Originally published as JCO Early Release 10.1200/JCO.2005.04.1665 on April 10 2006

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Sequential Preoperative or Postoperative Docetaxel Added to Preoperative Doxorubicin Plus Cyclophosphamide for Operable Breast Cancer: National Surgical Adjuvant Breast and Bowel Project Protocol B-27

Harry D. Bear, Stewart Anderson, Roy E. Smith, Charles E. Geyer, Jr, Eleftherios P. Mamounas, Bernard Fisher, Ann M. Brown, Andre Robidoux, Richard Margolese, Morton S. Kahlenberg, Soonmyung Paik, Atilla Soran, D. Lawrence Wickerham, Norman Wolmark

From the National Surgical Adjuvant Breast and Bowel Project; Department of Biostatistics, Graduate School of Public Health, and Department of Surgery, University of Pittsburgh; Allegheny General Hospital, Pittsburgh; Regional Cancer Center, Erie, PA; Virginia Commonwealth University, Medical College of Virginia School of Medicine and the Massey Cancer Center, Richmond, VA; Aultman Hospital Cancer Center, Canton, OH; University of Texas Health Science Center, San Antonio, TX; Hotel Dieu De Montréal Hospital; and Jewish General Hospital, McGill University, Montréal, Québec, Canada.

Address reprint requests to Harry D. Bear, MD, PhD, Box 980011, Division of Surgical Oncology, Virginia Commonwealth University Health System, Richmond, VA 23298-0011; e-mail: hdbear{at}vcu.edu

PURPOSE: This study was designed to determine the effect of adding docetaxel (T) to preoperative doxorubicin and cyclophosphamide (AC) on breast cancer response rates and disease-free survival (DFS) and overall survival (OS).

PATIENTS AND METHODS: Women with operable breast cancer (N = 2,411) were randomly assigned to receive preoperative AC followed by surgery, AC followed by T and surgery, or AC followed by surgery and then T. Tamoxifen was initiated concurrently with chemotherapy. Median time on study for 2,404 patients with follow-up was 77.9 months.

RESULTS: Addition of T to AC did not significantly impact DFS or OS. There were trends toward improved DFS with addition of T. The addition of T reduced the incidence of local recurrences as first events (P = .0034). Preoperative T, but not postoperative T, significantly improved DFS in patients who had a clinical partial response after AC (hazard ratio [HR] = 0.71; 95% CI, 0.55 to 0.91; P = .007). Pathologic complete response, which was doubled by addition of preoperative T, was a significant predictor of OS regardless of treatment (HR = 0.33; 95% CI, 0.23 to 0.47; P < .0001). Pathologic nodal status after chemotherapy was a significant predictor of OS (P < .0001).

CONCLUSION: The addition of preoperative or postoperative T after preoperative AC did not significantly affect OS, slightly improved DFS, and decreased the incidence of local recurrences. The sample size of this study was not sufficient to yield significance for the moderate DFS improvement. Concurrent use of tamoxifen may have limited the impact of adding T.

Supported by Public Health Service Grants No. U10-CA-37377, U10-CA-69974, U10-CA12027, and U10-CA-69651 from the National Cancer Institute, National Institutes of Health, Department of Health and Human Services.

Presented in part at the 27th Annual San Antonio Breast Cancer Symposium, San Antonio, TX, December 10-14, 2004. Also presented in part at the 24th Annual San Antonio Breast Cancer Symposium, San Antonio, TX, December 10-13, 2001.

H.D.B. is the study chair for this study and N.W. is the principal investigator of the National Surgical Adjuvant Breast and Bowel Project.

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

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