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


CONCLUSIONS
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.
Julian
Thomas B
TB
Allegheny Breast Care Center, Allegheny General Hospital, 320 E North Ave, Pittsburgh, PA 15212, USA. tjulian@wpahs.org
Blumencranz
Peter
P
Deck
Kenneth
K
Whitworth
Pat
P
Berry
Donald A
DA
Berry
Scott M
SM
Rosenberg
Anne
A
Chagpar
Anees B
AB
Reintgen
Douglas
D
Beitsch
Peter
P
Simmons
Rache
R
Saha
Sukamal
S
Mamounas
Eleftherios P
EP
Giuliano
Armando
A
D000230:Adenocarcinoma / Q000235:genetics / Q000401:mortality / Q000556:secondary* / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001499:Bayes Theorem; D014408:Biomarkers, Tumor / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D018567:Breast Neoplasms, Male / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000601:surgery; D005260:Female; D005500:Follow-Up Studies; D005629:Frozen Sections; D006801:Humans; D007150:Immunohistochemistry; D007430:Intraoperative Care / Q000379:methods*; D008207:Lymphatic Metastasis; D008297:Male; D008408:Mastectomy / Q000379:methods; D008875:Middle Aged; D009367:Neoplasm Staging; D011446:Prospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018570:Risk Assessment; D021701:Sentinel Lymph Node Biopsy; D016019:Survival Analysis; D016896:Treatment Outcome
D014408:Biomarkers, Tumor