title: Prediction of Response to Neoadjuvant Chemotherapy Using Core Needle Biopsy Samples with the Prosigna Assay.
abstract: OBJECTIVE
  Most hormone receptor (HR)(+)/HER2(-) breast cancer patients respond unfavorably to neoadjuvant chemotherapy (NAC); however, genomic tests may identify those patients who are likely to benefit. Using the Prosigna assay, we first evaluated the technical performance of core needle biopsy (CNB) tissues. We then determined whether Prosigna risk of relapse (ROR) score and intrinsic subtype predicted response to NAC in HR(+)/HER2(-) patients using CNB samples.
  
  
  METHODS
  Using the NanoString's nCounter Dx analysis system and a development tissue sample set, we established tissue requirements and assay output variance. We then evaluated the concordance in subtype and correlation in ROR between CNBs and corresponding surgical resection specimens (SRS) in a second independent sample set. Finally, we analyzed 180 independent CNB samples from HR(+)/HER2(-) patients who were treated with NAC and correlated ROR and intrinsic subtype with pathologic response.
  
  
  RESULTS
  Intra- and interbiopsy variabilities were 2.2 and 6.8 ROR units, respectively. Subtype concordance within multiple CNBs was high for the 4- and 3-subtype classifications (k = 0.885 and 0.889, respectively). Correlation in Prosigna ROR score observed between paired CNBs and SRS was high (r ≥ 0.90), and subtype concordance was also high for the 4- and 3-subtype classifications (kappa = 0.81 and 0.91, respectively). Prosigna results obtained from the HR(+)/HER2(-) patient samples showed that both ROR (P = 0.047) and intrinsic subtype (OR LumA vs. non-LumA = 0.341, P = 0.037) were significant predictors of response to NAC.
  
  
  CONCLUSIONS
  Prosigna ROR and intrinsic subtype are readily obtained from CNB samples in normal practice and reliably predict response to NAC in HR(+)/HER2(-) patients.
authors.affiliation: Translational Genomics Group, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain. Medical Oncology Department, Hospital Clínic, Universitat de Barcelona, Barcelona, Spain. aprat@vhio.net.
authors.forename: Aleix
authors.initials: A
authors.lastname: Prat
authors.affiliation: Translational Genomics Group, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain.
authors.forename: Patricia
authors.initials: P
authors.lastname: Galván
authors.affiliation: University Hospital Regional and Virgen de la Victoria of Malaga, Malaga, Spain.
authors.forename: Begoña
authors.initials: B
authors.lastname: Jimenez
authors.affiliation: NanoString Technologies, Seattle, Washington.
authors.forename: Wesley
authors.initials: W
authors.lastname: Buckingham
authors.affiliation: NanoString Technologies, Seattle, Washington.
authors.forename: H Arthur
authors.initials: HA
authors.lastname: Jeiranian
authors.affiliation: NanoString Technologies, Seattle, Washington.
authors.forename: Carl
authors.initials: C
authors.lastname: Schaper
authors.affiliation: Translational Genomics Group, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain. Medical Oncology Department, Hospital Clínic, Universitat de Barcelona, Barcelona, Spain.
authors.forename: Maria
authors.initials: M
authors.lastname: Vidal
authors.affiliation: University Hospital Regional and Virgen de la Victoria of Malaga, Malaga, Spain.
authors.forename: Martina
authors.initials: M
authors.lastname: Álvarez
authors.affiliation: Department of Pathology, Hospital Universitari de la Vall d'Hebron, Barcelona, Spain.
authors.forename: Sherley
authors.initials: S
authors.lastname: Díaz
authors.affiliation: GlaxoSmithKline, Collegeville, Pennsylvania.
authors.forename: Catherine
authors.initials: C
authors.lastname: Ellis
authors.affiliation: Molecular Oncology Group, VHIO, Barcelona, Spain.
authors.forename: Paolo
authors.initials: P
authors.lastname: Nuciforo
authors.affiliation: NanoString Technologies, Seattle, Washington.
authors.forename: Sean
authors.initials: S
authors.lastname: Ferree
authors.affiliation: University Hospital Regional and Virgen de la Victoria of Malaga, Malaga, Spain.
authors.forename: Nuria
authors.initials: N
authors.lastname: Ribelles
authors.affiliation: Medical Oncology Department, Hospital Clínic, Universitat de Barcelona, Barcelona, Spain.
authors.forename: Barbara
authors.initials: B
authors.lastname: Adamo
authors.affiliation: Department of Pathology, Hospital Universitari de la Vall d'Hebron, Barcelona, Spain.
authors.forename: Santiago
authors.initials: S
authors.lastname: Ramón Y Cajal
authors.affiliation: Department of Pathology, Hospital Universitari de la Vall d'Hebron, Barcelona, Spain.
authors.forename: Vicente
authors.initials: V
authors.lastname: Peg
authors.affiliation: University Hospital Regional and Virgen de la Victoria of Malaga, Malaga, Spain.
authors.forename: Emilio
authors.initials: E
authors.lastname: Alba
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor; D062005:Biopsy, Large-Core Needle; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D005260:Female; D006801:Humans; D020360:Neoadjuvant Therapy; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D057285:Precision Medicine / Q000379:methods; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D015203:Reproducibility of Results; D016896:Treatment Outcome; D047368:Tumor Burden
chemical_list: D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone