Advertisement

Breast cancer and spironolactone: an observational postmarketing study

  • Pierre Sabatier
  • Jacques Amar
  • François Montastruc
  • Vanessa Rousseau
  • Leila Chebane
  • Béatrice Bouhanick
  • Jean-Louis MontastrucEmail author
Pharmacoepidemiology and Prescription

Abstract

Introduction

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.

Methods

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.

Results

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.

Conclusion

This study did not find evidence for breast cancer associated with spironolactone.

Keywords

Spironolactone Breast cancer Antialdosterone 

Notes

Acknowledgments

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.

Authors’ role

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

Competing interests

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.

Disclaimer

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).

References

  1. 1.
    Largent JA, McEligot AJ, Ziogas A, Reid C, Hess J, Leighton N, Peel D, Anton-Culver H (2006) Hypertension, diuretics and breast cancer risk. J Hum Hypertens 20:727–732CrossRefGoogle Scholar
  2. 2.
    Gómez-Acebo I, Dierssen-Sotos T, Palazuelos C, Pérez-Gómez B, Lope V, Tusquets I, Alonso MH, Moreno V, Amiano P, Molina de la Torre AJ, Barricarte A, Tardon A, Camacho A, Peiro-Perez R, Marcos-Gragera R, Muñoz M, Michelena-Echeveste MJ, Ortega Valin L, Guevara M, Castaño-Vinyals G, Aragonés N, Kogevinas M, Pollán M, Llorca J, Gómez-Acebo I, Dierssen-Sotos T, Palazuelos C, Pérez-Gómez B, Lope V, Tusquets I, Alonso MH, Moreno V, Amiano P, de la Torre AJ M, Barricarte A, Tardon A, Camacho A, Peiro-Perez R, Marcos-Gragera R, Muñoz M, Michelena-Echeveste MJ, Ortega Valin L, Guevara M, Castaño-Vinyals G, Aragonés N, Kogevinas M, Pollán M, Llorca J (2016) The use of antihypertensive medication and the risk of breast cancer in a case-control study in a Spanish population: the MCC-Spain study. PLoS One 11:e0159672CrossRefGoogle Scholar
  3. 3.
    Li CI, Malone KE, Weiss NS, Boudreau DM, Cushing-Haugen KL, Daling JR (2003) Relation between use of antihypertensive medications and risk of breast carcinoma among women ages 65-79 years. Cancer 98:1504–1513CrossRefGoogle Scholar
  4. 4.
    Zhao Y, Wang Q, Zhao X, Meng H, Yu J (2018) Effect of antihypertensive drugs on breast cancer risk in female hypertensive patients: evidence from observational studies. Clin Exp Hypertens 40:22–27CrossRefGoogle Scholar
  5. 5.
    Jackson EK (2018) Drugs affecting renal excretory function. In: Brunton LL, Hilal-Dandan R, Knollmann BJ (eds) Goodman and Gilman’s the pharmacological basis of therapeutics, 13th edn. New York, Mc Graw Hill, pp 445–470Google Scholar
  6. 6.
    Miyatake A, Noma K, Nakao K, Morimoto Y, Yamamura Y (1978) Increased serum oestrone and oestradiol following spironolactone administration in hypertensive men. Clin Endocrinol 9:523–533CrossRefGoogle Scholar
  7. 7.
    Biggar RJ, Andersen EW, Wohlfahrt J, Melbye M (2013) Spironolactone use and the risk of breast and gynecologic cancers. Cancer Epidemiol 37:870–875CrossRefGoogle Scholar
  8. 8.
    Mackenzie IS, Macdonald TM, Thompson A, Morant S, Wei L (2012) Spironolactone and risk of incident breast cancer in women older than 55 years: retrospective, matched cohort study. BMJ 345:e4447CrossRefGoogle Scholar
  9. 9.
    Mackenzie IS, Morant SV, Wei L, Thompson AM, MacDonald TM (2017) Spironolactone use and risk of incident cancers: a retrospective, matched cohort study. Br J Clin Pharmacol 83:653–663CrossRefGoogle Scholar
  10. 10.
    Bate A, Lindquist M, Edwards IR (2008) The application of knowledge discovery in databases to post-marketing drug safety: example of the WHO database. Fundam Clin Pharmacol 22:127–140CrossRefGoogle Scholar
  11. 11.
