J Cancer 2023; 14(2):193-199. doi:10.7150/jca.79797 This issue Cite

Research Paper

Effectiveness Without Efficacy: Cautionary Tale from a Landmark Breast Cancer Randomized Controlled Trial

Yu Shen1✉, Jing Ning1, Heather Y Lin1, Simona F. Shaitelman2, Henry M Kuerer3, Isabelle Bedrosian3

1. Department of Biostatistics, The University of Texas, MD Anderson Cancer Center, Houston TX, USA.
2. Department of Radiation Oncology, The University of Texas, MD Anderson Cancer Center, Houston TX, USA.
3. Department of Breast Surgical Oncology, The University of Texas, MD Anderson Cancer Center, Houston TX, USA.

Citation:
Shen Y, Ning J, Lin HY, Shaitelman SF, Kuerer HM, Bedrosian I. Effectiveness Without Efficacy: Cautionary Tale from a Landmark Breast Cancer Randomized Controlled Trial. J Cancer 2023; 14(2):193-199. doi:10.7150/jca.79797. https://www.jcancer.org/v14p0193.htm
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Abstract

Graphic abstract

Background: “Old” randomized controlled trials established breast conserving therapy (BCT) and total mastectomy (TM) equivalence for treating early breast cancer, whereas recent literature report improved survival with BCT. To reconcile this, we performed a simulation study and re-analyzed B-06 trial data.

Methods: We estimated the distributions for overall survival (OS), cumulative incidence functions for breast-cancer-specific death (BCSD) and other causes-specific death (OCSD) by BCT and TM. The restricted mean survival time (RMST) difference and hazard ratio between the two arms were estimated. Given the estimated distributions, we simulated cause-specific death times from each arm, evaluating the power to test treatment difference in OS, BCSD, and OCSD with different sample sizes, follow-up times, and a modified setting by simulating BCT-arm OCSD times from the distribution of patients not receiving radiation.

Results: With 200 months follow-up, the average BCT-over-TM gain measured by RMST was 3.7 months for OS and 4.5 months for BCSD. Increasing the trial size to 5,000 per arm, there is a 79.2% chance to detect the OS benefit with RMST and 92.4% for BCSD. A nonproportional increase of OCSD in BCT compared to TM was observed after 144 months, and particularly after 200 months post treatments. When OCSD times of BCT were simulated using patients not receiving radiation, the estimated OS gain increased to 4.4 months, and the power increased to 92.2%.

Conclusions: The late excess other-cause-death, likely due to radiation, in the BCT arm and sample size constraints limited the power to report BCT superiority. Given radiation delivered in the era of B-06 trial, BCT and TM remain largely equivalent.

Keywords: Breast conserving therapy, Competing risks analysis, Randomized clinical trial, Total mastectomy


Citation styles

APA
Shen, Y., Ning, J., Lin, H.Y., Shaitelman, S.F., Kuerer, H.M., Bedrosian, I. (2023). Effectiveness Without Efficacy: Cautionary Tale from a Landmark Breast Cancer Randomized Controlled Trial. Journal of Cancer, 14(2), 193-199. https://doi.org/10.7150/jca.79797.

ACS
Shen, Y.; Ning, J.; Lin, H.Y.; Shaitelman, S.F.; Kuerer, H.M.; Bedrosian, I. Effectiveness Without Efficacy: Cautionary Tale from a Landmark Breast Cancer Randomized Controlled Trial. J. Cancer 2023, 14 (2), 193-199. DOI: 10.7150/jca.79797.

NLM
Shen Y, Ning J, Lin HY, Shaitelman SF, Kuerer HM, Bedrosian I. Effectiveness Without Efficacy: Cautionary Tale from a Landmark Breast Cancer Randomized Controlled Trial. J Cancer 2023; 14(2):193-199. doi:10.7150/jca.79797. https://www.jcancer.org/v14p0193.htm

CSE
Shen Y, Ning J, Lin HY, Shaitelman SF, Kuerer HM, Bedrosian I. 2023. Effectiveness Without Efficacy: Cautionary Tale from a Landmark Breast Cancer Randomized Controlled Trial. J Cancer. 14(2):193-199.

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
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