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Br J Clin Pharmacol. 2018 Sep;84(9):2152-2161. doi: 10.1111/bcp.13661. Epub 2018 Jul 8.

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

Author information

1
Clinical Pharmacology and Pharmacy, Department of Public Health, University of Southern Denmark, Odense, Denmark.
2
Department of Clinical Epidemiology, Aarhus University, Aarhus, Denmark.
3
Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia, USA.
4
Departments of Surgery and Biochemistry, Larner College of Medicine, University of Vermont, Burlington, Vermont, USA.
5
Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, Odense, Denmark.
6
Department of Clinical Research, University of Southern Denmark, Odense, Denmark.

Abstract

AIMS:

Some antipsychotics increase 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:

In total, 4951 cases (8.1%) and 47 643 controls (7.9%) 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% confidence interval (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 ≥50 000 mg olanzapine equivalents. Associations were similar for first- and second-generation antipsychotics (ORs 1.17 vs. 1.11), but also for nonprolactin inducing-antipsychotics (OR 1.17). Stratifying by oestrogen receptor status, positive associations were seen for oestrogen receptor-positive cancers (long-term use: OR 1.29; 95% CI 1.13, 1.47) while no associations were observed for oestrogen 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 to a slightly increased risk of oestrogen receptor-positive breast cancer.

KEYWORDS:

antipsychotics; breast cancer; pharmacoepidemiology

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