title: Time dependent effects of adjuvant tamoxifen therapy on cerebrovascular disease: results from a randomised trial.
abstract: BACKGROUND
  Tamoxifen has been associated with an increased risk of stroke. There is, however, little information on the effect in the post-treatment period. Using data from the Swedish Breast Cancer Group adjuvant trial of 5 vs 2 years of tamoxifen treatment, we now report both short-term and long-term effects on morbidity as well as mortality because of cerebrovascular disease.
  
  
  METHODS
  Data from the Swedish National Hospital Discharge Registry combined with information from the Swedish Cause of Death Registry was used to define events of disease. Hazard ratios (HRs) were estimated using Cox regression.
  
  
  RESULTS
  Comparing patients randomised to 5 years of tamoxifen with patients randomised to 2 years of tamoxifen, the incidence of cerebrovascular diseases was increased (HR 1.70, 95% CI 1.05-2.75) during the active treatment phase and reduced after the active treatment period (HR 0.78, 95% CI 0.63-0.96), and the difference in HR between the two time-periods was significant (P=0.0033). The mortality from cerebrovascular diseases was increased during the treatment period (HR 3.18, 95% CI 1.03-9.87) and decreased during the post-treatment period (HR 0.60, 95% CI 0.40-0.90) with a significant difference in HR between the two periods of follow-up (P=0.0066). Similar results were seen for subgroups of cerebrovascular diseases, such as stroke and ischaemic stroke.
  
  
  CONCLUSIONS
  In an adjuvant setting, tamoxifen was associated with an increased risk of cerebrovascular disease during treatment, but a decreased risk in the post-treatment period.
authors.affiliation: Oncologic center, Linköping University Hospital, S-581 85 Linköping, Sweden. johan.rosell@lio.se
authors.forename: J
authors.initials: J
authors.lastname: Rosell
authors.forename: B
authors.initials: B
authors.lastname: Nordenskjöld
authors.forename: N-O
authors.initials: NO
authors.lastname: Bengtsson
authors.forename: T
authors.initials: T
authors.lastname: Fornander
authors.forename: T
authors.initials: T
authors.lastname: Hatschek
authors.forename: H
authors.initials: H
authors.lastname: Lindman
authors.forename: P-O
authors.initials: PO
authors.lastname: Malmström
authors.forename: A
authors.initials: A
authors.lastname: Wallgren
authors.forename: O
authors.initials: O
authors.lastname: Stål
authors.forename: J
authors.initials: J
authors.lastname: Carstensen
mesh_terms: D000328:Adult; D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000453:epidemiology; D002277:Carcinoma / Q000150:complications / Q000188:drug therapy* / Q000453:epidemiology; D002561:Cerebrovascular Disorders / Q000453:epidemiology* / Q000209:etiology; D017024:Chemotherapy, Adjuvant; D015897:Comorbidity; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data*; D012307:Risk Factors; D013548:Sweden / Q000453:epidemiology; D013629:Tamoxifen / Q000494:pharmacology / Q000627:therapeutic use*; D013997:Time Factors
chemical_list: D018931:Antineoplastic Agents, Hormonal; D013629:Tamoxifen