Skip to main content

Advertisement

Log in

Breast cancer recurrence risk in relation to antidepressant use after diagnosis

  • Epidemiology
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

Background While laboratory data suggest that antidepressants may promote mammary tumor growth, there has been little research investigating whether antidepressant use after breast cancer diagnosis is associated with the risk of breast cancer recurrence. Methods We conducted a retrospective cohort study within Group Health, an integrated healthcare delivery system in Washington state. Women diagnosed with a first primary invasive, stage I, IIA, or IIB, unilateral breast carcinoma between 1990–1994 (aged ≥65 years) and 1996–1999 (aged ≥18 years) were eligible for the study (N = 1306). Recurrence within 5-year of diagnosis was ascertained by medical chart review. We used the pharmacy database to identify antidepressant dispensings from Group Health pharmacies. We used multiple Cox regression to estimate the hazard ratio for recurrence and breast cancer mortality, comparing users and non-users of antidepressant medications. Results for recurrence were examined separately in users and non-users of tamoxifen. Results We did not observe an association between antidepressant use after breast cancer diagnosis and the risk of recurrence either in general (hazard ratio for any antidepressant use: 0.8; 95% confidence interval: 0.5–1.4) or for specific types of antidepressant medication. Risk of death from breast cancer did not differ between non-users and users of antidepressants. Conclusions The results of this study suggest that women who use antidepressants after breast cancer diagnosis do not have an increased risk of recurrence or mortality.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. McDaniel JS, Musselman DL, Porter MR, Reed DA, Nemeroff CB (1995) Depression in patients with cancer. Diagnosis, biology, and treatment. Arch Gen Psychiatry 52:89–99

    PubMed  CAS  Google Scholar 

  2. van’t Spijker A, Trijsburg RW, Duivenvoorden HJ (1997) Psychological sequelae of cancer diagnosis: a meta-analytical review of 58 studies after 1980. Psychosom Med 59:280–293

    PubMed  CAS  Google Scholar 

  3. Meeske K, Smith AW, Alfano CM, McGregor BA, McTiernan A, Baumgartner KB et al (2007) Fatigue in breast cancer survivors two to five years post diagnosis: a HEAL Study report. Qual Life Res 16:947–960

    Article  PubMed  Google Scholar 

  4. Ashbury FD, Madlensky L, Raich P, Thompson M, Whitney G, Hotz K et al (2003) Antidepressant prescribing in community cancer care. Support Care Cancer 11:278–285

    PubMed  Google Scholar 

  5. Coyne JC, Palmer SC, Shapiro PJ, Thompson R, DeMichele A (2004) Distress, psychiatric morbidity, and prescriptions for psychotropic medication in a breast cancer waiting room sample. Gen Hosp Psychiatry 26:121–128

    Article  PubMed  Google Scholar 

  6. MacDonald RN, Hugi MR, Graydon JE, Beaulieu M-D, Caines J, Firth LA et al (1998) The management of chronic pain in patients with breast cancer. The steering committee on clinical practice guidelines for the care and treatment of breast cancer. CMAJ 158 (Suppl 3):S71–S81

    Google Scholar 

  7. Bordeleau L, Pritchard K, Goodwin P, Loprinzi C (2007) Therapeutic options for the management of hot flashes in breast cancer survivors: An evidence-based review. Clin Ther 29:230–241

    Article  PubMed  CAS  Google Scholar 

  8. Ganz PA (2001) Impact of tamoxifen adjuvant therapy on symptoms, functioning, and quality of life. J Natl Cancer Inst Monogr 2001:130–134

    Google Scholar 

  9. Love RR, Cameron L, Connell BL, Leventhal H (1991) Symptoms associated with tamoxifen treatment in postmenopausal women. Arch Intern Med 151:1842–1847

    Article  PubMed  CAS  Google Scholar 

  10. Brandes LJ, Arron RJ, Bogdanovic RP, Tong J, Zaborniak CL, Hogg GR et al (1992) Stimulation of malignant growth in rodents by antidepressant drugs at clinically relevant doses. Cancer Res 52:3796–3800

    PubMed  CAS  Google Scholar 

  11. Brandes LJ, Bogdanovic RP, Cawker MD, LaBella FS (1987) Histamine and growth: interaction of antiestrogen binding site ligands with a novel histamine site that may be associated with calcium channels. Cancer Res 47:4025–4031

    PubMed  CAS  Google Scholar 

  12. Turkington RW (1972) Prolactin secretion in patients treated with various drugs: phenothiazines, tricyclic antidepressants, reserpine, and methyldopa. Arch Intern Med 130:349–354

    Article  PubMed  CAS  Google Scholar 

  13. Krulich L (1975) The effect of a serotonin uptake inhibitor (Lilly 110140) on the sercretion of prolactin in the rat. Life Sci 17:1141–1144

