title: Intraoperative molecular analysis of total tumor load in sentinel lymph node: a new predictor of axillary status in early breast cancer patients.
abstract: OBJECTIVE
  To assess the intraoperative positive sentinel lymph node (SLN) total tumor load (TTL, defined as the amount of CK19 mRNA copies [copies/μL] in all positive SLNs) obtained by one-step nucleic acid amplification (OSNA) and to determine whether it is predictive of non-SLNs involvement. SUMMARY/BACKGROUND/DATA: The OSNA assay (Sysmex Corporation, Kobe, Japan) is a new diagnostic technique that uses molecular biological techniques to analyze SLN that has been validated as an accurate method for detection of positive SLN. Although the American College of Surgeons Oncology Group Z0011 trial has defined a select cohort of patients in whom a completion axillary lymph node dissection (cALND) may be safely omitted, there are a still a number of patients where prediction of non-SLN metastasis may be helpful for cALND decision making. Multiple studies suggest that specific pathologic characteristics of the primary tumor and the SLN metastases are associated with an increased likelihood of additional positive non-SLN.
  
  
  METHODS
  This is a retrospective multicentric cohort study of 697 patients with cT1-3N0 breast cancer, who had had intraoperative SLN evaluation by OSNA assay with a cALND. TTL is defined as the amount of CK19 mRNA copies number in all positives SLN (copies/μL).
  
  
  RESULTS
  Univariate logistic regression showed that, in addition to TTL (p < 0.001), the number of affected SLNs (p < 0.001), tumor size (p < 0.001), HER2 status (p = 0.007), and lymphovascular invasion (LVI, p < 0.001) were predictive of ALND status. The multivariate logistic regression analysis showed that TTL is an independent predictor of metastatic non-SLNs, after adjusting for the tumor size, HER2 status, LVI and, in particular, the number of affected SLNs.
  
  
  CONCLUSIONS
  TTL by OSNA is a newly standardized and automated tool that predicts axillary node status better and independently of the number of affected SLNs and the type of surgery. This value can then help clinicians to personalize surgical treatment. Prospective studies will be carried out to determine the clinical impact of this variable in the management of patients.
authors.affiliation: Department of Pathology, Vall d'Hebron University Hospital, Barcelona, Spain. vpeg@vhebron.net
authors.forename: Vicente
authors.initials: V
authors.lastname: Peg
authors.forename: Martín
authors.initials: M
authors.lastname: Espinosa-Bravo
authors.forename: Begoña
authors.initials: B
authors.lastname: Vieites
authors.forename: Felip
authors.initials: F
authors.lastname: Vilardell
authors.forename: José R
authors.initials: JR
authors.lastname: Antúnez
authors.forename: Magdalena Sancho
authors.initials: MS
authors.lastname: de Salas
authors.forename: Julio J
authors.initials: JJ
authors.lastname: Delgado-Sánchez
authors.forename: Willy
authors.initials: W
authors.lastname: Pinto
authors.forename: Francisco
authors.initials: F
authors.lastname: Gozalbo
authors.forename: Anna
authors.initials: A
authors.lastname: Petit
authors.forename: Irene
authors.initials: I
authors.lastname: Sansano
authors.forename: María
authors.initials: M
authors.lastname: Del Mar Téllez
authors.forename: Isabel T
authors.initials: IT
authors.lastname: Rubio
mesh_terms: D000368:Aged; D019540:Area Under Curve; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007432:Intraoperative Period; D053539:Keratin-19 / Q000032:analysis* / Q000235:genetics; D008207:Lymphatic Metastasis / Q000175:diagnosis*; D008875:Middle Aged; D021141:Nucleic Acid Amplification Techniques / Q000379:methods*; D012333:RNA, Messenger / Q000032:analysis; D012372:ROC Curve; D012189:Retrospective Studies; D021701:Sentinel Lymph Node Biopsy; D047368:Tumor Burden
chemical_list: D053539:Keratin-19; D012333:RNA, Messenger