Summary
Background
Antidepressants are among the most commonly prescribed drugs in the United States. Laboratory studies suggest that because certain antidepressants increase prolactin levels that they may also increase breast cancer risk. However, human studies evaluating use of antidepressants in relation to breast cancer risk have yielded inconsistent results.
Methods
A population-based case-control study consisting of 975 breast cancer cases 65–79 years of age diagnosed from 1997–1999 and 1007 age and residence-matched controls was conducted in western Washington State. Detailed information on antidepressant use was obtained through structured in-person interviews. Logistic regression was performed to analyze the relationship between antidepressant use and breast cancer risk.
Results
Overall, there was no association between ever use of antidepressants and breast cancer risk (odds ratio [OR] = 1.2, 95% confidence interval [95% CI]: 0.9–1.6). When evaluated separately, tricyclic antidepressants (TCA), selective serotonin reuptake inhibitors (SSRI), and triazolopyridines were each not associated with breast cancer risk. However, risk varied by hormone receptor status. Compared to never users, ever users of SSRIs had elevated risks of progesterone receptor (PR) negative and estrogen receptor (ER) positive/PR-negative breast cancers (OR = 1.8, 95% CI: 1.1–3.6 and OR = 2.0, 95% CI: 1.1–3.8, respectively), but not of tumors with other hormone receptor profiles.
Conclusions
Based on these results and those of previous studies, there is limited evidence that any type of antidepressant use is associated with breast cancer risk overall. SSRIs may elevate risks of PR- and ER+/PR- tumors, though further studies are needed to confirm these associations.
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References
Top 200 Drugs of 2002 [http://www.pharmacytimes.com/article.cfm?ID=338]
Stafford RS, MacDonald EA, Finkelstein SN, 2001. National patterns of medication treatment for depression, 1987 to 2001 Prim Care Companion J Clin Psychiat 3:232–235
Ohayon MM, Lader MH, 2002. Use of psychotropic medication in the general population of France, Germany, Italy, and the United Kingdom J Clin Psychiat 63: 817–825
Brandes LJ, Arron RJ, Bogdanovic RP, Tong J, Zaborniak CL, Hogg GR, Warrington RC, Fang W, LaBella FS, 1992. Stimulation of malignant growth in rodents by antidepressant drugs at clinically relevant doses Cancer Res 52: 3796–3800
Hilakivi-Clarke L, Wright A, Lippman ME, 1993. DMBA-induced mammary tumor growth in rats exhibiting increased or decreased ability to cope with stress due to early postnatal handling or antidepressant treatment Physiol Behav 54: 229–236
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
Cowen PJ, Sargent PA, 1997. Changes in plasma prolactin during SSRI treatment: evidence for a delayed increase in 5-HT neurotransmission J Psychopharmacol 11: 345–348
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
Kiss R, de Launoit Y, L’Hermite-Baleriaux M, L’Hermite M, Paridaens RJ, Danguy AJ, Pasteels JL, 1987. Effect of prolactin and estradiol on cell proliferation in the uterus and the MXT mouse mammary neoplasm J Natl Cancer Inst 78: 993–998
Welsch CW, Nagasawa H, 1977. Prolactin and murine mammary tumorigenesis: a review Cancer Res 37: 951–963
Wang DY, De Stavola BL, Bulbrook RD, Allen DS, Kwa HG, Fentiman IS, Hayward JL, Millis RR, 1992. Relationship of blood prolactin levels and the risk of subsequent breast cancer Int J Epidemiol 21: 214–221
Kabuto M, Akiba S, Stevens RG, Neriishi K, Land CE, 2000. A prospective study of estradiol and breast cancer in Japanese women Cancer Epidemiol Biomarkers Prev 9: 575–579
Hankinson SE, Willett WC, Michaud DS, Manson JE, Colditz GA, Longcope C, Rosner B, Speizer FE, 1999. Plasma prolactin levels and subsequent risk of breast cancer in postmenopausal women J Natl Cancer Inst 91: 629–634
Tworoger SS, Eliassen AH, Rosner B, Sluss P, Hankinson SE, 2004. Plasma prolactin concentrations and risk of postmenopausal breast cancer Cancer Res 64: 6814–6819
Hermann B, Vollmer I, Holsboer F, Rupprecht R, 2001. Antidepressants do not modulate estrogen receptor alpha-mediated gene expression J Neural Transm 108: 1197–1202
Kuiper GG, Shughrue PJ, Merchenthaler I, Gustafsson JA, 1998. The estrogen receptor beta subtype: a novel mediator of estrogen action in neuroendocrine systems Front Neuroendocrinol 19: 253–286
Laudenslager ML, Clarke AS, 2000. Antidepressant treatment during social challenge prior to 1 year of age affects immune and endocrine responses in adult macaques Psychiat Res 95: 25–34
Eisen JN, Irwin J, Quay J, Livnat S, 1989. The effect of antidepressants on immune function in mice Biol Psychiat 26: 805–817
Wang PS, Walker AM, Tsuang MT, Orav EJ, Levin R, Avorn J, 2001. Antidepressant use and the risk of breast cancer: a non-association J Clin Epidemiol 54: 728–734
Cotterchio M, Kreiger N, Darlington G, Steingart A, 2000. Antidepressant medication use and breast cancer risk Am J Epidemiol 151: 951–957
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
Gonzalez-Perez A, Garcia Rodriguez LA, 2005. Breast cancer risk among users of antidepressant medications Epidemiology 16: 101–105
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
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
Kelly JP, Rosenberg L, Palmer JR, Rao RS, Strom BL, Stolley PD, Zauber AG, Shapiro S, 1999. Risk of breast cancer according to use of antidepressants, phenothiazines, and antihistamines Am J Epidemiol 150: 861–868
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
Boudreau DM, Daling JR, Malone KE, Gardner JS, Blough DK, Heckbert SR, 2004. A validation study of patient interview data and pharmacy records for antihypertensive, statin, and antidepressant medication use among older women Am J Epidemiol 159: 308–317
Armstrong BK, White E, Saracci R: Reducing measurement error, its effects. In: Principles of Exposure Measurement in Epidemiology. Oxford University Press, Oxford, 1992, pp.115–136
Ormandy CJ, Hall RE, Manning DL, Robertson JF, Blamey RW, Kelly PA, Nicholson RI, Sutherland RL, 1997. Coexpression and cross-regulation of the prolactin receptor and sex steroid hormone receptors in breast cancer J Clin Endocrinol Metab 82: 3692–3699
Gutzman JH, Miller KK, Schuler LA, 2004. Endogenous human prolactin and not exogenous human prolactin induces estrogen receptor alpha and prolactin receptor expression and increases estrogen responsiveness in breast cancer cells J Steroid Biochem Mol Biol 88: 69–77
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Chien, C., Li, C.I., Heckbert, S.R. et al. Antidepressant use and breast cancer risk. Breast Cancer Res Treat 95, 131–140 (2006). https://doi.org/10.1007/s10549-005-9056-0
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DOI: https://doi.org/10.1007/s10549-005-9056-0