Antipsychotic therapy and breast cancer risk: a comprehensive systematic review and meta-analysis

While studies have shown a possible link between antipsychotic medication and the development of breast cancer, results remain inconclusive. The aim of the study was to assess the relationship between antipsychotic therapy and breast cancer risk, providing relevant determinative insights.

A systematic database search was conducted in PubMed, ScienceDirect, and Cochrane Library databases, along with a manual search of references, until October 13th, 2025, for literature on studies investigating the association between antipsychotic therapy and breast cancer in women. Primary analysis involved an overall hazard ratio meta-analysis, with secondary odds ratio analysis for complementary evidence. Further subgroup and meta-regression analyses were conducted. Subgroup and meta-regression analyses aimed to address heterogeneity and examine any potential association between the factors that varied, and the outcomes reported. The present meta-analysis was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.

Seventeen studies with 3,347,235 patients were included. Results support that exposure to antipsychotics leads to an overall 21% increased risk for breast cancer (HR = 1.21, 95% CI 1.03-1.42) compared to no exposure, which was more pronounced among retrospective studies. Furthermore, prolactin (PRL)-increasing antipsychotics pose an elevated risk (HR: 1.23, 95% CI 1.08-1.40) compared to PRL-sparing or none. Additionally, prolonged duration of therapy overall was associated with increased breast cancer risk (> 5 years: HR: 1.47, 95% CI 1.22-1.76), when compared to therapy for less than 1 year. Furthermore, first generation antipsychotics (FGAs) showed a significant association with duration (OR: 1.46, 95%CI 1.32-1.62), although second generation antipsychotics (SGAs) had no statistically significant results (OR: 1.09, 95% CI 0.94-1.25).

There is a statistically significant association between breast cancer risk in women and the use of antipsychotics. PRL-increasing medications seem to have a higher correlation with breast cancer risk compared to PRL-sparing drugs. Longer duration of exposure to FGAs results in a higher risk of breast cancer. While these findings are hypothesis-generating, they underline the need for definitive prospective studies accounting for confounding factors. Careful consideration of medical history is required when choosing antipsychotic therapy to optimize both effectiveness and safety.