International multicenter tool to predict the risk of four or more tumor-positive axillary lymph nodes in breast cancer patients with sentinel node macrometastases

Tuomo J. Meretoja, R. A. Audisio, P. S. Heikkilä, R. Bori, I. Sejben, P. Regitnig, G. Luschin-Ebengreuth, J. Zgajnar, A. Perhavec, B. Gazic, G. Lázár, T. Takács, B. Koẃvari, Z. A. Saidan, R. M. Nadeem, I. Castellano, A. Sapino, S. Bianchi, V. Vezzosi, E. BarrangerR. Lousquy, R. Arisio, M. P. Foschini, S. Imoto, H. Kamma, T. F. Tvedskov, M. B. Jensen, G. Cserni, M. H K Leidenius

Research output: Contribution to journalArticlepeer-review


Recently, many centers have omitted routine axillary lymph node dissection (ALND) after metastatic sentinel node biopsy in breast cancer due to a growing body of literature. However, existing guidelines of adjuvant treatment planning are strongly based on axillary nodal stage. In this study, we aim to develop a novel international multicenter predictive tool to estimate a patient-specific risk of having four or more tumor-positive axillary lymph nodes (ALN) in patients with macrometastatic sentinel node(s) (SN). A series of 675 patients with macrometastatic SN and completion ALND from five European centers were analyzed by logistic regression analysis. A multivariate predictive model was created and validated internally by 367 additional patients and then externally by 760 additional patients from eight different centers. All statistical tests were two-sided. Prevalence of four or more tumor-positive ALN in each center's series (P = 0.010), number of metastatic SNs (P <0.0001), number of negative SNs (P = 0.003), histological size of the primary tumor (P = 0.020), and extra-capsular extension of SN metastasis (P <0.0001) were included in the predictive model. The model's area under the receiver operating characteristics curve was 0.766 in the internal validation and 0.774 in external validation. Our novel international multicenter-based predictive tool reliably estimates the risk of four or more axillary metastases after identifying macrometastatic SN(s) in breast cancer. Our tool performs well in internal and external validation, but needs to be further validated in each center before application to clinical use.

Original languageEnglish
Pages (from-to)817-827
Number of pages11
JournalBreast Cancer Research and Treatment
Issue number3
Publication statusPublished - Apr 2013


  • Axillary lymph node dissection
  • Breast cancer
  • Sentinel node biopsy
  • Tumor staging

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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