Breast cancer and spironolactone: an observational postmarketing study
Recent studies have discussed the risk of breast cancer with antihypertensive drugs. For spironolactone, data are conflicting. The present paper investigates this potential signal in VigiBase®, the World Health Organization Global Individual Case Safety Report (ICSR) database.
In VigiBase®, we performed a case/non-case study using data registered from 1981 (spironolactone’s marketing authorization) to December 31, 2017. Among women ≥ 50 years, we measured the risk of reporting “Breast malignant tumors” compared with all other adverse drug reactions (as a crude and adjusted (a) reporting odds ratio (ROR 95% CI)) for spironolactone compared with first, all other drugs and second, pseudo aldosterone antagonists (amiloride, triamterene). ROR were adjusted for age, year of report, continent of report, number of drug prescribed, and completeness score. Sensitivity analyses were performed after exclusion of drug competitors (i.e., drugs like estroprogestative therapy and progestogens that could mask a putative signal) and reports from health professionals.
During the study period, 125 ICSRs reported spironolactone exposure and breast malignant cancer in women ≥ 50 years. We failed to find a positive association between spironolactone exposure and breast cancer in comparison with exposure to other drugs (aROR = 0.63 95% CI [0.52–0.75]) or pseudo aldosterone antagonists (amiloride, triamterene) (0.56 [0.44–0.72]). Similar trends were found after exclusion of drug competitors and/or reports from health professionals.
This study did not find evidence for breast cancer associated with spironolactone.
KeywordsSpironolactone Breast cancer Antialdosterone
The authors would like to thank the Uppsala Monitoring Centre (UMC) which provided and gave permission to use the data analyzed in the present study. The authors are indebted to the National Pharmacovigilance Centers that contributed data.
JA and BB suggested the topic of the study. PS, FM, JLM, and VR designed the study. PS and VR performed the statistical analysis. LC collected the reports. PS, FM, and JLM analyzed the data. PS, FM, and JLM wrote the paper. All authors reviewed the successive versions of the manuscript and approved the final version.
Compliance with ethical standards
JA is a co-founder, shareholder, and consultant of VAIOMER (www.vaiomer.com), a biotech company which specializes in tissue and blood microbiota analyses. He is at the editorial board of “La revue des microbiotes,” a journal sponsored by PiLeJe Laboratories. He received consultancy fees or support to attend meetings or grants for research from almost all companies marketing antihypertensive drugs. BB received consultancy fees or supports to attend meeting from Astra-Zeneca, Bouchara-Recordati, Lilly, Novartis, Novo-Nordisk, Sanofi, Servier, Takeda, and MSD, but she had no competing interest concerning this article. The other authors have no competing interests.
The opinions and conclusions in this study are not necessarily those of the various centers or of the WHO or ANSM (Agence Nationale de Sécurité du Médicament et des produits de santé, France).
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