title: Nottingham Clinico-Pathological Response Index (NPRI) after neoadjuvant chemotherapy (Neo-ACT) accurately predicts clinical outcome in locally advanced breast cancer.
abstract: OBJECTIVE
  There is a need to identify more sensitive clinicopathologic criteria to assess the response to neoadjuvant chemotherapy (Neo-ACT) and guide subsequent adjuvant therapy.
  
  
  METHODS
  We performed a clinicopathologic assessment of 426 patients who had completed Neo-ACT for locally advanced breast cancer (LABC) with a median follow-up of 70 months. Patients were divided into a training set treated with anthracycline combination chemotherapy (n = 172); an internal validation set treated with anthracycline and taxane (n = 129); and an external validation set treated with anthracycline with or without taxane (n = 125).
  
  
  RESULTS
  A multivariate Cox regression model demonstrated the absence of fibrosis, presence of lymphovascular invasion, increasing number of lymph node metastases, and administration of hormone therapy were significantly associated with short breast cancer-specific survival (BCSS) and disease-free survival (DFS); Ps < 0.01, while reduction of tumor size was associated with DFS (P = 0.022). Nottingham Clinico-Pathological Response Indexes (NPRI) were calculated, and four prognostic groups (NPRI-PG) were identified. Patients in prognostic group 2 (NPRI-PG2) for BCSS (66 of 172; 38.4%) have the same prognosis as those who achieved pathologic complete response (pCR; NPRI-PG1; 15%). Receiver-operating characteristic (ROC) curves indicated that the NPRI outperformed the currently used prognostic factors and adding the NPRI improved their performance as a predictor for both BCSS (area under the curve [AUC], 0.88) and DFS (AUC, 0.87).
  
  
  CONCLUSIONS
  The NPRI predicts BCSS and DFS, with a higher sensitivity than pCR. The NPRI can also improve the sensitivity and specificity of clinicopathologic response as a study endpoint, for assessing response to Neo-ACT, and can serve as a valuable tool for the discovery of future predictive molecular markers.
authors.affiliation: Department of Clinical Oncology, Nottingham University Hospitals, Nottingham, United Kingdom.
authors.forename: Tarek M
authors.initials: TM
authors.lastname: Abdel-Fatah
authors.affiliation: School of Science and Technology, Nottingham Trent University, Nottingham, United Kingdom.
authors.forename: Graham
authors.initials: G
authors.lastname: Ball
authors.affiliation: Histopathology Department, Nottingham University Hospitals NHS Trust, Nottingham, United Kingdom.
authors.forename: Andrew H S
authors.initials: AH
authors.lastname: Lee
authors.affiliation: School of Medicine, Department of Research Oncology, King's College London, London, United Kingdom.
authors.forename: Sarah
authors.initials: S
authors.lastname: Pinder
authors.affiliation: Surgical Department, Nottingham University Hospitals, Nottingham, United Kingdom.
authors.forename: R Douglas
authors.initials: RD
authors.lastname: MacMilan
authors.affiliation: Radiology Department, Nottingham University Hospitals, Nottingham, United Kingdom.
authors.forename: Eleanor
authors.initials: E
authors.lastname: Cornford
authors.affiliation: Department of Clinical Oncology, Nottingham University Hospitals, Nottingham, United Kingdom.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Moseley
authors.affiliation: Department of Clinical Oncology, Nottingham University Hospitals, Nottingham, United Kingdom.
authors.forename: Rafael
authors.initials: R
authors.lastname: Silverman
authors.affiliation: Department of Clinical Oncology, Nottingham University Hospitals, Nottingham, United Kingdom.
authors.forename: James
authors.initials: J
authors.lastname: Price
authors.affiliation: Western Diagnostics, Perth, Western Australia, Australia.
authors.forename: Bruce
authors.initials: B
authors.lastname: Latham
authors.affiliation: Western Diagnostics, Perth, Western Australia, Australia.
authors.forename: David
authors.initials: D
authors.lastname: Palmer
authors.affiliation: Curtin Health Innovation Research Institute, Curtin University, Perth, Western Australia, Australia.
authors.forename: Arlene
authors.initials: A
authors.lastname: Chan
authors.affiliation: Histopathology Department, Nottingham University Hospitals NHS Trust, Nottingham, United Kingdom.
authors.forename: Ian O
authors.initials: IO
authors.lastname: Ellis
authors.affiliation: Department of Clinical Oncology, Nottingham University Hospitals, Nottingham, United Kingdom. steve.chan@nuh.nhs.uk.
authors.forename: Stephen Y T
authors.initials: SY
authors.lastname: Chan
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D019540:Area Under Curve; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D015233:Models, Statistical; D020360:Neoadjuvant Therapy; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011379:Prognosis; D012372:ROC Curve; D012307:Risk Factors; D016896:Treatment Outcome; D047368:Tumor Burden
chemical_list: D014408:Biomarkers, Tumor