title: Chemosensitivity and Endocrine Sensitivity in Clinical Luminal Breast Cancer Patients in the Prospective Neoadjuvant Breast Registry Symphony Trial (NBRST) Predicted by Molecular Subtyping.
abstract: OBJECTIVE
  Hormone receptor-positive (HR+) tumors have heterogeneous biology and present a challenge for determining optimal treatment. In the Neoadjuvant Breast Registry Symphony Trial (NBRST) patients were classified according to MammaPrint/BluePrint subtyping to provide insight into the response to neoadjuvant endocrine therapy (NET) or neoadjuvant chemotherapy (NCT).
  
  
  OBJECTIVE
  The purpose of this predefined substudy was to compare MammaPrint/BluePrint with conventional 'clinical' immunohistochemistry/fluorescence in situ hybridization (IHC/FISH) subtyping in 'clinical luminal' [HR+/human epidermal growth factor receptor 2-negative (HER2-)] breast cancer patients to predict treatment sensitivity.
  
  
  METHODS
  NBRST IHC/FISH HR+/HER2- breast cancer patients (n = 474) were classified into four molecular subgroups by MammaPrint/BluePrint subtyping: Luminal A, Luminal B, HER2, and Basal type. Pathological complete response (pCR) rates were compared with conventional IHC/FISH subtype.
  
  
  RESULTS
  The overall pCR rate for 'clinical luminal' patients to NCT was 11 %; however, 87 of these 474 patients were reclassified as Basal type by BluePrint, with a high pCR rate of 32 %. The MammaPrint index was highly associated with the likelihood of pCR (p < 0.001). Fifty-three patients with BluePrint Luminal tumors received NET with an aromatase inhibitor and 36 (68 %) had a clinical response.
  
  
  CONCLUSIONS
  With BluePrint subtyping, 18 % of clinical 'luminal' patients are classified in a different subgroup, compared with conventional assessment, and these patients have a significantly higher response rate to NCT compared with BluePrint Luminal patients. MammaPrint/BluePrint subtyping can help allocate effective treatment to appropriate patients. In addition, accurate identification of subtype biology is important in the interpretation of neoadjuvant treatment response since lack of pCR in luminal patients does not portend the worse prognosis associated with residual disease in Basal and HER2 subtypes.
authors: Nashville Breast Center, Nashville, TN, USA. patwhitworth@gmail.com.
authors: Pat
authors: P
authors: Whitworth
authors: Dallas Surgical Group, Dallas, TX, USA.
authors: Peter
authors: P
authors: Beitsch
authors: Coastal Carolina Breast Center, Murrells Inlet, SC, USA.
authors: Angela
authors: A
authors: Mislowsky
authors: Virginia Breast Center, Bon Secours Cancer Institute, Richmond, VA, USA.
authors: James V
authors: JV
authors: Pellicane
authors: Northeast Georgia Medical Center, Gainesville, GA, USA.
authors: Charles
authors: C
authors: Nash
authors: Akron General Hospital, Akron, OH, USA.
authors: Mary
authors: M
authors: Murray
authors: Comprehensive Cancer Center, Palm Springs, CA, USA.
authors: Laura A
authors: LA
authors: Lee
authors: St. John Region, Grosse Pointe Woods, MI, USA.
authors: Carrie L
authors: CL
authors: Dul
authors: Northern Indiana Cancer Research Consortium, South Bend, IN, USA.
authors: Michael
authors: M
authors: Rotkis
authors: Breast and Melanoma Specialists of Charleston, Charleston, SC, USA.
authors: Paul
authors: P
authors: Baron
authors: Department of Medical Affairs, Agendia Inc, Irvine, CA, USA.
authors: Lisette
authors: L
authors: Stork-Sloots
authors: Department of Medical Affairs, Agendia Inc, Irvine, CA, USA.
authors: Femke A
authors: FA
authors: de Snoo
authors: The Breast Place, Charleston, SC, USA.
authors: Jennifer
authors: J
authors: Beatty
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000077384:Anastrozole; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D047072:Aromatase Inhibitors / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000145:classification* / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D001952:Bridged-Ring Compounds / Q000008:administration & dosage; D017024:Chemotherapy, Adjuvant; D000066491:Clinical Decision-Making; D003520:Cyclophosphamide / Q000008:administration & dosage; D000077143:Docetaxel; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D000077289:Letrozole; D015412:Mastectomy, Segmental; D008875:Middle Aged; D058889:Molecular Typing / Q000379:methods*; D020360:Neoadjuvant Therapy; D009570:Nitriles / Q000008:administration & dosage; D011446:Prospective Studies; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D012042:Registries; D013629:Tamoxifen / Q000008:administration & dosage; D043823:Taxoids / Q000008:administration & dosage; D016896:Treatment Outcome; D014230:Triazoles / Q000008:administration & dosage; D055815:Young Adult
chemical_list: D000077384:Anastrozole; D047072:Aromatase Inhibitors; D001952:Bridged-Ring Compounds; D003520:Cyclophosphamide; D000077143:Docetaxel; D004317:Doxorubicin; D000077289:Letrozole; D009570:Nitriles; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D013629:Tamoxifen; D043823:Taxoids; D014230:Triazoles; C080625:taxane; C508053:ERBB2 protein, human