¹UMCG, Center for Clinical Neuroscience and Cognition, Groningen, Netherlands, ²Vrije Universiteit Amsterdam, Medical Sciences, Amsterdam, Netherlands, ³University College Dublin, Department of Psychiatry, Dublin, Ireland, ⁴Technical University of Munich, Section for Evidence-based Medicine in Psychiatry and Psychotherapy, Munich, Germany

Background: While antipsychotics may have different effects in men and women, no sex-specific guideline recommendations for first-choice medications currently exist. Antipsychotics can be classified according to their effects on prolactin. Most first generation antipsychotics are prolactin-raising, compared to other medications like aripiprazole, which are prolactin-sparing. Higher blood levels of prolactin have previously been associated with higher breast cancer risk. More evidence is needed to assess breast cancer risk due to prolactin properties in antipsychotics in women.

Aims & Objectives: This meta analysis aims to assess breast cancer risk in women using antipsychotics, comparing different prolactin levels.

Method: A search strategy of multiple databases evaluating breast cancer risk due to antipsychotic use based on prolactin levels has been conducted. A total of 14 studies (2002-2025) from 8 different countries were included (N = 2,966,377), of which 7 were cohort studies and 7 were case-control. Pooled estimates of hazard ratio (HR) or odds ratio (OR) were extracted and analysed using random-effects models.

Results: Across the seven cohort studies, exposure to prolactin-raising antipsychotics was associated with a 57% increased risk of breast cancer in women (log effect estimate = 0.45, SE = 0.11; z = 4.00, p < 0.0001). When looking at case-controlled studies, exposure was associated with 21% increased risk of breast cancer (log effect estimate = 0.19, SE = 0.09; z = 2.12, p = 0.0338).

Discussion & Conclusions: Use of prolactin-raising antipsychotics was shown to be associated with an increased risk of developing breast cancer. These findings support the idea of needing sex-specific guidelines in order to limit severe side effects due to medication use, for which currently no recommendations specifically for women exist.