title: Increased cardio and cerebrovascular mortality in breast cancer patients treated with postmastectomy radiotherapy--25 year follow-up of a randomised trial from the South Sweden Breast Cancer Group.
abstract: OBJECTIVE
  To analyse late morbidity and mortality in pre and post-menopausal breast cancer patients treated with postmastectomy radiotherapy, with emphasis on side-effects from the heart, cerebrovascular and respiratory systems.
  
  
  METHODS
  Long term follow-up of two randomised, clinical trials with 1100 patients was carried out. Pre-menopausal women were allocated to radiotherapy (RT), RT+oral cyclophosphamide (RT+C) or cyclophosphamide only (C). Post-menopausal women were allocated to RT, RT+Tamoxifen for one year (RT+Tam) or tamoxifen only (Tam). Information on admission to hospital, mortality and causes of death was obtained from national registers.
  
  
  RESULTS
  After 25 years, adding RT to cyclophosphamide in pre-menopausal women raised the mortality from heart disease from zero to 0.8% (p=0.04). In post-menopausal women, adding RT to Tam raised the mortality from heart disease from 10.5% to 18.4% (p=0.005). In post-menopausal women mortality due to cerebrovascular disease increased from 3.4% to 8.7% by adding RT to Tam (p=0.015). The differences were not evident until in the second decade of follow-up. In spite of differences in specific causes of death, there were no significant differences between the treatment arms concerning morbidity or overall mortality.
  
  
  CONCLUSIONS
  Postmastectomy radiotherapy to the chest wall and loco-regional lymph nodes including the parasternal lymph nodes as delivered in the end of the seventies did not reduce overall mortality, but gave a significantly increased risk of death from heart and cerebrovascular disease, which appeared during the second decade after radiotherapy.
authors.affiliation: Skåne Department of Oncology, Skåne University Hospital, Lund, Sweden; Department of Clinical Sciences, Division of Oncology, Lund University, Lund, Sweden. Electronic address: Fredrika.Killander@med.lu.se.
authors.forename: Fredrika
authors.initials: F
authors.lastname: Killander
authors.affiliation: Department of Cancer Epidemiology, Lund University, Lund, Sweden.
authors.forename: Harald
authors.initials: H
authors.lastname: Anderson
authors.affiliation: Skåne Department of Oncology, Skåne University Hospital, Lund, Sweden; Department of Clinical Sciences, Division of Oncology, Lund University, Lund, Sweden.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Kjellén
authors.affiliation: Skåne Department of Oncology, Skåne University Hospital, Lund, Sweden; Department of Clinical Sciences, Division of Oncology, Lund University, Lund, Sweden.
authors.forename: Per
authors.initials: P
authors.lastname: Malmström
mesh_terms: D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage*; D001943:Breast Neoplasms / Q000453:epidemiology / Q000401:mortality* / Q000532:radiotherapy* / Q000628:therapy; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000401:mortality*; D002561:Cerebrovascular Disorders / Q000453:epidemiology / Q000401:mortality*; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D008408:Mastectomy; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology / Q000401:mortality; D009367:Neoplasm Staging; D017698:Postmenopause; D013548:Sweden / Q000453:epidemiology
chemical_list: D018906:Antineoplastic Agents, Alkylating; D003520:Cyclophosphamide
keywords: Breast cancer; Cause of death; Cerebrovascular disease; Heart disease; Radiotherapy; Side-effect