Axillary lymph node nanometastases are prognostic factors for disease-free survival and metastatic relapse in breast cancer patients

Patrizia Querzoli, Massimo Pedriali, Rosa Rinaldi, Anna Rita Lombardi, Elia Biganzoli, Patrizia Boracchi, Stefano Ferretti, Claudia Frasson, Caterina Zanella, Sara Ghisellini, Federico Ambrogi, Laura Antolini, Mauro Piantelli, Stefano Iacobelli, Ettore Marubini, Saverio Alberti, Italo Nenci

Research output: Contribution to journalArticlepeer-review


Purpose: Early breast cancer presents with a remarkable heterogeneity of outcomes. Undetected, microscopic lymph node tumor deposits may account for a significant fraction of this prognostic diversity. Thus, we systematically evaluated the presence of lymph node tumor cell deposits ≤0.2 mm in diameter [pN0(i+), nanometastases] and analyzed their prognostic effect. Experimental Design: Single-institution, consecutive patients with 8 years of median follow-up (n = 702) were studied. To maximize chances of detecting micrometastases and nanometastases, whole-axilla dissections were analyzed. pN0 cases (n = 377) were systematically reevaluated by lymph node (n = 6676) step-sectioning and anticytokeratin immunohistochemical analysis. The risk of first adverse events and of distant relapse of bona fide pN0 patients was compared with that of pN0(i+), pN1mi, and PN1 cases. Results: Minimal lymph node deposits were revealed in 13% of pN0 patients. The hazard ratio for all adverse events of pN 0(i+) versus pN0(i-) was 2.51 (P = 0.00019). Hazards of pN1mi and pN0(i+) cases were not significantly different. A multivariate Cox model showed a hazard ratio of 2.16 for grouped pN 0(i+)/pN1mi versus pN0(i-) (P = 0.0005). Crude cumulative incidence curves for metastatic relapse were also significantly different (Gray's test χ2 = 5.54, P = 0.019). Conclusion: Nanometastases are a strong risk factor for disease-free survival and for metastatic relapse. These findings support the inclusion of procedures for nanometastasis detection in tumor-node-metastasis staging.

Original languageEnglish
Pages (from-to)6696-6701
Number of pages6
JournalClinical Cancer Research
Issue number22
Publication statusPublished - Nov 15 2006

ASJC Scopus subject areas

  • Cancer Research
  • Oncology


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