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 (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.