Antipsychotic Drugs and the Risk of Breast Cancer

Objective Antipsychotic drugs are well established to alter circulating prolactin levels by blocking dopamine D-2 receptors in the pituitary. Prolactin activates many genes important in the development of breast cancer. The aim of this study was to evaluate the risk of breast cancer in women exposed to antipsychotic drugs, stratified by prolactin elevating potential (high, mid, and low), compared to women taking anticonvulsants and/or lithium. Methods The IBM MarketScan Commercial and Medicaid Databases were used to establish a large, observational cohort of women taking antipsychotics drugs compared to control drugs. Invasive breast cancer was identified using diagnostic codes. Bivariable and multivariable Cox proportional hazards models were used to evaluate the risk of breast cancer by antipsychotic drug exposure, both as pooled antipsychotics and by prolactin specific categories. Results A total of 2,708 (0.2%) cases of invasive breast cancer were identified among 1,562,839 women. Exposure to antipsychotics with high prolactin elevating potential was associated with a 23% increased risk of breast cancer (aHR 1.23; 95% CI, 1.11-1.35), whereas mid and low prolactin categories of antipsychotics were not significant. Conclusion In the largest study of antipsychotics taken by women, a modest risk between antipsychotic drug use and the risk for breast cancer was observed, with a differential higher association with high prolactin elevating drugs. Residual confounding factors included incomplete information on parity, race and socioeconomic status, and differential outpatient visits. Clinicians should consider monitoring serum prolactin levels and adopting vigilant mammography screening practices, especially in older women taking category one antipsychotics.