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Front Oncol. 2012 Dec 05;2:177. doi: 10.3389/fonc.2012.00177. eCollection 2012.

Selective Serotonin Reuptake Inhibitor (SSRI) Antidepressants, Prolactin and Breast Cancer.

Frontiers in oncology

Janet E Ashbury, Linda E Lévesque, Patricia A Beck, Kristan J Aronson

Affiliations

  1. Department of Community Health and Epidemiology, Carruthers Hall, Queen's University Kingston, ON, Canada.

PMID: 23227451 PMCID: PMC3514533 DOI: 10.3389/fonc.2012.00177

Abstract

Selective serotonin reuptake inhibitors (SSRIs) are a widely prescribed class of antidepressants. Laboratory and epidemiologic evidence suggests that a prolactin-mediated mechanism secondary to increased serotonin levels at neuronal synapses could lead to a potentially carcinogenic effect of SSRIs. In this population-based case-control study, we evaluated the association between SSRI use and breast cancer risk as a function of their relative degree of inhibition of serotonin reuptake as a proxy for their impact on prolactin levels. Cases were 2,129 women with primary invasive breast cancer diagnosed from 2003 to 2007, and controls were 21,297 women randomly selected from the population registry. Detailed information for each SSRI prescription dispensed was compiled using the Saskatchewan prescription database. Logistic regression was used to evaluate the impact of use of high and lower inhibitors of serotonin reuptake and duration of use, as well as to assess the effect of individual high inhibitors on the risk of breast cancer. Exclusive users of high or lower inhibitors of serotonin reuptake were not at increased risk for breast cancer compared with non-users of SSRIs (OR = 1.01, CI = 0.88-1.17 and OR = 0.91, CI = 0.67-1.25 respectively), regardless of their duration of use or menopausal status. While we cannot rule out the possibility of a clinically important risk increase (OR = 1.83, CI = 0.99-3.40) for long-term users of sertraline (≥24 prescriptions), given the small number of exposed cases (n = 12), the borderline statistical significance, and the wide confidence interval, these results need to be interpreted cautiously. In this large population-based case-control study, we found no conclusive evidence of breast cancer risk associated with the use of SSRIs even after assessing the degree of serotonin reuptake inhibition and duration of use. Our results do not support the serotonin-mediated pathway for the prolactin-breast cancer hypothesis.

Keywords: SSRIs; antidepressants; breast cancer; case-control studies; prolactin; selective serotonin reuptake inhibitors

References

  1. Clin Pharmacol Ther. 1989 Oct;46(4):371-86 - PubMed
  2. Am J Epidemiol. 2005 Nov 1;162(9):835-8 - PubMed
  3. J Clin Psychopharmacol. 2005 Jun;25(3):285-7 - PubMed
  4. J Clin Oncol. 2007 Apr 20;25(12):1482-8 - PubMed
  5. Cancer Res. 1977 Apr;37(4):951-63 - PubMed
  6. Int J Cancer. 2000 Aug 15;87(4):591-4 - PubMed
  7. J Mammary Gland Biol Neoplasia. 2008 Mar;13(1):41-53 - PubMed
  8. Cancer Res. 1992 Jul 1;52(13):3796-800 - PubMed
  9. Cancer Res. 2006 Feb 15;66(4):2476-82 - PubMed
  10. Br J Cancer. 2006 Apr 10;94(7):1071-8 - PubMed
  11. Int J Cancer. 2002 Apr 1;98(4):604-8 - PubMed
  12. Endocr Rev. 2003 Feb;24(1):1-27 - PubMed
  13. PLoS One. 2011 Apr 06;6(4):e18210 - PubMed
  14. Hum Psychopharmacol. 2010 Jun-Jul;25(4):281-97 - PubMed
  15. Eur J Pharmacol. 1997 Dec 11;340(2-3):249-58 - PubMed
  16. J Natl Cancer Inst. 1980 Sep;65(3):559-69 - PubMed
  17. Am Fam Physician. 2003 Aug 1;68(3):498-504 - PubMed
  18. Cancer Lett. 2005 Apr 18;221(1):61-5 - PubMed
  19. Breast Cancer Res Treat. 2008 Jun;109(3):527-31 - PubMed
  20. J Intern Med. 2007 Mar;261(3):205-13 - PubMed
  21. Mayo Clin Proc. 2005 Aug;80(8):1050-7 - PubMed
  22. BMJ. 2003 Jan 25;326(7382):219 - PubMed
  23. J Appl Toxicol. 2005 May-Jun;25(3):179-83 - PubMed
  24. Epidemiology. 2003 May;14(3):307-14 - PubMed
  25. Ment Health Serv Res. 2002 Jun;4(2):109-18 - PubMed
  26. Psychother Psychosom. 2003 Jul-Aug;72(4):185-94 - PubMed
  27. Gen Hosp Psychiatry. 2005 Jul-Aug;27(4):229-36 - PubMed
  28. Am J Public Health. 1989 Mar;79(3):340-9 - PubMed
  29. Neuropsychopharmacology. 2004 May;29(5):833-46 - PubMed
  30. Endocr Relat Cancer. 1999 Sep;6(3):389-404 - PubMed
  31. Breast Cancer Res Treat. 2006 Jan;95(2):131-40 - PubMed
  32. Pharmacoepidemiol Drug Saf. 2009 Apr;18(4):284-90 - PubMed
  33. BMC Med. 2010 Dec 22;8:90 - PubMed
  34. Pharmacoepidemiol Drug Saf. 2007 May;16(5):560-70 - PubMed
  35. Drug Saf. 2011 Dec 1;34(12):1161-6 - PubMed
  36. J Neuroendocrinol. 2010 Jul;22(7):771-7 - PubMed
  37. CMAJ. 2005 Jan 4;172(1):57-9 - PubMed
  38. Soc Sci Med. 2003 Mar;56(6):1335-44 - PubMed
  39. Ann Epidemiol. 2007 Jan;17(1):27-35 - PubMed
  40. Eur J Clin Pharmacol. 1997;52(3):205-9 - PubMed
  41. Epidemiology. 2005 Jan;16(1):101-5 - PubMed
  42. CNS Drugs. 2010 Jul;24(7):563-74 - PubMed
  43. Maturitas. 2010 Sep;67(1):60-6 - PubMed
  44. Arch Intern Med. 2004 Nov 22;164(21):2367-70 - PubMed
  45. Arch Gen Psychiatry. 1998 Apr;55(4):310-6 - PubMed
  46. J Natl Cancer Inst. 1987 May;78(5):993-8 - PubMed
  47. BMJ. 2001 Sep 22;323(7314):655-8 - PubMed
  48. Int J Epidemiol. 1992 Apr;21(2):222-8 - PubMed

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