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

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 = 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.