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

Eur J Cancer. 2014 Sep;50(13):2201-10. doi: 10.1016/j.ejca.2014.04.033. Epub 2014 Jun 18.

Abstract

Aim of the study: 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.

Conclusion: 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.

Keywords: Breast cancer; Cause of death; Cerebrovascular disease; Heart disease; Radiotherapy; Side-effect.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Alkylating / administration & dosage*
  • Breast Neoplasms / epidemiology
  • Breast Neoplasms / mortality*
  • Breast Neoplasms / radiotherapy*
  • Breast Neoplasms / therapy
  • Cardiovascular Diseases / epidemiology
  • Cardiovascular Diseases / mortality*
  • Cerebrovascular Disorders / epidemiology
  • Cerebrovascular Disorders / mortality*
  • Combined Modality Therapy
  • Cyclophosphamide / administration & dosage*
  • Female
  • Humans
  • Mastectomy
  • Middle Aged
  • Neoplasm Recurrence, Local / epidemiology
  • Neoplasm Recurrence, Local / mortality
  • Neoplasm Staging
  • Postmenopause
  • Sweden / epidemiology

Substances

  • Antineoplastic Agents, Alkylating
  • Cyclophosphamide