Competing causes of death from a randomized trial of extended adjuvant endocrine therapy for breast cancer

J Natl Cancer Inst. 2008 Feb 20;100(4):252-60. doi: 10.1093/jnci/djn014. Epub 2008 Feb 12.

Abstract

Background: Older women with early-stage breast cancer experience higher rates of non-breast cancer-related death. We examined factors associated with cause-specific death in a large cohort of breast cancer patients treated with extended adjuvant endocrine therapy.

Methods: In the MA.17 trial, conducted by the National Cancer Institute of Canada Clinical Trials Group, 5170 breast cancer patients (median age = 62 years; range = 32-94 years) who were disease free after approximately 5 years of adjuvant tamoxifen treatment were randomly assigned to treatment with letrozole (2583 women) or placebo (2587 women). The median follow-up was 3.9 years (range 0-7 years). We investigated the association of 11 baseline factors with the competing risks of death from breast cancer, other malignancies, and other causes. All statistical tests were two-sided likelihood ratio criterion tests.

Results: During follow-up, 256 deaths were reported (102 from breast cancer, 50 from other malignancies, 100 from other causes, and four from an unknown cause). Non-breast cancer deaths accounted for 60% of the 252 known deaths (72% for those > or = 70 years and 48% for those < 70 years). Two baseline factors were differentially associated with type of death: cardiovascular disease was associated with a statistically significant increased risk of death from other causes (P.002), and osteoporosis was associated with a statistically significant increased risk of death from other malignancies (P.05). An increased risk of breast cancer-specific death was associated with lymph node involvement (P < .001). Increased risk of death from all three causes was associated with older age (P < .001).

Conclusions: Non-breast cancer-related deaths were more common than breast cancer-specific deaths in this cohort of 5-year breast cancer survivors, especially among older women.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Aged
  • Antineoplastic Agents, Hormonal / therapeutic use*
  • Breast Neoplasms / chemistry
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / mortality*
  • Canada / epidemiology
  • Cardiovascular Diseases / mortality
  • Cause of Death*
  • Chemotherapy, Adjuvant
  • Disease-Free Survival
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • Humans
  • Letrozole
  • Middle Aged
  • Neoplasms, Hormone-Dependent / drug therapy
  • Neoplasms, Hormone-Dependent / mortality
  • Nitriles / therapeutic use*
  • Osteoporosis, Postmenopausal / mortality
  • Prospective Studies
  • Receptors, Estrogen / analysis
  • Receptors, Progesterone / analysis
  • Research Design
  • Risk Factors
  • Triazoles / therapeutic use*

Substances

  • Antineoplastic Agents, Hormonal
  • Nitriles
  • Receptors, Estrogen
  • Receptors, Progesterone
  • Triazoles
  • Letrozole