title: A model to predict pathologic complete response of axillary lymph nodes to neoadjuvant chemo(immuno)therapy in patients with clinically node-positive breast cancer.
abstract: BACKGROUND
  Between 20% and 42% of patients with clinically node-positive breast cancer achieve a pathologic complete response (pCR) of axillary lymph nodes after neoadjuvant chemotherapy or immunotherapy, or both, (chemo[immuno]therapy). Hypothetically, axillary lymph node dissection (ALND) may be safely omitted in these patients. This study aimed to develop a model for predicting axillary pCR in these patients.
  
  
  METHODS
  We retrospectively identified patients with clinically node-positive breast cancer who were treated with neoadjuvant chemo(immuno)therapy and ALND between 2005 and 2012 in 5 hospitals. Patient and tumor characteristics, neoadjuvant chemo(immuno)therapy regimens, and pathology reports were extracted. Binary logistic regression analysis was used to predict axillary pCR with the following variables: age, tumor stage and type, hormone receptor and human epidermal growth factor receptor 2 (HER2) status, and administration of taxane and trastuzumab. The model was internally validated by bootstrap resampling. The overall performance of the model was assessed by the Brier score and the discriminative performance by receiver operating characteristic (ROC) curve analysis.
  
  
  RESULTS
  A model was developed based on 291 patients and was internally validated with a scaled Brier score of 0.14. The area under the ROC curve of this model was 0.77 (95% confidence interval [CI], 0.71-0.82). At a cutoff value of predicted probability ≥ 0.50, the model demonstrated specificity of 88%, sensitivity of 43%, positive predictive value (PPV) of 65%, and negative predictive value (NPV) of 75%.
  
  
  CONCLUSIONS
  This prediction model shows reasonable accuracy for predicting axillary pCR. However, omitting axillary treatment based solely on the nomogram score is not justified. Further research is warranted to noninvasively identify patients with axillary pCR.
authors.affiliation: Department of Radiology, Maastricht University Medical Center+, Maastricht, The Netherlands; Department of Surgery, Maastricht University Medical Center+, Maastricht, The Netherlands; GROW School for Oncology and Developmental Biology, Maastricht, The Netherlands. Electronic address: info@rjschipper.nl.
authors.forename: Robert-Jan
authors.initials: RJ
authors.lastname: Schipper
authors.affiliation: Department of Surgery, Maastricht University Medical Center+, Maastricht, The Netherlands; GROW School for Oncology and Developmental Biology, Maastricht, The Netherlands.
authors.forename: Martine
authors.initials: M
authors.lastname: Moossdorff
authors.affiliation: Department of Epidemiology, Maastricht University Medical Center+, Maastricht, The Netherlands.
authors.forename: Patty J
authors.initials: PJ
authors.lastname: Nelemans
authors.affiliation: Department of Surgery, Catharina Hospital Eindhoven, Eindhoven, The Netherlands.
authors.forename: Grard A P
authors.initials: GA
authors.lastname: Nieuwenhuijzen
authors.affiliation: Department of Pathology, Maastricht University Medical Center+, Maastricht, The Netherlands.
authors.forename: Bart
authors.initials: B
authors.lastname: de Vries
authors.affiliation: Department of Surgery, Canisius Wilhelmina Hospital, Nijmegen, The Netherlands.
authors.forename: Luc J A
authors.initials: LJ
authors.lastname: Strobbe
authors.affiliation: Department of Surgery, Máxima Medical Center, Veldhoven, The Netherlands.
authors.forename: Rudi M H
authors.initials: RM
authors.lastname: Roumen
authors.affiliation: Department of Internal Medicine, Atrium Medical Center (Parkstad), Heerlen, The Netherlands.
authors.forename: Franchette
authors.initials: F
authors.lastname: van den Berkmortel
authors.affiliation: Division of Medical Oncology, Maastricht University Medical Center+, Maastricht, The Netherlands; GROW School for Oncology and Developmental Biology, Maastricht, The Netherlands.
authors.forename: Vivianne C G
authors.initials: VC
authors.lastname: Tjan-Heijnen
authors.affiliation: Department of Radiology, Maastricht University Medical Center+, Maastricht, The Netherlands; GROW School for Oncology and Developmental Biology, Maastricht, The Netherlands.
authors.forename: Regina G H
authors.initials: RG
authors.lastname: Beets-Tan
authors.affiliation: Department of Radiology, Maastricht University Medical Center+, Maastricht, The Netherlands; GROW School for Oncology and Developmental Biology, Maastricht, The Netherlands.
authors.forename: Marc B I
authors.initials: MB
authors.lastname: Lobbes
authors.affiliation: Department of Surgery, Maastricht University Medical Center+, Maastricht, The Netherlands; GROW School for Oncology and Developmental Biology, Maastricht, The Netherlands.
authors.forename: Marjolein L
authors.initials: ML
authors.lastname: Smidt
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D019540:Area Under Curve; D001365:Axilla; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D005260:Female; D006801:Humans; D007167:Immunotherapy; D008198:Lymph Nodes / Q000473:pathology*; D008207:Lymphatic Metastasis; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging / Q000379:methods*; D049451:Nomograms; D012372:ROC Curve; D012189:Retrospective Studies; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents
keywords: Axillary lymph node dissection; Axillary lymph node metastases; Breast cancer; Neoadjuvant systemic therapy; Prediction model