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Novel Intraoperative Molecular Test for Sentinel Lymph Node Metastases in Patients With Early-Stage Breast Cancer

Thomas B. Julian, Peter Blumencranz, Kenneth Deck, Pat Whitworth, Donald A. Berry, Scott M. Berry, Anne Rosenberg, Anees B. Chagpar, Douglas Reintgen, Peter Beitsch, Rache Simmons, Sukamal Saha, Eleftherios P. Mamounas, Armando Giuliano

From the Department of Human Oncology, Allegheny General Hospital/Allegheny Cancer Center, Pittsburgh; Department of Surgery, Jefferson University Hospital, Philadelphia, PA; Department of Surgery, Morton Plant Mease Healthcare, Clearwater; Department of Surgery, Lakeland Regional Medical Center, Lakeland, FL; Department of Surgery, South Orange County Surgical Medical Group, Laguna Hills; Department of Surgery, John Wayne Cancer Institute, Santa Monica, CA; Nashville Breast Center, Nashville, TN; Berry Consultants LLC, Houston; Department of Surgery, Dallas Surgical Group, Dallas, TX; Department of Surgery, University of Louisville, Louisville, KY; Department of Surgery, Weill-Cornell Breast Center, New York, NY; Department of Surgery, McLaren Regional Medical Center, Flint, MI; and Department of Surgery, Aultman Hospital, Canton, OH

Corresponding author: Thomas B. Julian, MD, Allegheny Breast Care Center, Allegheny General Hospital, 320 E North Ave, Pittsburgh, PA 15212; e-mail: tjulian{at}wpahs.org

Purpose An accurate, intraoperative sentinel lymph node (SLN) test could decrease delayed axillary dissections. Molecular tests may be more sensitive than current intraoperative tests but historically have not been rapid enough and have not been properly validated. We present the results from a large, prospective evaluation of the first rapid molecular SLN test, the Breast Lymph Node (BLN) Assay.

Methods A beta trial (n = 304) to determine the threshold levels of mammaglobin and cytokeratin 19 correlating with metastasis greater than 0.2 mm and a validation trial (n = 416) to validate the threshold cutoffs were conducted. Alternating portions from each SLN were processed for histology and the BLN Assay.

Results BLN Assay performance against extensive permanent-section histology verified by central pathology review was similar to that expected of standard permanent-section histology: sensitivity, 87.6%; specificity, 94.2%; positive predictive value, 86.2%; and negative predictive value (NPV), 94.9%. In 319 patients with both frozen-section hematoxylin and eosin results and BLN Assay results, the BLN Assay had higher sensitivity (95.6%) and NPV (98.2%) than frozen section (sensitivity, 85.6%; NPV, 94.5%). The assay can be performed in approximately 36 to 46 minutes for one to three nodes.

Conclusion The BLN Assay allows a rapid evaluation of 50% of each SLN. Comparison with permanent-section histology on adjacent node pieces evaluated by expert pathologists indicated that the BLN Assay was more sensitive than current intraoperative techniques while maintaining high specificity. These data indicate that the assay may be clinically useful for intraoperative or postoperative axillary lymph node dissection decisions.

Supported by Veridex LLC.

Presented in part at the 12th Annual Meeting of the Association for Molecular Pathology, November 16-19, 2006, Orlando, FL; 8th Annual Meeting of the American Society of Breast Surgeons, May 2-6, 2007, Phoenix, AZ; 43rd Annual Meeting of the American Society of Clinical Oncology, June 1-5, 2007, Chicago, IL; American Society of Clinical Oncology Breast Cancer Symposium, September 7-8, 2007, San Francisco, CA; Annual Meeting of the College of American Pathology, September 9-13, 2006,San Diego, CA; 6th Biennial Meeting of International Sentinel Node Society, November 1-4, 2006, Rome, Italy; 29th Annual Meeting of the San Antonio Breast Cancer Symposium, December 14-17, 2006, San Antonio, TX; Annual Meeting of the Society of Surgical Oncology, March 15-18, 2007, Washington, DC; 30th Annual Meeting of the San Antonio Breast Cancer Symposium, December 13-16, 2007, San Antonio, TX.

Terms in blue are defined in the glossary, found at the end of this article and online at www.jco.org.

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

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