title: Tamoxifen and Antidepressant Drug Interaction in a Cohort of 16,887 Breast Cancer Survivors.
abstract: BACKGROUND
  Controversy persists about whether certain antidepressants reduce tamoxifen's effectiveness on lowering breast cancer recurrence. We investigated whether taking tamoxifen and antidepressants (in particular, paroxetine) concomitantly is associated with an increased risk of recurrence or contralateral breast cancer.
  
  
  METHODS
  We examined 16 887 breast cancer survivors (TNM stages 0-II) diagnosed between 1996 and 2007 and treated with tamoxifen in two California health plans. Women were followed-up through December 31, 2009, for subsequent breast cancer. The main exposure was the percent of days of overlap when both tamoxifen and an antidepressant (paroxetine, fluoxetine, other selective serotonin reuptake inhibitors, tricyclics, and other classes) were used. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using multivariable Cox regression models with time-varying medication variables.
  
  
  RESULTS
  Of the 16 887 women, half (n = 8099) used antidepressants and 2946 women developed subsequent breast cancer during the 14-year study period. We did not find a statistically significant increased risk of subsequent breast cancer in women who concurrently used paroxetine and tamoxifen. For 25%, 50%, and 75% increases in percent overlap days between paroxetine and tamoxifen, hazard ratios were 1.06 (95% CI = 0.98 to 1.14, P = .09), 1.13 (95% CI = 0.98 to 1.30, P = .09), and 1.20 (95% CI = 0.97 to 1.49, P = .09), respectively, in the first year of tamoxifen treatment but were not statistically significant. Hazard ratios decreased to 0.94 (95% CI = 0.81 to 1.10, P = .46), 0.89 (95% CI = 0.66 to 1.20, P = .46), and 0.85 (95% CI = 0.54 to 1.32, P = .46) by the fifth year (all non-statistically significantly). Absolute subsequent breast cancer rates were similar among women who used paroxetine concomitantly with tamoxifen vs tamoxifen-only users. For the other antidepressants, we again found no such associations.
  