    Article  PubMed  CAS  Google Scholar 

  14. Urban RJ, Veldhuis JD (1991) A selective serotonin reuptake inhibitor, fluoxetine hydrochloride, modulates the pulsatile release of prolactin in postmenopausal women. Am J Obstet Gynecol 164:147–152

    PubMed  CAS  Google Scholar 

  15. Leatherman ME, Ekstrom RD, Corrigan M, Carson SW, Mason G, Golden RN (1993) Central serotonergic changes following antidepressant treatment: a neuroendocrine assessment. Psychopharmacol Bull 29:149–154

    PubMed  CAS  Google Scholar 

  16. Eisen JN, Irwin J, Quay J, Livnat S (1989) The effect of antidepressants on immune function in mice. Biol Psychiatry 26:805–817

    Article  PubMed  CAS  Google Scholar 

  17. Laudenslager ML, Clarke AS (2000) Antidepressant treatment during social challenge prior to 1 year of age affects immune and endocrine responses in adult macaques. Psychiatry Res 95:25–34

    Article  PubMed  CAS  Google Scholar 

  18. Bahl S, Cotterchio M, Kreiger N (2003) Use of antidepressant medications and the possible association with breast cancer risk. A review. Psychother Psychosom 72:185–194

    Article  PubMed  Google Scholar 

  19. Chien C, Li CI, Heckbert SR, Malone KE, Boudreau DM, Daling JR (2006) Antidepressant use and breast cancer risk. Breast Cancer Res Treat 95:131–140

    Article  PubMed  Google Scholar 

  20. Coogan PF, Palmer JR, Strom BL, Rosenberg L (2005) Use of selective serotonin reuptake inhibitors and the risk of breast cancer. Am J Epidemiol 162:835–838

    Article  PubMed  Google Scholar 

  21. Fulton-Kehoe D, Rossing MA, Rutter C, Mandelson MT, Weiss NS (2006) Use of antidepressant medications in relation to the incidence of breast cancer. Br J Cancer 94:1071–1078

    Article  PubMed  CAS  Google Scholar 

  22. Gonzalez-Perez A, Garcia Rodriguez LA (2005) Breast cancer risk among users of antidepressant medications. Epidemiology 16:101–105

    Article  PubMed  Google Scholar 

  23. Lawlor DA, Juni P, Ebrahim S, Egger M (2003) Systematic review of the epidemiologic and trial evidence of an association between antidepressant medication and breast cancer. J Clin Epidemiol 56:155–163

    Article  PubMed  Google Scholar 

  24. Goetz MP, Knox SK, Suman VJ, Rae JM, Safgren SL, Ames MM et al (2007) The impact of cytochrome P450 2D6 metabolism in women receiving adjuvant tamoxifen. Breast Cancer Res Treat 101:113–121

    Article  PubMed  CAS  Google Scholar 

  25. Lehmann D, Nelsen J, Ramanath V, Newman N, Duggan D, Smith A (2004) Lack of attenuation in the antitumor effect of tamoxifen by chronic CYP isoform inhibition. J Clin Pharmacol 44:861–865

    Article  PubMed  CAS  Google Scholar 

  26. Steingart AB, Cotterchio M (1995) Do antidepressants cause, promote, or inhibit cancers? J Clin Epidemiol 48:1407–1412

    Article  PubMed  CAS  Google Scholar 

  27. Stearns V, Johnson MD, Rae JM, Morocho A, Novielli A, Bhargava P et al (2003) Active tamoxifen metabolite plasma concentrations after coadministration of tamoxifen and the selective serotonin reuptake inhibitor paroxetine. J Natl Cancer Inst 95:1758–1764

    PubMed  CAS  Google Scholar 

  28. Jin Y, Desta Z, Stearns V, Ward B, Ho H, Lee KH et al (2005) CYP2D6 genotype, antidepressant use, and tamoxifen metabolism during adjuvant breast cancer treatment. J Natl Cancer Inst 97:30–39

    Article  PubMed  CAS  Google Scholar 

  29. Borges S, Desta Z, Li L, Skaar TC, Ward BA, Nguyen A et al (2006) Quantitative effect of CYP2D6 genotype and inhibitors on tamoxifen metabolism: implication for optimization of breast cancer treatment. Clin Pharmacol Ther 80:61–74

    Article  PubMed  CAS  Google Scholar 

  30. Goetz MP, Rae JM, Suman VJ, Safgren SL, Ames MM, Visscher DW et al (2005) Pharmacogenetics of tamoxifen biotransformation is associated with clinical outcomes of efficacy and hot flashes. J Clin Oncol 23:9312–9318

