Journal of the National Cancer Institute Advance Access originally published online on February 12, 2008
JNCI Journal of the National Cancer Institute 2008 100(4):252-260; doi:10.1093/jnci/djn014
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© The Author 2008. Published by Oxford University Press.
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Competing Causes of Death From a Randomized Trial of Extended Adjuvant Endocrine Therapy for Breast Cancer
Affiliations of authors: National Cancer Institute of Canada Clinical Trials Group, Queen's University, Kingston, ON, Canada (JAWC, DM, LS, WP, MP, CY); Department of Oncology, Mayo Clinic, Rochester, MN (JNI); Department of Medicine, Vermont Cancer Center, Burlington, VT (HBM); Department of Hematology and Oncology, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA (PEG)
Correspondence to: Judith-Anne W. Chapman, PhD, National Cancer Institute of Canada Clinical Trials Group, Queen's University, 10 Stuart St, Kingston, ON, Canada (e-mail: jchapman{at}ctg.queensu.ca).
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 (range0–7 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 
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.
| CONTEXT AND CAVEATS Prior knowledge Deaths of older women diagnosed with breast cancer are often due to causes other than breast cancer. Study design Prospective study of data from a large randomized trial of breast cancer patients treated with extended adjuvant endocrine therapy. Contribution Deaths from non–breast cancer causes were more common than breast cancer–related deaths, especially in older women. Cardiovascular disease at baseline was associated with a statistically significant increased risk of death from other causes. Osteoporosis at baseline was associated with increased risk of death from other malignancies. Implications Medical attention to the potential for death from other causes becomes increasingly important in older patients with breast cancer. Limitations The patient population was not representative of all breast cancer patients; it contained patients with hormone receptor–positive disease who were at low risk of recurrence and were disease free after 5 years of tamoxifen treatment. Younger women, who tend to have hormone-receptor negative disease and shorter survival, were excluded from this trial.
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The reviewers’ and Senior Editor's input was appreciated and greatly helped to improve the exposition of this work. The authors acknowledge the dedicated work of those who contributed to the NCIC CTG MA.17 trial; the international trialists; clinicians who enrolled patients; clinical research associates who acquired the data; NCIC CTG computer systems group, especially Liting Zhu; and most of all the patients who participated in the trial.
The authors had full responsibility for the design of the study, collection of the data, the analysis and interpretation of the data, the decision to submit the manuscript for publication, and the writing of the manuscript.
Editor’s note: Dr J. N. Ingle received honoria from Novartis for consulting and for speaking. Dr P. E. Goss received consulting honoria from Novartis, Pfizer, and AstraZeneca.
Manuscript received June 11, 2007; revised December 4, 2007; accepted January 10, 2008.
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J Natl Cancer Inst 2008 100: 230-231.
J Natl Cancer Inst 2008 100: 227.
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