title: A genomic predictor of response and survival following taxane-anthracycline chemotherapy for invasive breast cancer.
abstract: BACKGROUND
  Prediction of high probability of survival from standard cancer treatments is fundamental for individualized cancer treatment strategies.
  
  
  OBJECTIVE
  To develop a predictor of response and survival from chemotherapy for newly diagnosed invasive breast cancer.
  
  
  METHODS
  Prospective multicenter study conducted from June 2000 to March 2010 at the M. D. Anderson Cancer Center to develop and test genomic predictors for neoadjuvant chemotherapy. Patients were those with newly diagnosed ERBB2 (HER2 or HER2/neu)-negative breast cancer treated with chemotherapy containing sequential taxane and anthracycline-based regimens (then endocrine therapy if estrogen receptor [ER]-positive). Different predictive signatures for resistance and response to preoperative (neoadjuvant) chemotherapy (stratified according to ER status) were developed from gene expression microarrays of newly diagnosed breast cancer (310 patients). Breast cancer treatment sensitivity was then predicted using the combination of signatures for (1) sensitivity to endocrine therapy, (2) chemoresistance, and (3) chemosensitivity, with independent validation (198 patients) and comparison with other reported genomic predictors of chemotherapy response.
  
  
  METHODS
  Distant relapse-free survival (DRFS) if predicted treatment sensitive and absolute risk reduction ([ARR], difference in DRFS between 2 predicted groups) at median follow-up (3 years).
  
  
  RESULTS
  Patients in the independent validation cohort (99% clinical stage II-III) who were predicted to be treatment sensitive (28%) had 56% (95% CI, 31%-78%) probability of excellent pathologic response and DRFS of 92% (95% CI, 85%-100%), with an ARR of 18% (95% CI, 6%-28%). Survival was predicted in ER-positive (30% predicted sensitive; DRFS, 97% [95% CI, 91%-100%]; ARR, 11% [95% CI, 0.1%-21%]) and ER-negative (26% predicted sensitive; DRFS, 83% [95% CI, 68%-100%]; ARR, 26% [95% CI, 4%-48%]) subsets and was significant in multivariate analysis. Other genomic predictors showed paradoxically worse survival for patients predicted to be responsive to chemotherapy.
  
  
  CONCLUSIONS
  A genomic predictor combining ER status, predicted chemoresistance, predicted chemosensitivity, and predicted endocrine sensitivity identified patients with high probability of survival following taxane and anthracycline chemotherapy.
authors.affiliation: Nuvera Biosciences Inc, Woburn, Massachusetts, USA.
authors.forename: Christos
authors.initials: C
authors.lastname: Hatzis
authors.forename: Lajos
authors.initials: L
authors.lastname: Pusztai
authors.forename: Vicente
authors.initials: V
authors.lastname: Valero
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Booser
authors.forename: Laura
authors.initials: L
authors.lastname: Esserman
authors.forename: Ana
authors.initials: A
authors.lastname: Lluch
authors.forename: Tatiana
authors.initials: T
authors.lastname: Vidaurre
authors.forename: Frankie
authors.initials: F
authors.lastname: Holmes
authors.forename: Eduardo
authors.initials: E
authors.lastname: Souchon
authors.forename: Hongkun
authors.initials: H
authors.lastname: Wang
authors.forename: Miguel
authors.initials: M
authors.lastname: Martin
authors.forename: José
authors.initials: J
authors.lastname: Cotrina
authors.forename: Henry
authors.initials: H
authors.lastname: Gomez
authors.forename: Rebekah
authors.initials: R
authors.lastname: Hubbard
authors.forename: J Ignacio
authors.initials: JI
authors.lastname: Chacón
authors.forename: Jaime
authors.initials: J
authors.lastname: Ferrer-Lozano
authors.forename: Richard
authors.initials: R
authors.lastname: Dyer
authors.forename: Meredith
authors.initials: M
authors.lastname: Buxton
authors.forename: Yun
authors.initials: Y
authors.lastname: Gong
authors.forename: Yun
authors.initials: Y
authors.lastname: Wu
authors.forename: Nuhad
authors.initials: N
authors.lastname: Ibrahim
authors.forename: Eleni
authors.initials: E
authors.lastname: Andreopoulou
authors.forename: Naoto T
authors.initials: NT
authors.lastname: Ueno
authors.forename: Kelly
authors.initials: K
authors.lastname: Hunt
authors.forename: Wei
authors.initials: W
authors.lastname: Yang
authors.forename: Arlene
authors.initials: A
authors.lastname: Nazario
authors.forename: Angela
authors.initials: A
authors.lastname: DeMichele
authors.forename: Joyce
authors.initials: J
authors.lastname: O'Shaughnessy
authors.forename: Gabriel N
authors.initials: GN
authors.lastname: Hortobagyi
authors.forename: W Fraser
authors.initials: WF
authors.lastname: Symmans
mesh_terms: D000328:Adult; D000465:Algorithms; D018943:Anthracyclines / Q000627:therapeutic use; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001707:Biopsy, Needle; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality; D001952:Bridged-Ring Compounds / Q000627:therapeutic use; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D005260:Female; D005544:Forecasting; D020869:Gene Expression Profiling; D052138:Genes, Neoplasm / Q000235:genetics*; D018734:Genes, erbB-2; D023281:Genomics; D006801:Humans; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009364:Neoplasm Recurrence, Local; D020411:Oligonucleotide Array Sequence Analysis; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D011960:Receptors, Estrogen / Q000032:analysis; D012306:Risk; D043823:Taxoids / Q000627:therapeutic use
chemical_list: D018943:Anthracyclines; D018931:Antineoplastic Agents, Hormonal; D001952:Bridged-Ring Compounds; D011960:Receptors, Estrogen; D043823:Taxoids; C080625:taxane