Cause-specific mortality in long-term survivors of breast cancer: A 25-year follow-up study

Int J Radiat Oncol Biol Phys. 2006 Mar 15;64(4):1081-91. doi: 10.1016/j.ijrobp.2005.10.022. Epub 2006 Jan 30.

Abstract

Purpose: To assess long-term cause-specific mortality in breast cancer patients.

Patients and 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).

Conclusion: 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.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Breast Neoplasms / mortality*
  • Breast Neoplasms / radiotherapy
  • Breast Neoplasms / surgery
  • Cardiovascular Diseases / etiology
  • Cardiovascular Diseases / mortality*
  • Cause of Death
  • Cyclophosphamide / administration & dosage
  • Cyclophosphamide / adverse effects
  • Female
  • Fluorouracil / administration & dosage
  • Fluorouracil / adverse effects
  • Follow-Up Studies
  • Humans
  • Mastectomy
  • Methotrexate / administration & dosage
  • Methotrexate / adverse effects
  • Middle Aged
  • Neoplasms, Second Primary / mortality*
  • Netherlands
  • Proportional Hazards Models
  • Risk
  • Survivors*

Substances

  • Cyclophosphamide
  • Fluorouracil
  • Methotrexate

Supplementary concepts

  • CMF regimen