    Article  PubMed  CAS  Google Scholar 

  31. Hemeryck A, Belpaire FM (2002) Selective serotonin reuptake inhibitors and cytochrome P-450 mediated drug-drug interactions: an update. Curr Drug Metab 3:13–37

    Article  PubMed  CAS  Google Scholar 

  32. Saunders KW, Davis RL, Stergachis A (2005) Group health cooperative. In: Strom BL (ed) Pharmacoepidemiology. 4th edn. Wiley, Chichester

  33. National Cancer Institute. Surveillance, epidemiology, and end results. http://seer.cancer.gov/

  34. Fleming ID, Cooper JS, Henson DE, Hutter RVP, Kennedy BJ, Murphy GP et al (1997) AJCC cancer staging manual, 5th edn. Lippincott Williams & Wilkins, Philadelphia

  35. Enger SM, Thwin SS, Buist DS, Field T, Frost F, Geiger AM et al (2006) Breast cancer treatment of older women in integrated health care settings. J Clin Oncol 24:4377–4383

    Article  PubMed  Google Scholar 

  36. Geiger AM, Thwin SS, Lash TL, Buist DS, Prout MN, Wei F et al (2007) Recurrences and second primary breast cancers in older women with initial early-stage disease. Cancer 109:966–974

    Article  PubMed  Google Scholar 

  37. Buist DSM, Ichikawa L, Prout MN, Ulcickas Yood M, Field TS, Owusu C et al (2007) Receipt of primary breast cancer therapy and adjuvant therapy are not associated with obesity in older women with access to health care. J Clin Oncol 25:3428–3436

    Article  PubMed  Google Scholar 

  38. Thwin SS, Clough-Gorr KM, McCarty MC, Lash TL, Alford SH, Buist DS et al (2007) Automated inter-rater reliability assessment and electronic data collection in a multi-center breast cancer study. BMC Med Res Methodol 7:23

    Article  PubMed  Google Scholar 

  39. ICD-9-CM (2006) International classification of diseases, 9th Revision: Clinical Modification. Available via 6th STAT!Ref Online Electronic Medical Library

  40. World Health Organization. (2007) International statistical classification of diseases and related health problems 10th Revision. http://www.who.int/classifications/apps/icd/icd10online/. Cited June 9, 2007

  41. Rossing MA, Scholes D, Cushing-Haugen KL, Voigt LF (2000) Cimetidine use and risk of prostate and breast cancer. Cancer Epidemiol Biomarkers Prev 9:319–323

    PubMed  CAS  Google Scholar 

  42. O’Meara ES, Rossing MA, Daling JR, Elmore JG, Barlow WE, Weiss NS (2001) Hormone replacement therapy after a diagnosis of breast cancer in relation to recurrence and mortality. J Natl Cancer Inst 93:754–762

    Article  PubMed  CAS  Google Scholar 

  43. Dublin S, Rossing MA, Heckbert SR, Goff BA, Weiss NS (2002) Risk of epithelial ovarian cancer in relation to use of antidepressants, benzodiazepines, and other centrally acting medications. Cancer Causes Control 13:35–45

    Article  PubMed  Google Scholar 

  44. Buist DS, Newton KM, Miglioretti DL, Beverly K, Connelly MT, Andrade S et al (2004) Hormone therapy prescribing patterns in the United States: prevalence and rates of initiation and discontinuation, 1999–2002. Obstet Gynecol 104:1042–1050

    PubMed  Google Scholar 

  45. Smith NL, Heckbert SR, Lemaitre RN, Reiner AP, Lumley T, Weiss NS et al (2004) Esterified estrogens and conjugated equine estrogens and the risk of venous thrombosis. JAMA 292:1581–1587

    Article  PubMed  CAS  Google Scholar 

  46. Kalbfleisch JD, Prentice RL. (2002) The statistical analysis of failure time data, 2nd edn. Wiley, Chichester

  47. Charlson ME, Pompei P, Ales KL, MacKenzie CR (1987) A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis 40:373–383

    Article  PubMed  CAS  Google Scholar 

  48. Cotterchio M, Kreiger N, Darlington G, Steingart A (2000) Antidepressant medication use and breast cancer risk. Am J Epidemiol 151:951–957

    PubMed  CAS  Google Scholar 

  49. Davis S, Mirick DK (2007) Medication use and the risk of breast cancer. Eur J Epidemiol 22:319–325

    Article  PubMed  Google Scholar 

  50. Danielson DA, Jick H, Hunter JR, Stergachis A, Madsen S (1982) Nonestrogenic drugs and breast cancer. Am J Epidemiol 116:329–332

    PubMed  CAS  Google Scholar 

  51. Haque R, Enger SM, Chen W, Petitti DB (2005) Breast cancer risk in a large cohort of female antidepressant medication users. Cancer Lett 221:61–65

