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Nomograms to Predict Pathologic Complete Response and Metastasis-Free Survival After Preoperative Chemotherapy for Breast Cancer

From the Departments of Breast Medical Oncology, Biostatistics and Applied Mathematics, and Pathology, The University of Texas M.D. Anderson Cancer Center, Houston, TX; Breast Cancer Unit and UPRES EA, Institut Gustave Roussy, Villejuif, France; and Departments of Gynecologic Oncology and Breast Cancer Surgery (DA), Hotel-Dieu, Beirut, Lebanon.

Address reprint requests to Lajos Pusztai, MD, DPhil, Department of Breast Medical Oncology, Unit 1354, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77230-1439; e-mail: lpusztai{at}mdanderson.org

PURPOSE: To combine clinical variables associated with pathologic complete response (pCR) and distant metastasis–free survival (DMFS) after preoperative chemotherapy (PC) into a prediction nomogram.

PATIENTS AND METHODS: Data from 496 patients treated with anthracycline PC at the Institut Gustave Roussy were used to develop and calibrate a nomogram for pCR based on multivariate logistic regression. This nomogram was tested on two independent cohorts of patients treated at the M.D. Anderson Cancer Center. The first cohort (n = 337) received anthracycline; the second cohort (n = 237) received a combination of paclitaxel and anthracycline PC. A separate nomogram to predict DMFS was developed using Cox proportional hazards regression model.

RESULTS: The pCR nomogram based on clinical stage, estrogen receptor status, histologic grade, and number of preoperative chemotherapy cycles had good discrimination and calibration in the training and the anthracycline-treated validation sets (concordance indices, 0.77, 0.79). In the paclitaxel plus anthracycline group, when the predicted pCR rate was less than 14%, the observed rate was 7.5%; for a predicted rate of 38%, the actual rate was 85%. For a predicted rate between 14% to 38%, the observed rates were 50% with weekly and 27% with 3-weekly paclitaxel. This indicates that patients with intermediate chemotherapy sensitivity benefit the most from the optimized schedule of paclitaxel. Patients unlikely to achieve pCR to anthracylines remain at low probability for pCR, even after inclusion of paclitaxel. The nomogram for DMFS had a concordance index of 0.72 in the validation set and outperformed other prediction tools (P = .02).

CONCLUSION: Our nomograms predict pCR accurately and can serve as a basis to integrate future molecular markers into a clinical prediction model.

Supported by the Nellie B. Connally Breast Cancer Research Fund. R.R. was supported in part by a grant from Philippe Foundation, Paris and New York. L.P. is supported by RO1 CA106290-01 of the National Cancer Institute.

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

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