Risk of Breast Cancer in Association with the Use of Second-generation Antipsychotics.

Objective: Previous studies regarding the relationship between the risk of breast cancer (BC) and antipsychotics use have reported inconsistent findings. Insufficient sample size and/or observation period may have hindered revealing the risk of BC associated with antipsychotics use. We aimed to investigate whether the use of second-generation antipsychotics (SGA) is associated with increased risk of BC. Methods: We used the Health Insurance Review Agency database in South Korea between 2008 and 2018. The index date was determined as the date of the first antipsychotic prescription. We selected women prescribed SGAs for more than 30 days within a year from the index date and age-matched controls, yielding 498,970 cases and 997,940 controls. The Cox proportional hazards regression model was used for estimating the risk. Results: The incidence rates of BC were 109.74 and 101.51 per 100,000 person-years in the case and control groups, respectively. There was an increased risk of BC in the case group (hazard ratio [HR] = 1.08, 95% confidence interval [CI] 1.04-1.13). There was a higher risk of BC in subjects prescribed with ≥ 10,000 mg of olanzapine equivalent dose (HR = 1.29, 95% CI 1.14-1.46) than those with < 10,000 mg (HR = 1.05, 95% CI 1.00-1.11). The increased risk of BC in the case group became significant after six years of the observation period (≥ 6 years: HR = 1.24, 95% CI 1.14-1.35, 3 to < 6 years: HR = 1.06, 95% CI 0.97-1.15, < 3 years: HR = 1.02, 95% CI 0.95-1.09). Conclusion: This study indicated that the use of SGAs is associated with increased risk of BC in a long-term relationship with a dose-response pattern.