Abstract
Purpose
Several pathologic staging systems characterize residual tumor in patients undergoing neoadjuvant chemotherapy for breast cancer. Pathologic complete response (pCR) is now accepted by the Food and Drug Administration as an endpoint for granting accelerated drug approval. Two other systems of post-neoadjuvant pathologic tumor staging—residual cancer burden (RCB) and the American Joint Committee on Cancer post-neoadjuvant therapy staging system (yAJCC)—have been developed to characterize residual tumors when patients do not achieve pCR. The optimal system and the ways in which these systems complement each other have not been fully determined.
Methods
Using data from the I-SPY 1 TRIAL, we compared pCR, RCB, and yAJCC as predictors of early recurrence-free survival (RFS) to identify ways to improve post-neoadjuvant pathologic evaluation.
Results
Among 162 patients assessed, pCR identified patients at lowest risk of recurrence, while RCB and yAJCC identified patients at highest risk. Hormone-receptor (HR) and HER2 subtypes further improved risk prediction. Recursive partitioning indicated that triple-negative or HER2+ patients with yAJCC III or RCB 3 have the highest recurrence risk, with an RFS of 27%. Our analysis also highlighted discrepancies between RCB and yAJCC stratification: 31% of patients had discrepant RCB and yAJCC scores. We identified differential treatment of lymph node involvement and tumor cellularity as drivers of these discrepancies.
Conclusions
These data indicate that there is benefit to reporting both RCB and yAJCC for patients in order to identify those at highest risk of relapse.
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Acknowledgements
The authors would like to thank the patients in the I-SPY 1 TRIAL, as well as the study staff who support it. We would also like to thank the I-SPY Data & Publications Committee and the CALGB Review committee for their reviews and comments on this manuscript.
Funding sources
National Cancer Institute Specialized Program of Research Excellence in Breast Cancer (CA58207), American College of Radiology Imaging Network (CA079778 and CA080098), Cancer and Leukemia Group B (CA31964 and CA33601), National Cancer Institute Center for Bioinformatics, The Breast Cancer Research Foundation, Bruce and Martha Atwater, and ‘‘Give Breast Cancer the Boot.” Additional funding came from grants from the National Cancer Institute (CA31946) to the Alliance for Clinical Trials in Oncology (Monica M. Bertagnolli, M.D., Chair) and to the Alliance Statistics and Data Center (Daniel J. Sargent, Ph.D., CA33601). The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute. The following institutions participated in this study: (1) Georgetown University Medical Center, Washington, DC, Bruce Cheson, M.D., supported by CA77597. (2) Memorial Sloan-Kettering Cancer Center, New York, NY, Clifford A. Hudis, M.D., supported by CA77651. (3) University of Alabama, Birmingham, AL (ECOG). (4) University of California at San Francisco, San Francisco, CA, Charles J. Ryan, M.D., supported by CA60138. (5) University of Chicago, Chicago, IL, Hedy L. Kindler, M.D., supported by CA41287. (6) University of Minnesota, Minneapolis, MN, Bruce A. Peterson, M.D., supported by CA16450. (7) University of North Carolina at Chapel Hill, Chapel Hill, NC, Thomas C. Shea, M.D., supported by CA47559. (8) University of Pennsylvania, Philadelphia, PA (ECOG). (9) University of Texas Southwestern Medical Center, Dallas, TX, supported by CA37347. (10) University of Washington, Seattle WA (SWOG).
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Affiliation at the time the authors (David Chhieng and Chad Livasy) did the work.
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Campbell, J.I., Yau, C., Krass, P. et al. Comparison of residual cancer burden, American Joint Committee on Cancer staging and pathologic complete response in breast cancer after neoadjuvant chemotherapy: results from the I-SPY 1 TRIAL (CALGB 150007/150012; ACRIN 6657). Breast Cancer Res Treat 165, 181–191 (2017). https://doi.org/10.1007/s10549-017-4303-8
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DOI: https://doi.org/10.1007/s10549-017-4303-8