title: Cause-specific mortality in long-term survivors of breast cancer: A 25-year follow-up study.
abstract: OBJECTIVE
  To assess long-term cause-specific mortality in breast cancer patients.
  
  
  METHODS
  We studied mortality in 7425 patients treated for early breast cancer between 1970 and 1986. Follow-up was 94% complete until January 2000. Treatment-specific mortality was evaluated by calculating standardized mortality ratios (SMRs) based on comparison with general population rates and by using Cox proportional hazards regression.
  
  
  RESULTS
  After a median follow-up of 13.8 years, 4160 deaths were observed, of which 76% were due to breast cancer. Second malignancies showed a slightly increased SMR of 1.2 (95% confidence interval [CI], 1.0-1.3). Radiotherapy (RT) as compared with surgery was associated with a 1.7-fold (95% CI, 1.2-2.5) increased mortality from cardiovascular disease (CVD). After postlumpectomy RT, no increased mortality from CVD was observed (hazard ratio, 1.0; 95% CI, 0.5-1.9). Postmastectomy RT administered before 1979 and between 1979 and 1986 was associated with a 2-fold (95% CI, 1.2-3.4) and 1.5-fold (95% CI, 0.9-2.7) increase, respectively. Patients treated before age 45 experienced a higher SMR (2.0) for both solid tumors (95% CI, 1.6-2.7) and CVD (95% CI, 1.3-3.1).
  
  
  CONCLUSIONS
  Currently, a large population of breast cancer survivors is at increased risk of death from CVDs and second cancers, especially when treated with RT at a young age. Patients irradiated after 1979 experience low (postmastectomy RT) or no (postlumpectomy RT) excess mortality from CVD.
authors.affiliation: Department of Epidemiology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Maartje J
authors.initials: MJ
authors.lastname: Hooning
authors.forename: Berthe M P
authors.initials: BM
authors.lastname: Aleman
authors.forename: Agnes J M
authors.initials: AJ
authors.lastname: van Rosmalen
authors.forename: Marianne A
authors.initials: MA
authors.lastname: Kuenen
authors.forename: Jan G M
authors.initials: JG
authors.lastname: Klijn
authors.forename: Flora E
authors.initials: FE
authors.lastname: van Leeuwen
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000401:mortality* / Q000532:radiotherapy / Q000601:surgery; D002318:Cardiovascular Diseases / Q000209:etiology / Q000401:mortality*; D002423:Cause of Death; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D005500:Follow-Up Studies; D006801:Humans; D008408:Mastectomy; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D016609:Neoplasms, Second Primary / Q000401:mortality*; D009426:Netherlands; D016016:Proportional Hazards Models; D012306:Risk; D017741:Survivors
chemical_list: D003520:Cyclophosphamide; D005472:Fluorouracil; D008727:Methotrexate