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Preoperative Therapy in Invasive Breast Cancer: Pathologic Assessment and Systemic Therapy Issues in Operable Disease

Julie R. Gralow, Harold J. Burstein, William Wood, Gabriel N. Hortobagyi, Luca Gianni, Gunter von Minckwitz, Aman U. Buzdar, Ian E. Smith, William F. Symmans, Baljit Singh, Eric P. Winer

From the Department of Medicine/Oncology, University of Washington, and Fred Hutchinson Cancer Research Center, Seattle, WA; Department of Medicine, Dana-Farber Cancer Institute, Boston, MA; Department of Surgery, Emory University School of Medicine, Atlanta, GA; Departments of Breast Medical Oncology and Pathology, The University of Texas M.D. Anderson Cancer Center, Houston, TX; Department of Medical Oncology, Istituto Nazionale Tumori, Milan, Italy; German Breast Group, Neu-Isenburg/University Womens Hospital, Frankfurt, Germany; Breast Unit, Royal Marsden Hospital, London, United Kingdom; and Department of Pathology, New York University Medical Center, New York, NY

Corresponding author: Julie R. Gralow, MD, Seattle Cancer Care Alliance, Department of Medicine, 825 Eastlake Ave, EMS G3-200, Seattle, WA 98109-1023; e-mail: pink{at}u.washington.edu

Purpose To review the state of the science with respect to preoperative systemic therapy and pathologic assessment in operable breast cancer.

Methods This article reviews data presented at the National Cancer Institute State of the Science Conference on Preoperative Therapy in Invasive Breast Cancer as well as supporting published data.

Results Preoperative chemotherapy in operable breast cancer has been shown to improve breast conservation rates as a result of tumor response to therapy. When patients are given preoperative systemic therapy, regimens should be the same as those established as safe and active in the adjuvant setting. At present, there are no data to suggest that systemic treatment should be tailored based on initial tumor response, or based on the extent of residual disease. In operable breast cancer, there seems to be no survival advantage from initiation of systemic therapy before surgery. A variety of clinical, imaging, and pathologic measurements are available to gauge tumor response to treatment. There is a clear correlation between tumor response in the breast and lymph nodes and both disease-free and overall survival. Pathologic complete response and other pathologic measures may be useful as surrogate end points in evaluating and understanding new therapies.

Conclusion In operable breast cancer, preoperative systemic therapy is effective and can improve breast conservation rates. Unless the tumor is large or the patient is in a clinical trial, postoperative adjuvant systemic therapy is the standard of care. To achieve optimal outcomes, preoperative systemic therapy must be administered as part of a coordinated, multimodality treatment program. The preoperative setting provides a unique opportunity to study the impact of systemic therapies on breast cancer biology.

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

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