retrospective study published in the December issue of the Archives of General Psychiatry. Although these findings are preliminary and should not alter medication use, they should prompt increased surveillance in schizophrenics, who usually have lower rates of breast cancer screening.

"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," write Philip S. Wang, MD, DrPH, from Brigham and Women's Hospital in Boston, Massachusetts, and colleagues.

This retrospective cohort study analyzed data from 52,819 women exposed and 55,289 not exposed to dopamine antagonists between January 1, 1989, and June 30, 1995. All subjects were at least 20 years of age, initially free of breast cancer, and enrolled in the Medicaid or the Pharmaceutical Assistance to the Aged and Disabled programs of New Jersey.

Use of antipsychotic dopamine antagonists was linked to increased risk of breast cancer (adjusted hazard ratio, 1.16; 95% confidence interval, 1.07-1.26) but not of colon cancer. Larger cumulative dosages were associated with greater risk, suggesting a dose-response relationship.

Women who used prolactin-elevating antiemetic dopamine antagonists were also at increased risk, even though they had different breast cancer risk profiles than antipsychotic dopamine antagonist users. Increased surveillance or protopathic bias among dopamine antagonist users did not explain the increased risk of breast cancer.

The magnitude of the risk observed was statistically significant but small in absolute terms. The authors note that even if their preliminary results are verified, there is less than a 14% chance that a dopamine antagonist user who develops breast cancer did so on the basis of her antipsychotic drug use.

"Antipsychotic dopamine antagonist use may confer a small but significant risk of breast cancer," the authors write. "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. . … Women who use antipsychotic medications are less likely to receive breast cancer surveillance through mammography and outpatient medical visits. Rather than receiving such diminished levels of care, our results suggest that patients with psychotic disorders may require enhanced monitoring for cancer and care of their general medical disorders."

Arch Gen Psychiatry. 2002;59:1147-1154

Reviewed by Gary D. Vogin, MD

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