Antipsychotic drugs raising prolactin elevate risk of breast cancer in women

20th December 2021

Antipsychotic drugs especially those elevating prolactin levels appears to be associated with an increased risk of breast cancer in women

A study of antipsychotic drugs used by women has revealed an increased risk of breast cancer, which is worse in those drugs which elevate prolactin levels. This was the conclusion by researchers from the Department of Psychiatry, Washington, US.

Over expression of the prolactin (PRL) receptor is seen in more than 95% of human breast cancers and in fact, hyperprolactinaemia inducing antipsychotics cause precancerous cells to progress to cancer via JAK/STAT5 to suppress the apoptosis anticancer barrier. However, although data shows an increasing body of evidence supporting the involvement of PRL in breast carcinogenesis, results of human prospective studies are limited, equivocal, and correlative.

For the present analysis, the US team undertook a large epidemiological study, seeking to examine breast cancer risk by categorising antipsychotic drugs based on their ability to raise prolactin levels. Using lithium and anticonvulsants as a comparator, the researchers turned to a commercial health insurance database and identified women between the ages of 18 and 64 with an outpatient prescription for an antipsychotic, anticonvulsant or lithium between 2007 and 2016. They separated antipsychotics into three categories (1, 2 and 3) based on the propensity to raise prolactin, with drugs in category 1 being the highest. Examples included in the different categories were typical neuroleptics such as haloperidol, risperidone (category 1), olanzepine (category 2) and clozapine, quetiapine (category 3). The team identified invasive breast cancer from coding in the medical records and used multivariable Cox hazard models to evaluate the risk of breast cancer and adjusted for several factors including benign breast diseases, smoking, diabetes etc.

Findings

A total of 312,702 women with a median age of 41 years were identified as new users of antipsychotic drugs and 228, 035 women with a median age of 39 years, who were new users of anticonvulsants. From the whole sample, 914 women (0.2%) with a median age of 53 years, developed invasive breast cancer.

Women with use of any antipsychotic medication has a higher overall risk of breast cancer compared to those taking anticonvulsants or lithium (hazard ratio, HR = 1.40, 95% CI 1.19 – 1.64) although after adjustment, the hazard ratio reduced to 1.35 (95% CI 1.14 – 1.61).

In fully adjusted models, for the highest prolactin elevating category (1), the adjusted hazard ratio, aHR was 1.62 (95% CI 1.30 – 2.03), 1.54 (95% CI 1.19 – 1.99) for category 2 and non-significant for category 3. When analysing by age, younger women remained at an increased risk after adjustment (aHR = 1.91, 95% CI 1.21 – 3.01) compared to women aged 51 to 64 years (aHR = 1.43, 95% CI 1.01 – 2.03).

Discussing these findings, the authors noted how women using category 1 and 2 antipsychotic drugs had a significantly elevated risk of breast cancer compared to the comparator drugs. They suggested that younger women prescribed category 1 or 2 drugs should be considered for more frequent mammography screening.

Citation

Rahman T et al. Risk of Breast Cancer With Prolactin Elevating Antipsychotic Drugs. An Observational Study of US Women (Ages 18–64 Years) J Clin Psychopharmacol 2021