Prediction of metastatic breast cancer in non-sentinel lymph nodes based on metalloprotease-1 expression by the sentinel lymph node.
OBJECTIVE
Sentinel lymph node (SLN) biopsy is the current standard axillary approach for patients with clinically node-negative breast cancer. If the SLN is positive, is still also standard in most centres to proceed with a complete axillary dissection to predict the remaining nodes affectation, despite of SLN is the only positive lymph node in 50-68% of cases. If we could identify them, these patients could be spared a complete axillary dissection.


METHODS
Elevated expression of specific matrix metalloproteases (MMPs) and their inhibitors (TIMPs) by stromal mononuclear inflammatory cells (MICs) of primary tumours is significantly associated with distant metastasis development in breast cancer. In the present study we first identified candidate MMPs/TIMPs associated with axillary metastasis in a preliminary group (n=50), and subsequently examined the potential of their expression in the SLN for predicting the status of the remaining nodes, in 105 patients with intraoperative SLN-assessment.


RESULTS
MMP-1 expression by MICs from SLNs was significantly associated with metastatic spread to non-SLNs. Moreover, in all cases with negative MMP-1 expression by MICs from SLNs, the remaining non-SLNs were not affected (p<0.0001). Therefore, we demonstrate that MMP-1 expression by MICs from SLNs had 100% sensitivity, 100% negative-predictive value and 61.5% specificity to predict non-SLNs status.


CONCLUSIONS
This is the first time that tumour spread to the remaining axillary nodes has been predicted from molecular features of the SLN(s). If confirmed in larger studies, patients could be spared the morbidity associated with an unnecessary complete lymphadenectomy.
Unidad de Investigación, Fundación Hospital de Jove, Gijón, Spain.
Noemí
N
Eiró
Luis O
LO
González
Sara
S
Atienza
José M
JM
González-Quintana
Nana
N
Beridze
Belen
B
Fernandez-Garcia
Román
R
Pérez-Fernández
Tomás
T
García-Caballero
José
J
Schneider
Francisco J
FJ
Vizoso
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008198:Lymph Nodes / Q000378:metabolism* / Q000473:pathology; D008207:Lymphatic Metastasis; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism*; D020782:Matrix Metalloproteinases / Q000378:metabolism; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D012680:Sensitivity and Specificity; D021701:Sentinel Lymph Node Biopsy; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism
D019714:Tissue Inhibitor of Metalloproteinases; D020782:Matrix Metalloproteinases; D020781:Matrix Metalloproteinase 1