  
  CONCLUSIONS
  Using the comprehensive electronic health records of insured patients, we did not observe an increased risk of subsequent breast cancer in women who concurrently used tamoxifen and antidepressants, including paroxetine.
authors.affiliation: Affiliations of authors:Kaiser Permanente Southern California , Pasadena CA (RH, JS, JES, SAA, TCC, JC, CA); Harvard Medical School and Harvard Pilgrim Health Care Institute , Boston MA (KK, SWF); Kaiser Permanente Northern California , Oakland, CA (LAH).
authors.forename: Reina
authors.initials: R
authors.lastname: Haque
authors.affiliation: Affiliations of authors:Kaiser Permanente Southern California , Pasadena CA (RH, JS, JES, SAA, TCC, JC, CA); Harvard Medical School and Harvard Pilgrim Health Care Institute , Boston MA (KK, SWF); Kaiser Permanente Northern California , Oakland, CA (LAH).
authors.forename: Jiaxiao
authors.initials: J
authors.lastname: Shi
authors.affiliation: Affiliations of authors:Kaiser Permanente Southern California , Pasadena CA (RH, JS, JES, SAA, TCC, JC, CA); Harvard Medical School and Harvard Pilgrim Health Care Institute , Boston MA (KK, SWF); Kaiser Permanente Northern California , Oakland, CA (LAH).
authors.forename: Joanne E
authors.initials: JE
authors.lastname: Schottinger
authors.affiliation: Affiliations of authors:Kaiser Permanente Southern California , Pasadena CA (RH, JS, JES, SAA, TCC, JC, CA); Harvard Medical School and Harvard Pilgrim Health Care Institute , Boston MA (KK, SWF); Kaiser Permanente Northern California , Oakland, CA (LAH).
authors.forename: Syed A
authors.initials: SA
authors.lastname: Ahmed
authors.affiliation: Affiliations of authors:Kaiser Permanente Southern California , Pasadena CA (RH, JS, JES, SAA, TCC, JC, CA); Harvard Medical School and Harvard Pilgrim Health Care Institute , Boston MA (KK, SWF); Kaiser Permanente Northern California , Oakland, CA (LAH).
authors.forename: T Craig
authors.initials: TC
authors.lastname: Cheetham
authors.affiliation: Affiliations of authors:Kaiser Permanente Southern California , Pasadena CA (RH, JS, JES, SAA, TCC, JC, CA); Harvard Medical School and Harvard Pilgrim Health Care Institute , Boston MA (KK, SWF); Kaiser Permanente Northern California , Oakland, CA (LAH).
authors.forename: Joanie
authors.initials: J
authors.lastname: Chung
authors.affiliation: Affiliations of authors:Kaiser Permanente Southern California , Pasadena CA (RH, JS, JES, SAA, TCC, JC, CA); Harvard Medical School and Harvard Pilgrim Health Care Institute , Boston MA (KK, SWF); Kaiser Permanente Northern California , Oakland, CA (LAH).
authors.forename: Chantal
authors.initials: C
authors.lastname: Avila
authors.affiliation: Affiliations of authors:Kaiser Permanente Southern California , Pasadena CA (RH, JS, JES, SAA, TCC, JC, CA); Harvard Medical School and Harvard Pilgrim Health Care Institute , Boston MA (KK, SWF); Kaiser Permanente Northern California , Oakland, CA (LAH).
authors.forename: Ken
authors.initials: K
authors.lastname: Kleinman
authors.affiliation: Affiliations of authors:Kaiser Permanente Southern California , Pasadena CA (RH, JS, JES, SAA, TCC, JC, CA); Harvard Medical School and Harvard Pilgrim Health Care Institute , Boston MA (KK, SWF); Kaiser Permanente Northern California , Oakland, CA (LAH).
authors.forename: Laurel A
authors.initials: LA
authors.lastname: Habel
authors.affiliation: Affiliations of authors:Kaiser Permanente Southern California , Pasadena CA (RH, JS, JES, SAA, TCC, JC, CA); Harvard Medical School and Harvard Pilgrim Health Care Institute , Boston MA (KK, SWF); Kaiser Permanente Northern California , Oakland, CA (LAH).
authors.forename: Suzanne W
authors.initials: SW
authors.lastname: Fletcher
authors.affiliation: Affiliations of authors:Kaiser Permanente Southern California , Pasadena CA (RH, JS, JES, SAA, TCC, JC, CA); Harvard Medical School and Harvard Pilgrim Health Care Institute , Boston MA (KK, SWF); Kaiser Permanente Northern California , Oakland, CA (LAH).
authors.forename: Marilyn L
authors.initials: ML
authors.lastname: Kwan
mesh_terms: D000328:Adult; D000368:Aged; D018687:Antidepressive Agents, Second-Generation / Q000627:therapeutic use*; D018931:Antineoplastic Agents, Hormonal / Q000037:antagonists & inhibitors* / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000453:epidemiology / Q000473:pathology / Q000517:prevention & control / Q000523:psychology; D015331:Cohort Studies; D003863:Depression / Q000188:drug therapy* / Q000209:etiology; D005260:Female; D006295:Health Resources / Q000706:statistics & numerical data; D006801:Humans; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology / Q000517:prevention & control*; D009367:Neoplasm Staging; D016017:Odds Ratio; D017374:Paroxetine / Q000627:therapeutic use*; D016016:Proportional Hazards Models; D017741:Survivors; D013629:Tamoxifen / Q000037:antagonists & inhibitors* / Q000627:therapeutic use*; D014481:United States / Q000453:epidemiology
chemical_list: D018687:Antidepressive Agents, Second-Generation; D018931:Antineoplastic Agents, Hormonal; D013629:Tamoxifen; D017374:Paroxetine