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.
Aged
Antineoplastic Agents, Hormonal
/ adverse effects
Breast Neoplasms
/ drug therapy
Cause of Death
Chemotherapy, Adjuvant
Disease Progression
Disease-Free Survival
Female
Humans
Middle Aged
Neoplasm Recurrence, Local
Neoplasm Staging
Randomized Controlled Trials as Topic
Risk Assessment
Risk Factors
Time Factors
Anastrozole
Aromatase inhibitors
Breast cancer
Clinical trial
Exemestane
Letrozole
Mortality
Randomised controlled trial
Recurrence
Journal
European journal of cancer (Oxford, England : 1990)
ISSN: 1879-0852
Titre abrégé: Eur J Cancer
Pays: England
ID NLM: 9005373
Informations de publication
Date de publication:
05 2021
05 2021
Historique:
received:
09
11
2020
revised:
17
02
2021
accepted:
22
02
2021
pubmed:
15
4
2021
medline:
21
10
2021
entrez:
14
4
2021
Statut:
ppublish
Résumé
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. 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. 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. 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. Clinicaltrials.gov; NCT00003140, NCT00754845, NCT00066573.
Sections du résumé
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.
Identifiants
pubmed: 33853037
pii: S0959-8049(21)00142-8
doi: 10.1016/j.ejca.2021.02.034
pii:
doi:
Substances chimiques
Antineoplastic Agents, Hormonal
0
Banques de données
ClinicalTrials.gov
['NCT00066573', 'NCT00003140', 'NCT00754845']
Types de publication
Comparative Study
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
117-127Informations de copyright
Copyright © 2021 Elsevier Ltd. All rights reserved.
Déclaration de conflit d'intérêts
Conflict of interest statement E.A. reports personal fees from Genentech/Roche, personal fees from Sandoz, personal fees from Apobiologix and personal fees from Agendia, outside the submitted work (no direct conflict with this research/manuscript). J.-L.E. reports personal fees from AstraZeneca and personal fees from Merck, outside the submitted work (no direct conflict with this research/manuscript). G.M.A., P.C.A., M.C., W.P., L.S., L.S.T. and D.T. have nothing to declare.