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Validation of the AJCC 8th Edition Breast Cancer Prognostic Staging System in Legacy Alliance Trials (AFT-01)

  • Breast Oncology
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

The 8th edition American Joint Committee on Cancer staging system combined anatomic stage (AS) with receptor status and grade to create prognostic stage (PS). PS has been validated in single-institution and cancer registry studies; however, missing human epidermal growth factor receptor 2 (HER2) status and variable treatment and follow-up create limitations.

Objective

Our objective was to compare the relative prognostic ability of PS versus AS to predict survival using breast cancer clinical trial data.

Methods

Women with non-metastatic breast cancer enrolled in six Alliance for Clinical Trials in Oncology trials were included (enrollment years 1997–2010). AS and PS were constructed using pathological tumor size, nodal status, estrogen receptor (ER), progesterone receptor (PR), HER2 status, and grade. Unadjusted Cox proportional hazard models were estimated to predict overall survival within 5 years, with AS and PS as predictor variables. The relative predictive power of staging models was assessed by comparing Harrell concordance indices (C-indices). Kaplan–Meier-based mortality estimates were compared by stage.

Results

Overall, 6924 women were included (median age 53 years); 45.2% were diagnosed with ER+/PR+/HER2− tumors, 26.2% with HER2+ tumors, and 17.1% with ER−/PR−/HER2− tumors. Median follow-up time was 5 years (interquartile range 2.95–5.00). PS significantly improved predictive performance (C-index 0.721) for overall survival compared with AS (0.700) (p = 0.020). Kaplan–Meier hazard estimates suggested PS did not distinguish mortality risk between patients with IIB and IIIA or IB and IIA disease.

Conclusions

PS has significantly improved predictive performance for OS compared with AS. As systemic therapies evolve, it will be important to re-evaluate the prognostic staging system, particularly for patients with intermediate-stage cancers.

ClinicalTrials.gov Identifier: NCT02171078

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Funding

This work was supported by the Patient Centered Outcomes Research Institute (PCORI) [CCG, JRS, HBN, AHP, SBE; CE-1304-6543]. This publication was further made possible by the National Cancer Institute at the National Institute of Health (NIH)-funded Alliance for Clinical Trials in Oncology (U10CA180821), Building Interdisciplinary Research Careers in Women’s Health Scholar Program (HBN; NIH K12 HD055894), and the National Cancer Institute-funded Surgical Oncology Research Training Program (LKK; T32 CA090217). The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of the PCORI, its Board of Governors or Methodology Committee, or the NIH (https://acknowledgments.alliancefound.org).

Author information

Authors and Affiliations

  1. Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA

    Laura K. Krecko MD, Heather B. Neuman MD, MS, Lee G. Wilke MD, Bret M. Hanlon PhD, Dou-Yan Yang PhD, Jeffrey Havlena MS & Jessica R. Schumacher PhD

  2. Department of Surgery, University of Wisconsin Carbone Cancer Center, Madison, WI, USA

    Heather B. Neuman MD, MS, Lee G. Wilke MD & Jessica R. Schumacher PhD

  3. Department of Surgery, University of North Carolina-Chapel Hill, Chapel Hill, NC, USA

    Caprice C. Greenberg MD, MPH & Jessica R. Schumacher PhD

  4. Department of Biostatistics and Medical Informatics, Madison, WI, USA

    Bret M. Hanlon PhD

  5. Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center and University at Buffalo, Buffalo, NY, USA

    Stephen B. Edge MD

  6. Department of Oncology, Mayo Clinic, Rochester, MN, USA

    Kathryn J. Ruddy MD, MPH

  7. Department of Medical Oncology, Dana Farber/Partners CancerCare, Boston, MA, USA

    Ann H. Partridge MD, MPH

  8. Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA

    Jennifer Le-Rademacher PhD

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  1. Laura K. Krecko MD
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Corresponding author

Correspondence to Jessica R. Schumacher PhD.

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Disclosure

Lee G. Wilke is a minority stock owner and founder of Elucent Medical. Laura K. Krecko, Heather B. Neuman, Caprice C. Greenberg, Bret M. Hanlon, Stephen B. Edge, Kathryn J. Ruddy, Ann H. Partridge, Jennifer Le-Rademacher, Dou-Yan Yang, Jeffrey Havlena, and Jessica R. Schumacher have no conflicts of interest to declare.

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Krecko, L.K., Neuman, H.B., Greenberg, C.C. et al. Validation of the AJCC 8th Edition Breast Cancer Prognostic Staging System in Legacy Alliance Trials (AFT-01). Ann Surg Oncol (2024). https://doi.org/10.1245/s10434-024-15477-5

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