title: Measurement of residual breast cancer burden to predict survival after neoadjuvant chemotherapy.
abstract: OBJECTIVE
  To measure residual disease after neoadjuvant chemotherapy in order to improve the prognostic information that can be obtained from evaluating pathologic response.
  
  
  METHODS
  Pathologic slides and reports were reviewed from 382 patients in two different treatment cohorts: sequential paclitaxel (T) then fluorouracil, doxorubicin, and cyclophosphamide (FAC) in 241 patients; and a single regimen of FAC in 141 patients. Residual cancer burden (RCB) was calculated as a continuous index combining pathologic measurements of primary tumor (size and cellularity) and nodal metastases (number and size) for prediction of distant relapse-free survival (DRFS) in multivariate Cox regression analyses.
  
  
  RESULTS
  RCB was independently prognostic in a multivariate model that included age, pretreatment clinical stage, hormone receptor status, hormone therapy, and pathologic response (pathologic complete response [pCR] v residual disease [RD]; hazard ratio = 2.50; 95% CI 1.70 to 3.69; P < .001). Minimal RD (RCB-I) in 17% of patients carried the same prognosis as pCR (RCB-0). Extensive RD (RCB-III) in 13% of patients was associated with poor prognosis, regardless of hormone receptor status, adjuvant hormone therapy, or pathologic American Joint Committee on Cancer stage of residual disease. The generalizability of RCB for prognosis of distant relapse was confirmed in the FAC-treated validation cohort.
  
  
  CONCLUSIONS
  RCB determined from routine pathologic materials represented the distribution of RD, was a significant predictor of DRFS, and can be used to define categories of near-complete response and chemotherapy resistance.
authors.affiliation: Department of Pathology, Unit 85, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030-4009, USA. fsymmans@mdanderson.org
authors.forename: W Fraser
authors.initials: WF
authors.lastname: Symmans
authors.forename: Florentia
authors.initials: F
authors.lastname: Peintinger
authors.forename: Christos
authors.initials: C
authors.lastname: Hatzis
authors.forename: Radhika
authors.initials: R
authors.lastname: Rajan
authors.forename: Henry
authors.initials: H
authors.lastname: Kuerer
authors.forename: Vicente
authors.initials: V
authors.lastname: Valero
authors.forename: Lina
authors.initials: L
authors.lastname: Assad
authors.forename: Anna
authors.initials: A
authors.lastname: Poniecka
authors.forename: Bryan
authors.initials: B
authors.lastname: Hennessy
authors.forename: Marjorie
authors.initials: M
authors.lastname: Green
authors.forename: Aman U
authors.initials: AU
authors.lastname: Buzdar
authors.forename: S Eva
authors.initials: SE
authors.lastname: Singletary
authors.forename: Gabriel N
authors.initials: GN
authors.lastname: Hortobagyi
authors.forename: Lajos
authors.initials: L
authors.lastname: Pusztai
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001365:Axilla; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis / Q000473:pathology; D008875:Middle Aged; D015999:Multivariate Analysis; D020360:Neoadjuvant Therapy; D018365:Neoplasm, Residual / Q000473:pathology*; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models