Influence of the competing risk of death on estimates of disease recurrence in trials of adjuvant endocrine therapy for early-stage breast cancer: A secondary analysis of MA.27, MA.17 and MA.17R. (May 2021)

• Record Type: Journal Article
• Authors: Ethier, Josee-Lyne; Anderson, Geoffrey M.; Austin, Peter C.; Clemons, Mark; Parulekar, Wendy; Shepherd, Lois; Summers Trasiewicz, Lily; Tu, Dongsheng; Amir, Eitan
• Is Part Of: European journal of cancer. Volume 149(2021)
• Page Start: 117
• Page End: 127
• Publication Date: 2021-05
• Subjects: Breast cancer -- Aromatase inhibitors -- Randomised controlled trial -- Clinical trial -- Letrozole -- Exemestane -- Anastrozole -- Mortality -- Recurrence; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Cancer; Tumors; Electronic journals; Periodicals; Electronic journals; 616.994
• DOI: 10.1016/j.ejca.2021.02.034
• Languages: English
• ISSNs: 0959-8049

Abstract

Abstract: Background: Many women diagnosed with early-stage hormone-sensitive breast cancer die of causes other than their breast cancer. These competing risks can create challenges in analysing and clearly communicating data on risk of breast cancer recurrence or death. Here, we quantify the impact of competing risks on estimates of disease recurrence and benefit from therapy. Patients and methods: Using data from the MA.27, MA.17 and MA.17R trials of adjuvant endocrine therapy in early breast cancer, we compared Kaplan-Meier (KM) and competing risk methods for disease-free survival (DFS) and distant recurrence-free survival (DRFS). Each trial was analysed separately. In KM analyses, participants were censored at the time of non-breast cancer death. Competing risk analyses comprised cumulative incidence functions in which non-breast cancer death was a competing risk. Results: Non-breast cancer deaths were observed more often in older participants, in those with lower risk of breast cancer and after longer follow-up. Compared with conventional analyses, estimates of the proportion of participants with DFS or DRFS events were lower in competing risk analyses, with this difference increasing over the course of follow-up. The absolute treatment benefit was similar or modestly lower in competing risk analyses. Conclusion: Compared with KM methods, competing risk analyses result in lower estimates of DFS and DRFS events and similar or modestly lower absolute benefit from experimental endocrine therapy. Over a long time horizon, competing risk methods may be preferable to KM methods when estimating future risk of recurrence in early-stage hormone-sensitive breast cancer. Clinical trials registration: Clinicaltrials.gov ; NCT00003140, NCT00754845, NCT00066573 . Highlights: This is a secondary analysis of large adjuvant endocrine therapy trials (MA.17, MA.17R and MA.27). Estimates of treatment outcomes were compared using conventional and competing risk methods. The proportion of patients with recurrence events was lower in competing risk analyses. Absolute treatment benefit was similar or modestly lower in competing risk analyses. Competing risk methods may provide an optimal strategy to estimate long-term outcomes.