title: Response and survival of breast cancer intrinsic subtypes following multi-agent neoadjuvant chemotherapy.
abstract: BACKGROUND
  Predicting treatment benefit and/or outcome before any therapeutic intervention has taken place would be clinically very useful. Herein, we evaluate the ability of the intrinsic subtypes and the risk of relapse score at diagnosis to predict survival and response following neoadjuvant chemotherapy. In addition, we evaluated the ability of the Claudin-low and 7-TNBCtype classifications to predict response within triple-negative breast cancer (TNBC).
  
  
  METHODS
  Gene expression and clinical-pathological data were evaluated in a combined dataset of 957 breast cancer patients, including 350 with TNBC, treated with sequential anthracycline and anti-microtubule-based neoadjuvant regimens. Intrinsic subtype, risk of relapse score based on subtype and proliferation (ROR-P), the Claudin-low subtype and the 7-TNBCtype subtype classification were evaluated. Logistic regression models for pathological complete response (pCR) and Cox models for distant relapse-free survival (DRFS) were used.
  
  
  RESULTS
  Basal-like, Luminal A, Luminal B, and HER2-enriched subtypes represented 32.7%, 30.6%, 18.2%, and 10.3% of cases, respectively. Intrinsic subtype was independently associated with pCR in all patients, in hormone receptor-positive/HER2-negative disease, in HER2-positive disease, and in TNBC. The pCR rate of Basal-like disease was >35% across all clinical cohorts. Neither the Claudin-low nor the 7-TNBCtype subtype classifications predicted pCR within TNBCs after accounting for intrinsic subtype. Finally, intrinsic subtype and ROR-P provided independent prognostic information beyond clinicopathological variables and type of pathological response. A 5-year DRFS of 97.5% (92.8-100.0%) was observed in these neoadjuvant-treated and clinically node-negative patients predicted to be low risk by ROR-P (i.e. 57.4% of Luminal A tumors with clinically node-negative disease).
  
  
  CONCLUSIONS
  Intrinsic subtyping at diagnosis provides prognostic and predictive information for patients receiving neoadjuvant chemotherapy. Although we could not exclude a survival benefit of neoadjuvant chemotherapy in patients with early breast cancer with clinically node-negative and ROR-low disease at diagnosis, the absolute benefit of cytotoxic therapy in this group might be rather small (if any).
authors.affiliation: Translational Genomics Group, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain. alprat@clinic.ub.es.|Translational Genomics and Targeted Therapeutics in Solid Tumors, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Rosselló, 149, 08036, Barcelona, Spain. alprat@clinic.ub.es.|Department of Medical Oncology, Hospital Clínic de Barcelona, Barcelona, Spain. alprat@clinic.ub.es.
authors.forename: Aleix
authors.initials: A
authors.lastname: Prat
authors.affiliation: Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: Cheng
authors.initials: C
authors.lastname: Fan
authors.affiliation: Translational Genomics and Targeted Therapeutics in Solid Tumors, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Rosselló, 149, 08036, Barcelona, Spain.|Department of Medical Oncology, Hospital Clínic de Barcelona, Barcelona, Spain.
authors.forename: Aranzazu
authors.initials: A
authors.lastname: Fernández
authors.affiliation: Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Hoadley
authors.affiliation: Translational Genomics and Targeted Therapeutics in Solid Tumors, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Rosselló, 149, 08036, Barcelona, Spain.|Department of Medical Oncology, Hospital Clínic de Barcelona, Barcelona, Spain.
authors.forename: Rossella
authors.initials: R
authors.lastname: Martinello
authors.affiliation: Translational Genomics Group, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain.
authors.forename: Maria
authors.initials: M
authors.lastname: Vidal
authors.affiliation: Translational Genomics and Targeted Therapeutics in Solid Tumors, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Rosselló, 149, 08036, Barcelona, Spain.|Department of Medical Oncology, Hospital Clínic de Barcelona, Barcelona, Spain.
authors.forename: Margarita
authors.initials: M
authors.lastname: Viladot
authors.affiliation: Translational Genomics and Targeted Therapeutics in Solid Tumors, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Rosselló, 149, 08036, Barcelona, Spain.|Department of Medical Oncology, Hospital Clínic de Barcelona, Barcelona, Spain.
authors.forename: Estela
authors.initials: E
authors.lastname: Pineda
authors.affiliation: Translational Genomics and Targeted Therapeutics in Solid Tumors, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Rosselló, 149, 08036, Barcelona, Spain.|Department of Medical Oncology, Hospital Clínic de Barcelona, Barcelona, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Arance
authors.affiliation: Translational Genomics and Targeted Therapeutics in Solid Tumors, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Rosselló, 149, 08036, Barcelona, Spain.|Department of Medical Oncology, Hospital Clínic de Barcelona, Barcelona, Spain.
authors.forename: Montserrat
authors.initials: M
authors.lastname: Muñoz
authors.affiliation: Translational Genomics and Targeted Therapeutics in Solid Tumors, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Rosselló, 149, 08036, Barcelona, Spain.|Department of Medical Oncology, Hospital Clínic de Barcelona, Barcelona, Spain.
authors.forename: Laia
authors.initials: L
authors.lastname: Paré
authors.affiliation: Clinical Trials & Statistics Unit, The Institute of Cancer Research, Belmont, UK.
authors.forename: Maggie C U
authors.initials: MC
authors.lastname: Cheang
authors.affiliation: Translational Genomics and Targeted Therapeutics in Solid Tumors, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Rosselló, 149, 08036, Barcelona, Spain.|Department of Medical Oncology, Hospital Clínic de Barcelona, Barcelona, Spain.
authors.forename: Barbara
authors.initials: B
authors.lastname: Adamo
authors.affiliation: Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA.|Department of Genetics, University of North Carolina, Chapel Hill, NC, USA.|Department of Pathology & Laboratory Medicine, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: Charles M
authors.initials: CM
authors.lastname: Perou
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D015331:Cohort Studies; D005260:Female; D015870:Gene Expression; D006801:Humans; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D011379:Prognosis; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality