Influence of Competing Risks on Estimates of Recurrence Risk and Breast Cancer-Specific Mortality in Analyses of the Early Breast Cancer Trialists Collaborative Group

2019 ◽  
Author(s):  
Ramy Saleh ◽  
Michelle B. Nadler ◽  
Alexandra Desnoyers ◽  
Danielle L. Rodin ◽  
Husam Abdel-Qadir ◽  
...  
2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 533-533
Author(s):  
Ramy Saleh ◽  
Michelle Nadler ◽  
Alexandra Desnoyers ◽  
Danielle Lee Rodin ◽  
Husam Abdel-Qadir ◽  
...  

533 Background: Early stage breast cancer is a curable disease with the majority of patients dying of causes other than breast cancer. The influence of these competing risks of death on the interpretation of Kaplan-Meier(KM)-based analyses such as those performed by the Early Breast Cancer Trialists Collaborative Group (EBCTCG) are unknown. Methods: We searched the Clinical Trial Service Unit and Epidemiological Studies Unit website at Oxford University to identify all meta-analyses published by the EBCTCG between 2005 and 2018. Studies were included if they contained KM curves with risk estimates for either breast cancer mortality and/or breast cancer recurrence. The potential influence of competing risks was estimated using a validated multivariate linear model that predicts the amount that the KM risk estimates are biased relative to outcome risk measured with the cumulative incidence function (CIF). Results: The initial search identified 14 analyses published by the EBCTCG with 10 of the 14 studies (71%) susceptible to competing risk bias cited both the number of events of interest and competing events. Eight of the ten studies (80%) had a relative difference between the KM estimate and the competing risk adjusted estimate of more than 10% while 2 of 10 (20%) had a difference of less than 10%. The relative difference between the KM and adjusted estimates was 28.4% for local recurrence, 16.8% for distant recurrence, and 6.7% for breast cancer-specific mortality. There was 2.2% difference between KM and adjusted analyses between 0-4 years and 18.9% beyond 10 years of follow up. Use of KM and CIF-based analysis did not influence treatment effect in the majority of included studies. Conclusions: This study provides estimates for the overestimation of risk in Kaplan-Meier analyses resulting from failure to address competing risk bias. CIFs are more appropriate to measure outcome risk over time and should be used especially for long-term follow-up studies and for analysis of rare events.


Author(s):  
Mohammad Shoaib Abrahimi ◽  
Mark Elwood ◽  
Ross Lawrenson ◽  
Ian Campbell ◽  
Sandar Tin Tin

This study aimed to investigate type of loco-regional treatment received, associated treatment factors and mortality outcomes in New Zealand women with early-stage breast cancer who were eligible for breast conserving surgery (BCS). This is a retrospective analysis of prospectively collected data from the Auckland and Waikato Breast Cancer Registers and involves 6972 women who were diagnosed with early-stage primary breast cancer (I-IIIa) between 1 January 2000 and 31 July 2015, were eligible for BCS and had received one of four loco-regional treatments: breast conserving surgery (BCS), BCS followed by radiotherapy (BCS + RT), mastectomy (MTX) or MTX followed by radiotherapy (MTX + RT), as their primary cancer treatment. About 66.1% of women received BCS + RT, 8.4% received BCS only, 21.6% received MTX alone and 3.9% received MTX + RT. Logistic regression analysis was used to identify demographic and clinical factors associated with the receipt of the BCS + RT (standard treatment). Differences in the uptake of BCS + RT were present across patient demographic and clinical factors. BCS + RT was less likely amongst patients who were older (75+ years old), were of Asian ethnicity, resided in impoverished areas or areas within the Auckland region and were treated in a public healthcare facility. Additionally, BCS + RT was less likely among patients diagnosed symptomatically, diagnosed during 2000–2004, had an unknown tumour grade, negative/unknown oestrogen and progesterone receptor status or tumour sizes ≥ 20 mm, ≤50 mm and had nodal involvement. Competing risk regression analysis was undertaken to estimate the breast cancer-specific mortality associated with each of the four loco-regional treatments received. Over a median follow-up of 8.8 years, women who received MTX alone had a higher risk of breast cancer-specific mortality (adjusted hazard ratio: 1.38, 95% confidence interval (CI): 1.05–1.82) compared to women who received BCS + RT. MTX + RT and BCS alone did not have any statistically different risk of mortality when compared to BCS + RT. Further inquiry is needed as to any advantages BCS + RT may have over MTX alternatives.


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