Antipsychotic use and risk of breast cancer in women with schizophrenia: a nationwide nested case-control study in Finland

Abstract

Background: Breast cancer is more common in female patients with schizophrenia than in the general population. It is not known whether treatment with prolactin-increasing antipsychotics contributes to increased odds of breast cancer.

Methods: We used Finnish nationwide registers of hospital treatment, prescription drug purchases, and cancer diagnoses to do a nested case-control study. Of women with schizophrenia, those with breast cancer (cases) were matched by age and duration of illness with five women without cancer (controls). Cases and controls were aged 18-85 years and exclusion criteria were any previous cancer diagnoses, receipt of organ transplant, mastectomy, or diagnosis of HIV. The main analysis was the association between cumulative exposure to prolactin-increasing drugs and breast cancer. The analyses were done with conditional logistic regression, by adjusting for comorbid conditions and concomitant medications. Ethnicity data were not available.

Findings: Of 30 785 women diagnosed with schizophrenia between 1972 and 2014, 1069 were diagnosed with breast cancer between Jan 1, 2000, and Dec 31, 2017. Compared with 5339 matched controls, 1-4 years cumulative exposure (adjusted odds ratio [OR] 0·95, 95% CI 0·73-1·25) or 5 or more years exposure (adjusted OR 1·19, 0·90-1·58) to prolactin-sparing antipsychotics (including clozapine, quetiapine, or aripiprazole) was not associated with an increased risk of breast cancer in comparison with minimal exposure (<1 year). When compared with less than 1 year of exposure to prolactin-increasing antipsychotics (all other antipsychotics), 1-4 years of exposure was not associated with an increased risk, but exposure for 5 or more years was associated with an increased risk (adjusted OR 1·56 [1·27-1·92], p<0·001). The risk for developing lobular adenocarcinoma associated with long-term use of prolactin-increasing antipsychotics (adjusted OR 2·36 [95% CI 1·46-3·82]) was higher than that of developing ductal adenocarcinoma (adjusted OR 1·42 [95% CI 1·12-1·80]).

Interpretation: Long-term exposure to prolactin-increasing, but not to prolactin-sparing, antipsychotics is significantly associated with increased odds of breast cancer. Monitoring prolactinemia and addressing hyperprolactinemia is paramount in women with schizophrenia being treated with prolactin-increasing antipsychotics.

Funding: Finnish Ministry of Social Affairs and Health.