title: Tumoral load quantification of positive sentinel lymph nodes in breast cancer to predict more than two involved nodes.
abstract: OBJECTIVE
  One-Step Nucleic Acid Amplification (OSNA) can detect isolated tumour loads in axillary lymph nodes of breast cancer patients. We investigated the predictability of the non-sentinel lymph node (SLN) metastatic involvement (MI) based on the OSNA SLN assessment in surgical invasive breast cancer.
  
  
  METHODS
  We studied surgical breast invasive carcinoma patients, not taking neoadjuvant chemotherapy, having SLN positive by OSNA and having received axillary lymphadenectomy. Age, basic histopathological, immunohistochemical, SLN biopsy and lymphadenectomy data were compared between patients with or without MI of more than 2 non-SLN in both univariate and multivariate analyses. The discriminating capacity of the multivariate model was characterized by the ROC AUC.
  
  
  RESULTS
  726 patients from 23 centers in Spain aged 55.3 ± 12.2 years were analysed. The univariate analysis comparing patients with or without MI of more than 2 non-SLN detected statistically significant differences in primary tumour size, multifocality, presence of lymphovascular infiltration, positive proliferation index with ki67, immunophenotype and logTTL (Tumour Total Load). The multivariate logistic analyses (OR (95% CI)) confirmed multifocality (2.16 (1.13-4.13), p = 0.019), lymphovascular infiltration (4.36 (2.43-7.82), p < 0.001) and logTTL (1.22 (1.10-1.35), p < 0.001) as independent predictors, and exhibit an AUC (95% CI) of 0.78 (0.72-0.83) with an overall fit (Hosmer-Lemeshow test) of 0.359. A change in the slope of both sensitivity and specificity is observed at about 10,000 copies/μL, without relevant changes in the Negative Predictive Values.
  
  
  CONCLUSIONS
  Using OSNA technique, the MI of more than 2 non-SLN can be reliably predicted.
authors.affiliation: Department of Surgery, "Virgen de la Arrixaca" University Hospital, 30120 Murcia, Spain. Electronic address: pineromadrona@gmail.com.
authors.forename: Antonio
authors.initials: A
authors.lastname: Piñero-Madrona
authors.affiliation: Department of Statistics, FFIS-IMIB, Luis Fontes Pagán, 9, 1ª Planta, 30120 Murcia, Spain. Electronic address: guadalupe.ruiz@carm.es.
authors.forename: Guadalupe
authors.initials: G
authors.lastname: Ruiz-Merino
authors.affiliation: Department of Pathology, Hospital of Xátiva, Crtra de Xàtiva a Silla, Km 1, Valencia, Spain. Electronic address: bernet_lai@gva.es.
authors.forename: Laia
authors.initials: L
authors.lastname: Bernet
authors.affiliation: Department of Nuclear Medicine, University Hospital, Hijos de Santiago Rodriguez, 16, 09002 Burgos, Spain. Electronic address: bmiguel@cyl.com.
authors.forename: Begoña
authors.initials: B
authors.lastname: Miguel-Martínez
authors.affiliation: Department of Surgery, Complejo Hospitalario de Navarra, La Arboleda, 4, Cizur Menor, 31190 Pamplona, Spain. Electronic address: fvicente@unav.es.
authors.forename: Francisco
authors.initials: F
authors.lastname: Vicente-García
authors.affiliation: Department of Pathology, University Hospital Txagorritxu, Jose Atxotegui s/n, 01009 Vitoria, Spain. Electronic address: mariaamparo.viguridiaz@osakidetza.net.
authors.forename: María A
authors.initials: MA
authors.lastname: Viguri-Díaz
authors.affiliation: Department of Surgery, Fundación Instituto Valenciano de Oncología, Prof. Beltrán Báguena, 8, 46009 Valencia, Spain. Electronic address: julia.gimenezcliment@gmail.com.
authors.forename: Julia
authors.initials: J
authors.lastname: Giménez-Climent
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology*; D018270:Carcinoma, Ductal, Breast / Q000235:genetics / Q000473:pathology*; D018275:Carcinoma, Lobular / Q000235:genetics / Q000473:pathology*; D005260:Female; D006801:Humans; D053539:Keratin-19 / Q000235:genetics*; D016015:Logistic Models; D008197:Lymph Node Excision; D008198:Lymph Nodes / Q000473:pathology*; D008875:Middle Aged; D015999:Multivariate Analysis; D009378:Neoplasms, Multiple Primary / Q000473:pathology*; D021141:Nucleic Acid Amplification Techniques; D012333:RNA, Messenger / Q000378:metabolism*; D018570:Risk Assessment; D021701:Sentinel Lymph Node Biopsy; D047368:Tumor Burden
chemical_list: D053539:Keratin-19; D012333:RNA, Messenger
keywords: Breast neoplasms; Intraoperative procedures; Keratin 19; One-step nucleic acid amplification assay; Sentinel lymph-node biopsy; mRNA copy number