title: International multicenter tool to predict the risk of nonsentinel node metastases in breast cancer.
abstract: BACKGROUND
  Axillary treatment of breast cancer patients is undergoing a paradigm shift, as completion axillary lymph node dissections (ALNDs) are being questioned in the treatment of patients with tumor-positive sentinel nodes. This study aims to develop a novel multi-institutional predictive tool to calculate patient-specific risk of residual axillary disease after tumor-positive sentinel node biopsy.
  
  
  METHODS
  Breast cancer patients with a tumor-positive sentinel node and a completion ALND from five European centers formed the original patient series (N = 1000). Statistically significant variables predicting nonsentinel node involvement were identified in logistic regression analysis. A multivariable predictive model was developed and validated by area under the receiver operating characteristics curve (AUC), first internally in 500 additional patients and then externally in 1068 patients from other centers. All statistical tests were two-sided.
  
  
  RESULTS
  Nine tumor- and sentinel node-specific variables were identified as statistically significant factors predicting nonsentinel node involvement in logistic regression analysis. A resulting predictive model applied to the internal validation series resulted in an AUC of 0.714 (95% confidence interval [CI] = 0.665 to 0.763). For the external validation series, the AUC was 0.719 (95% CI = 0.689 to 0.750). The model was well calibrated in the external validation series.
  
  
  CONCLUSIONS
  We present a novel, international, multicenter, predictive tool to assess the risk of additional axillary metastases after tumor-positive sentinel node biopsy in breast cancer. The predictive model performed well in internal and external validation but needs to be further studied in each center before application to clinical use.
authors.affiliation: Helsinki University Central Hospital, Breast Surgery Unit, PO Box 140, FI-00029 HUS, Finland. tuomo.meretoja@fimnet.fi
authors.forename: Tuomo J
authors.initials: TJ
authors.lastname: Meretoja
authors.forename: Marjut H K
authors.initials: MH
authors.lastname: Leidenius
authors.forename: Päivi S
authors.initials: PS
authors.lastname: Heikkilä
authors.forename: Gabor
authors.initials: G
authors.lastname: Boross
authors.forename: István
authors.initials: I
authors.lastname: Sejben
authors.forename: Peter
authors.initials: P
authors.lastname: Regitnig
authors.forename: Gero
authors.initials: G
authors.lastname: Luschin-Ebengreuth
authors.forename: Janez
authors.initials: J
authors.lastname: Žgajnar
authors.forename: Andraz
authors.initials: A
authors.lastname: Perhavec
authors.forename: Barbara
authors.initials: B
authors.lastname: Gazic
authors.forename: György
authors.initials: G
authors.lastname: Lázár
authors.forename: Tibor
authors.initials: T
authors.lastname: Takács
authors.forename: Andras
authors.initials: A
authors.lastname: Vörös
authors.forename: Zuhair A
authors.initials: ZA
authors.lastname: Saidan
authors.forename: Rana M
authors.initials: RM
authors.lastname: Nadeem
authors.forename: Isabella
authors.initials: I
authors.lastname: Castellano
authors.forename: Anna
authors.initials: A
authors.lastname: Sapino
authors.forename: Simonetta
authors.initials: S
authors.lastname: Bianchi
authors.forename: Vania
authors.initials: V
authors.lastname: Vezzosi
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Barranger
authors.forename: Ruben
authors.initials: R
authors.lastname: Lousquy
authors.forename: Riccardo
authors.initials: R
authors.lastname: Arisio
authors.forename: Maria Pia
authors.initials: MP
authors.lastname: Foschini
authors.forename: Shigeru
authors.initials: S
authors.lastname: Imoto
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kamma
authors.forename: Tove F
authors.initials: TF
authors.lastname: Tvedskov
authors.forename: Niels
authors.initials: N
authors.lastname: Kroman
authors.forename: Maj-Brit
authors.initials: MB
authors.lastname: Jensen
authors.forename: Riccardo A
authors.initials: RA
authors.lastname: Audisio
authors.forename: Gabor
authors.initials: G
authors.lastname: Cserni
mesh_terms: D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D019540:Area Under Curve; D001365:Axilla; D001943:Breast Neoplasms / Q000473:pathology* / Q000601:surgery*; D018270:Carcinoma, Ductal, Breast / Q000473:pathology / Q000556:secondary / Q000601:surgery*; D018275:Carcinoma, Lobular / Q000473:pathology / Q000556:secondary / Q000601:surgery*; D015986:Confounding Factors, Epidemiologic; D005060:Europe; D005260:Female; D005629:Frozen Sections; D006801:Humans; D007150:Immunohistochemistry; D007391:International Cooperation; D016015:Logistic Models; D008197:Lymph Node Excision; D008198:Lymph Nodes / Q000473:pathology*; D008207:Lymphatic Metastasis / Q000175:diagnosis; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D016017:Odds Ratio; D011237:Predictive Value of Tests; D012372:ROC Curve; D015203:Reproducibility of Results; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D021701:Sentinel Lymph Node Biopsy