The role of H1 antihistamines in contralateral breast cancer: a Danish nationwide cohort study



Preclinical studies have shown both pro- and antineoplastic effects of antihistamines. Here, we evaluated the effect of H1 antihistamines on contralateral breast cancer (CBC) risk, and whether cationic amphiphilic (CAD) antihistamines could increase the sensitivity to chemotherapy.


From the Danish Breast Cancer Group clinical database, we identified all women aged ≥20 years with a first-time diagnosis of breast cancer during 1996–2012. Information on drug use, CBC and potential confounding factors was retrieved from nationwide registries. Using Cox proportional hazard regression models, we calculated hazard ratios (HRs) and 95% confidence intervals (CIs) for CBC associated with H1-antihistamine use.


We identified 52,723 patients with breast cancer with a total of 310,583 person-years of follow-up. Among them, 1444 patients developed a new primary tumour in the contralateral breast. Post-diagnosis use of H1 antihistamines (≥2 prescriptions) was not strongly associated with CBC risk (HR 1.08, 95% CI: 0.90–1.31) compared with non-use (<2 prescriptions). Use of CAD antihistamines among patients receiving chemotherapy was not associated with a decrease in CBC risk.


Taken together, our findings do not suggest any association of H1-antihistamine use with CBC development.

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Author information

A.B., L.M., S.F., D.C.F., N.K., B.E. and M.J. participated in writing the study protocol. M.J. and B.E. provided data for the study. A.B., L.M., S.F., C.D. and D.C.F. wrote the data analyses plan. L.M., C.D. (statistical analyses) and T.L.L. (quantitative bias analysis) provided supervision. A.B. performed the statistical analyses and drafted and coordinated the revision of the paper. All authors contributed to the critical revision of the papert.

Correspondence to Lene Mellemkjær.

Ethics declarations

Ethics approval and consent to participate

The study was approved by the Danish Data Protection Agency (J. no. 2012-41-0284). In Denmark, approvals from Ethical Committees are not required for register-based studies that do not involve biological samples.

Data availability

The study was approved by the Danish Data Protection Board. Data were available from the Danish Breast Cancer Group (http://www.dbcg.dk/), Statistics Denmark (https://www.dst.dk/en/TilSalg/Forskningsservice) and the Research Service of Sundhedsdatastyrelsen (https://sundhedsdatastyrelsen.dk/da/forskerservice). R-code of analyses is available from the corresponding author upon request.

Competing interests

Maj-Britt Jensen has received grants from AstraZeneca, Celgene and Novartis, and Bent Ejlertsen from NanoString, Novartis and Roche, both outside the submitted work. Lene Mellemkjær has an immediate family member employed at Novo Nordisk and has an immediate family member who owns stocks in Novo Nordisk. All other authors declared no conflicts of interest.

Funding information

This work was supported by the Danish Research Council for Independent Research [grant number 11-108395].

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Bens, A., Dehlendorff, C., Friis, S. et al. The role of H1 antihistamines in contralateral breast cancer: a Danish nationwide cohort study. Br J Cancer 122, 1102–1108 (2020). https://doi.org/10.1038/s41416-020-0747-4

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