    Bergvall T, Norén GN, Lindquist M (2014) VigiGrade: a tool to identify well-documented individual case reports and highlight systematic data quality issues. Drug Saf 37:65–77CrossRefGoogle Scholar
  12. 12.
    Edwards IR, Aronson JK (2000) Adverse drug reactions: definitions, diagnosis and management. Lancet 356:1255–1259CrossRefGoogle Scholar
  13. 13.
    Montastruc JL, Sommet A, Bagheri H, Lapeyre-Mestre M (2011) Benefits and strengths of the disproportionality analysis for identification of adverse drug reactions in a pharmacovigilance database. Br J Clin Pharmacol 72:905–908CrossRefGoogle Scholar
  14. 14.
    Faillie JL (2019) Case-non case studies: principles, methods, bias and interpretation. Therapie 74:225–232CrossRefGoogle Scholar
  15. 15.
    Key TJ, Verkasalo PK, Banks E (2001) Epidemiology of breast cancer. Lancet Oncol 2:133–140CrossRefGoogle Scholar
  16. 16.
    Fentiman IS (2016) Male breast cancer is not congruent with the female disease. Crit Rev Oncol Hematol 101:119–124CrossRefGoogle Scholar
  17. 17.
    Anders CK, Johnson R, Litton J, Phillips M, Bleyer A (2009) Breast cancer before age 40 years. Semin Oncol 36:237–249CrossRefGoogle Scholar
  18. 18.
    Assi HA, Khoury KE, Dbouk H, Khalil LE, Mouhieddine TH, El Saghir NS (2013) Epidemiology and prognosis of breast cancer in young women. J Thorac Dis 5(Suppl 1):S2–S8Google Scholar
  19. 19.
    (1975) Editorial: reserpine and breast cancer. Can Med Assoc J 112:129Google Scholar
  20. 20.
    Grossman E, Messerli FH, Goldbourt U (2001) Antihypertensive therapy and the risk of malignancies. Eur Heart J 22:1343–1352CrossRefGoogle Scholar
  21. 21.
    Pariente A, Avillach P, Salvo F, Thiessard F, Miremont-Salamé G, Fourrier-Reglat A, Haramburu F, Bégaud B, Moore N, Association Française des Centres Régionaux de Pharmacovigilance (CRPV) (2012) Effect of competition bias in safety signal generation: analysis of a research database of spontaneous reports in France. Drug Saf 35:855–864CrossRefGoogle Scholar
  22. 22.
    Bezin J, Bosco-Levy P, Pariente A (2017) False-positive results in pharmacoepidemiology and pharmacovigilance. Therapie 72:415–420CrossRefGoogle Scholar
  23. 23.
    Vial T (2016) French pharmacovigilance: missions, organization and perspectives. Therapie 71:143–150CrossRefGoogle Scholar
  24. 24.
    Loube SD, Quirk RA (1975) Breast cancer associated with administration of spironolactone. Lancet 1(7922):1428–1429CrossRefGoogle Scholar
  25. 25.
    Shaw JC (1991) Spironolactone in dermatologic therapy. J Am Acad Dermatol 24:236–243CrossRefGoogle Scholar
  26. 26.
    Cunliffe WJ (1992) Spironolactone in dermatology. J Am Acad Dermatol 26:137–138CrossRefGoogle Scholar
  27. 27.
    Montastruc JL, Benevent J, Montastruc F, Bagheri H, Despas F, Lapeyre-Mestre M, Sommet A (2019) What is pharmacoepidemiology? Definition, methods, interest and clinical applications. Therapie 74:169–174CrossRefGoogle Scholar
  28. 28.
    Abrahami D, Douros A, Yin H, Yu OH, Faillie JL, Montastruc F, Platt RW, Bouganim N, Azoulay L (2018) Incretin based drugs and risk of cholangiocarcinoma among patients with type 2 diabetes: population based cohort study. BMJ. 363:k4880.  https://doi.org/10.1136/bmj.k4880 CrossRefGoogle Scholar
  29. 29.
    Hazell L, Shakir SA (2006) Under-reporting of adverse drug reactions: a systematic review. Drug Saf 29:385–396CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Service de Pharmacologie Médicale et Clinique, Centre de PharmacoVigilance, de Pharmaco-épidémiologie et d’Informations sur le Médicament, CIC INSERM 1436, UMR INSERM 1027Faculté de Médecine - Centre Hospitalier UniversitaireToulouseFrance
  2. 2.Service Hypertension Artérielle et Thérapeutique, Centre Hospitalier Universitaire, UMR INSERM 1027ToulouseFrance

Personalised recommendations