title: Prognosis of residual axillary disease after neoadjuvant chemotherapy in clinically node-positive breast cancer patients: isolated tumor cells and micrometastases carry a better prognosis than macrometastases.
abstract: OBJECTIVE
  The aim of this study was to compare disease-free survival (DFS) and overall survival (OS) between clinically node-positive breast cancer patients, treated with neoadjuvant chemotherapy (NAC), with axillary pathologic complete response (ypN0), residual axillary isolated tumor cells or micrometastases (ypNitc/mi), and residual axillary macrometastases (ypN1-3).
  
  
  METHODS
  All patients diagnosed with clinically node-positive primary invasive breast cancer treated with NAC and subsequent axillary lymph node dissection between 2005 and 2008 were retrospectively analyzed. Data were obtained from the Netherlands Cancer Registry. Patients were stratified by final pathological axillary status: ypN0, ypNitc/mi, or ypN1-3. The main outcome measures DFS and OS were analyzed using Kaplan-Meier survival analysis. Uni- and multivariable cox regression analyses were used to determine independent predictors for DFS and OS.
  
  
  RESULTS
  A total of 1347 patients were included. Pathologic nodal status was ypN0 in 22.2%, ypNitc/mi in 3.8%, and ypN1-3 in 74.0% of patients. Overall, 5-year DFS was 57.8% and mean OS was 7.4 years. DFS and OS were comparable between ypN0 and ypNitc/mi (HR 1.38 (0.40-4.79, p = 0.613) and HR 0.92 (0.27-3.09, p = 0.889), respectively), but significantly different between ypN0 and ypN1-3 (HR 1.78 (1.06-3.00, p = 0.031) and HR 1.70 (1.07-2.71, p = 0.026), respectively).
  
  
  CONCLUSIONS
  Clinically node-positive patients, treated with NAC, with axillary nodal status ypN0 or ypNitc/mi carry similar prognosis regarding DFS and OS. Axillary nodal status ypN1-3 is associated with a less favorable prognosis. Future studies should consider ypN0 and ypNitc/mi as one entity.
authors.affiliation: Department of Radiology and Nuclear Medicine, Maastricht University Medical Center+, P.O. Box 5800, 6202 AZ, Maastricht, The Netherlands. Thiemovn@gmail.com.|Department of Surgery, Maastricht University Medical Center+, Maastricht, The Netherlands. Thiemovn@gmail.com.|GROW - School for Oncology and Developmental Biology, Maastricht University Medical Center+, Maastricht, The Netherlands. Thiemovn@gmail.com.
authors.forename: T J A
authors.initials: TJ
authors.lastname: van Nijnatten
authors.affiliation: Department of Surgery, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: J M
authors.initials: JM
authors.lastname: Simons
authors.affiliation: Department of Surgery, Maastricht University Medical Center+, Maastricht, The Netherlands.|GROW - School for Oncology and Developmental Biology, Maastricht University Medical Center+, Maastricht, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Moossdorff
authors.affiliation: Department of Research, Netherlands Comprehensive Cancer Organisation, Utrecht, The Netherlands.
authors.forename: L
authors.initials: L
authors.lastname: de Munck
authors.affiliation: Department of Radiology and Nuclear Medicine, Maastricht University Medical Center+, P.O. Box 5800, 6202 AZ, Maastricht, The Netherlands.
authors.forename: M B I
authors.initials: MB
authors.lastname: Lobbes
authors.affiliation: Department of Surgery, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: C C
authors.initials: CC
authors.lastname: van der Pol
authors.affiliation: Department of Surgical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
authors.forename: L B
authors.initials: LB
authors.lastname: Koppert
authors.affiliation: Department of Surgery, Amphia Hospital, Breda, The Netherlands.
authors.forename: E J T
authors.initials: EJ
authors.lastname: Luiten
authors.affiliation: Department of Surgery, Maastricht University Medical Center+, Maastricht, The Netherlands.|GROW - School for Oncology and Developmental Biology, Maastricht University Medical Center+, Maastricht, The Netherlands.
authors.forename: M L
authors.initials: ML
authors.lastname: Smidt
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001365:Axilla; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017024:Chemotherapy, Adjuvant / Q000379:methods; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology*; D008207:Lymphatic Metastasis; D020360:Neoadjuvant Therapy; D061206:Neoplasm Micrometastasis / Q000188:drug therapy* / Q000473:pathology; D018365:Neoplasm, Residual; D009426:Netherlands; D011379:Prognosis; D012042:Registries; D012189:Retrospective Studies; D016019:Survival Analysis; D016896:Treatment Outcome
keywords: Axillary lymph node; Breast cancer; Neoadjuvant chemotherapy; Prognosis