    Article  PubMed  CAS  Google Scholar 

  52. Kato I, Zeleniuch-Jacquotte A, Toniolo PG, Akhmedkhanov A, Koenig K, Shore RE (2000) Psychotropic medication use and risk of hormone-related cancers: the New York University Women’s Health Study. J Public Health Med 22:155–160

    Article  PubMed  CAS  Google Scholar 

  53. Kelly JP, Rosenberg L, Palmer JR, Rao RS, Strom BL, Stolley PD et al (1999) Risk of breast cancer according to use of antidepressants, phenothiazines, and antihistamines. Am J Epidemiol 150:861–868

    PubMed  CAS  Google Scholar 

  54. Kreiger N, Cotterchio M, Steingart A, Buchan G (2000) Antidepressant medication use and breast cancer. Am J Epidemiol 151:S27

    Google Scholar 

  55. Moorman PG, Grubber JM, Millikan RC, Newman B (2003) Antidepressant medications and their association with invasive breast cancer and carcinoma in situ of the breast. Epidemiology 14:307–314

    Article  PubMed  Google Scholar 

  56. Sharpe CR, Collet JP, Belzile E, Hanley JA, Boivin JF (2002) The effects of tricyclic antidepressants on breast cancer risk. Br J Cancer 86:92–97

    Article  PubMed  CAS  Google Scholar 

  57. Steingart A, Cotterchio M, Kreiger N, Sloan M (2003) Antidepressant medication use and breast cancer risk: a case-control study. Int J Epidemiol 32:961–966

    Article  PubMed  Google Scholar 

  58. Wallace RB, Sherman BM, Bean JA (1982) A case-control study of breast cancer and psychotropic drug use. Oncology 39:279–283

    Article  PubMed  CAS  Google Scholar 

  59. Csizmadi I, Collet JP, Boivin JF (2005) Bias and confounding in pharmacoepidemiology. In: Strom BL (ed) Pharmacoepidemiology, 4th edn. Wiley, Chichester

    Google Scholar 

  60. Groenvold M, Petersen MA, Idler E, Bjorner JB, Fayers PM, Mouridsen HT (2007) Psychological distress and fatigue predicted recurrence and survival in primary breast cancer patients. Breast Cancer Res Treat 105:209–219

    Article  PubMed  Google Scholar 

  61. Goodwin PJ, Ennis M, Bordeleau LJ, Pritchard KI, Trudeau ME, Koo J et al (2004) Health-related quality of life and psychosocial status in breast cancer prognosis: analysis of multiple variables. J Clin Oncol 22:4184–4192

    Article  PubMed  Google Scholar 

  62. Watson M, Homewood J, Haviland J, Bliss JM (2005) Influence of psychological response on breast cancer survival: 10-year follow-up of a population-based cohort. Eur J Cancer 41:1710–1714

    Article  PubMed  CAS  Google Scholar 

  63. Rock CL, Demark-Wahnefried W (2002) Nutrition and survival after the diagnosis of breast cancer: a review of the evidence. J Clin Oncol 20:3302–3316

    Article  PubMed  Google Scholar 

  64. Kushi LH, Kwan ML, Lee MM, Ambrosone CB (2007) Lifestyle factors and survival in women with breast cancer. J Nutr 137:236S–242S

    PubMed  CAS  Google Scholar 

  65. Weiss SR, McFarland BH, Burkhart GA, Ho PT (1998) Cancer recurrences and secondary primary cancers after use of antihistamines or antidepressants. Clin Pharmacol Ther 63:594–599

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We would like to thank Rebecca Silliman, MD, PhD for developing the data abstraction instrument, leading the BOW study, helping to secure funding and providing guidance throughout the project; and Soe Soe Thwin, PhD for developing the data abstraction instrument and sharing common programs from BOW. We would also like to thank project manager Linda Shultz, MPH and our colleagues who collected data for this study: Kristin Delaney, MPH; Margaret Farrell-Ross, MPH; Mary Sunderland; Millie Magner; Beth Kirlin, Srabani Dutta, Chester Pabiniak, and Julia Hecht, PhD. This research was supported by: National Cancer Institute (R01 CA09377, T32 CA09168 to JC); American Cancer Society (CRTG-03–024-01-CCE). The contents of this publication are soley the responsibility of the authors and do not necessarily represent the official views of the NCI, NIH.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Jessica Chubak.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Chubak, J., Buist, D.S.M., Boudreau, D.M. et al. Breast cancer recurrence risk in relation to antidepressant use after diagnosis. Breast Cancer Res Treat 112, 123–132 (2008). https://doi.org/10.1007/s10549-007-9828-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10549-007-9828-9

Keywords

Navigation