Novel intraoperative molecular test for sentinel lymph node metastases in patients with early-stage breast cancer

J Clin Oncol. 2008 Jul 10;26(20):3338-45. doi: 10.1200/JCO.2007.14.0665.

Abstract

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.

Publication types

  • Comparative Study
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / mortality
  • Adenocarcinoma / secondary*
  • Adenocarcinoma / surgery
  • Adult
  • Aged
  • Aged, 80 and over
  • Bayes Theorem
  • Biomarkers, Tumor / genetics
  • Breast Neoplasms / genetics
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology*
  • Breast Neoplasms / surgery
  • Breast Neoplasms, Male / genetics
  • Breast Neoplasms, Male / mortality
  • Breast Neoplasms, Male / pathology
  • Breast Neoplasms, Male / surgery
  • Female
  • Follow-Up Studies
  • Frozen Sections
  • Humans
  • Immunohistochemistry
  • Intraoperative Care / methods*
  • Lymphatic Metastasis
  • Male
  • Mastectomy / methods
  • Middle Aged
  • Neoplasm Staging
  • Prospective Studies
  • Reverse Transcriptase Polymerase Chain Reaction
  • Risk Assessment
  • Sentinel Lymph Node Biopsy*
  • Survival Analysis
  • Treatment Outcome

Substances

  • Biomarkers, Tumor