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Preoperative Chemotherapy: Updates of National Surgical Adjuvant Breast and Bowel Project Protocols B-18 and B-27

Priya Rastogi, Stewart J. Anderson, Harry D. Bear, Charles E. Geyer, Morton S. Kahlenberg, André Robidoux, Richard G. Margolese, James L. Hoehn, Victor G. Vogel, Shaker R. Dakhil, Deimante Tamkus, Karen M. King, Eduardo R. Pajon, Mary Johanna Wright, Jean Robert, Soonmyung Paik, Eleftherios P. Mamounas, Norman Wolmark

From the National Surgical Adjuvant Breast and Bowel Project Operations Office and Biostatistical Center; University of Pittsburgh Cancer Institute/Magee Womens Hospital; Department of Biostatistics, University of Pittsburgh, Graduate School of Public Health; Allegheny General Hospital, Pittsburgh, PA; Virginia Commonwealth University School of Medicine and the Massey Cancer Center, Richmond, VA; University of Texas Health Science Center at San Antonio, San Antonio, TX; Community Clinical Oncology Program Marshfield Clinic, Marshfield, WI; Cancer Center of Kansas, Wichita, KS; Division of Hematology/Oncology, Department of Medicine, Michigan State University College of Human Medicine, East Lansing, MI; Colorado Cancer Research Program, Denver, CO; Tulane University Health Sciences Center, New Orleans, LA; Cancer Center, Aultman Hospital Health Foundation, and Department of Surgery, Northeastern Ohio Universities College of Medicine, Canton, OH; Centre Hospitalier de l'Université de Montréal; Jewish General Hospital, McGill University, Montréal, Centre Hospitalier Affilié Universitaire de Québec (CHA)-Hôpital du Saint-Sacrement, Québec, Québec; Cross Cancer Institute, Edmonton, Alberta, Canada

Corresponding author: Priya Rastogi, MD, University of Pittsburgh Cancer Institute/Magee Womens Hospital, 300 Halket St, Room 3524, Pittsburgh, PA 15213; e-mail: rastogip{at}upmc.edu

Purpose National Surgical Adjuvant Breast and Bowel Project (NSABP) Protocol B-18 was designed to determine whether four cycles of doxorubicin and cyclophosphamide (AC) administered preoperatively improved breast cancer disease-free survival (DFS) and overall survival (OS) compared with AC administered postoperatively. Protocol B-27 was designed to determine the effect of adding docetaxel (T) to preoperative AC on tumor response rates, DFS, and OS.

Patients and Methods Analyses were limited to eligible patients. In B-18, 751 patients were assigned to receive preoperative AC, and 742 patients were assigned to receive postoperative AC. In B-27, 784 patients were assigned to receive preoperative AC followed by surgery, 783 patients were assigned to AC followed by T and surgery, and 777 patients were assigned to AC followed by surgery and then T.

Results Results from B-18 show no statistically significant differences in DFS and OS between the two groups. However, there were trends in favor of preoperative chemotherapy for DFS and OS in women less than 50 years old (hazard ratio [HR] = 0.85, P = .09 for DFS; HR = 0.81, P = .06 for OS). DFS conditional on being event free for 5 years also demonstrated a strong trend in favor of the preoperative group (HR = 0.81, P = .053). Protocol B-27 results demonstrated that the addition of T to AC did not significantly impact DFS or OS. Preoperative T added to AC significantly increased the proportion of patients having pathologic complete responses (pCRs) compared with preoperative AC alone (26% v 13%, respectively; P < .0001). In both studies, patients who achieved a pCR continue to have significantly superior DFS and OS outcomes compared with patients who did not.

Conclusion B-18 and B-27 demonstrate that preoperative therapy is equivalent to adjuvant therapy. B-27 also showed that the addition of preoperative taxanes to AC improves response.

Supported in part by Public Health Service Grants No. U10CA-12027, U10CA-69974, U10CA-37377, and U10CA-69651 from the National Cancer Institute, Department of Health and Human Services, and by AstraZeneca and sanofi-aventis.

Presented in part at the Preoperative Therapy in Invasive Breast Cancer: Reviewing the State of the Science and Exploring New Research Directions, meeting hosted by the National Cancer Institute, March 26-27, 2007, Bethesda, MD.

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

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