title: Axillary lymph node nanometastases are prognostic factors for disease-free survival and metastatic relapse in breast cancer patients.
abstract: OBJECTIVE
  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<or=0.2 mm in diameter [pN0(i+), nanometastases] and analyzed their prognostic effect.
  
  
  METHODS
  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 pN0(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 pN0(i+)/pN1mi versus pN0(i-) (P=0.0005). Crude cumulative incidence curves for metastatic relapse were also significantly different (Gray's test chi2=5.54, P=0.019).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Experimental and Diagnostic Medicine, Section of Anatomic Pathology, University of Ferrara, Ferrara, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Querzoli
authors.forename: Massimo
authors.initials: M
authors.lastname: Pedriali
authors.forename: Rosa
authors.initials: R
authors.lastname: Rinaldi
authors.forename: Anna Rita
authors.initials: AR
authors.lastname: Lombardi
authors.forename: Elia
authors.initials: E
authors.lastname: Biganzoli
authors.forename: Patrizia
authors.initials: P
authors.lastname: Boracchi
authors.forename: Stefano
authors.initials: S
authors.lastname: Ferretti
authors.forename: Claudia
authors.initials: C
authors.lastname: Frasson
authors.forename: Caterina
authors.initials: C
authors.lastname: Zanella
authors.forename: Sara
authors.initials: S
authors.lastname: Ghisellini
authors.forename: Federico
authors.initials: F
authors.lastname: Ambrogi
authors.forename: Laura
authors.initials: L
authors.lastname: Antolini
authors.forename: Mauro
authors.initials: M
authors.lastname: Piantelli
authors.forename: Stefano
authors.initials: S
authors.lastname: Iacobelli
authors.forename: Ettore
authors.initials: E
authors.lastname: Marubini
authors.forename: Saverio
authors.initials: S
authors.lastname: Alberti
authors.forename: Italo
authors.initials: I
authors.lastname: Nenci
mesh_terms: D000328:Adult; D000368:Aged; D001365:Axilla; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000628:therapy; D002277:Carcinoma / Q000175:diagnosis* / Q000628:therapy; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008197:Lymph Node Excision; D008198:Lymph Nodes / Q000473:pathology*; D008207:Lymphatic Metastasis / Q000175:diagnosis* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012008:Recurrence