Originally published as JCO Early Release 10.1200/JCO.2007.10.6823 on September 4 2007

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Measurement of Residual Breast Cancer Burden to Predict Survival After Neoadjuvant Chemotherapy

W. Fraser Symmans, Florentia Peintinger, Christos Hatzis, Radhika Rajan, Henry Kuerer, Vicente Valero, Lina Assad, Anna Poniecka, Bryan Hennessy, Marjorie Green, Aman U. Buzdar, S. Eva Singletary, Gabriel N. Hortobagyi, Lajos Pusztai

From the Departments of Pathology, Surgery, and Breast Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston, TX; and Nuvera Biosciences Inc, Woburn, MA

Address reprint requests to W. Fraser Symmans, MD, Department of Pathology, Unit 85, The University of Texas M.D. Anderson Cancer Center,1515 Holcombe Blvd, Houston, TX 77030-4009; e-mail: fsymmans{at}mdanderson.org

Purpose To measure residual disease after neoadjuvant chemotherapy in order to improve the prognostic information that can be obtained from evaluating pathologic response.

Patients and Methods Pathologic slides and reports were reviewed from 382 patients in two different treatment cohorts: sequential paclitaxel (T) then fluorouracil, doxorubicin, and cyclophosphamide (FAC) in 241 patients; and a single regimen of FAC in 141 patients. Residual cancer burden (RCB) was calculated as a continuous index combining pathologic measurements of primary tumor (size and cellularity) and nodal metastases (number and size) for prediction of distant relapse-free survival (DRFS) in multivariate Cox regression analyses.

Results RCB was independently prognostic in a multivariate model that included age, pretreatment clinical stage, hormone receptor status, hormone therapy, and pathologic response (pathologic complete response [pCR] v residual disease [RD]; hazard ratio = 2.50; 95% CI 1.70 to 3.69; P < .001). Minimal RD (RCB-I) in 17% of patients carried the same prognosis as pCR (RCB-0). Extensive RD (RCB-III) in 13% of patients was associated with poor prognosis, regardless of hormone receptor status, adjuvant hormone therapy, or pathologic American Joint Committee on Cancer stage of residual disease. The generalizability of RCB for prognosis of distant relapse was confirmed in the FAC-treated validation cohort.

Conclusion RCB determined from routine pathologic materials represented the distribution of RD, was a significant predictor of DRFS, and can be used to define categories of near-complete response and chemotherapy resistance.

Published online ahead of print at www.jco.org on September 4, 2007.

Supported by a research Grant No. DAMD17-02-1-0458 01 from Department of Defense Breast Cancer Research Program (W.F.S.) and the Nellie B. Connally Breast Cancer Research Fund.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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