Use of antipsychotics and risk of breast cancer: A Danish nationwide case-control study

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AIMS: Some antipsychotics increases prolactin levels, which might increase the risk of breast cancer. Existing evidence is conflicting and based on sparse data, especially for the increasingly used second-generation antipsychotics. We conducted a nationwide case-control study of the association between antipsychotic use and incident breast cancer.

METHODS: From the Danish Cancer Registry, we identified women with a first-time diagnosis of breast cancer 2000-2015 (n=60,360). For each case, we age-matched 10 female population controls. Using conditional logistic regression, we calculated odds ratios (ORs) for breast cancer associated with use of antipsychotics. We stratified antipsychotics by first and- second generation status and by ability to induce elevation of prolactin.

RESULTS: 4,951 cases (8.1%) and 47,643 controls (7.1%) had ever used antipsychotics. Long-term use (≥10,000 mg olanzapine equivalents) was associated with breast cancer, with an adjusted OR of 1.18 (95%CI, 1.06, 1.32). A weak dose-response pattern was seen, with ORs increasing to 1.27 (95% CI 1.01, 1.59) for ≥50,000mg olanzapine equivalents. Associations were similar for first- and second-generation antipsychotics (ORs 1.17 vs 1.11), but also for non-prolactin inducing antipsychotics (OR 1.17). Stratifying by estrogen receptor status, positive associations were seen for estrogen receptor positive cancers (long-term use: OR 1.29; 95% CI 1.13, 1.47) while no associations were observed for estrogen receptor negative cancers.

CONCLUSIONS: Overall, our results do not suggest a clinically important association between antipsychotic use and risk of breast cancer. The importance of drug-induced prolactin elevation is unclear but may lead slightly increased risk of estrogen receptor positive breast cancer.

JournalBritish Journal of Clinical Pharmacology
StateE-pub ahead of print - 2018