title: Relationship between the prognostic and predictive value of the intrinsic subtypes and a validated gene profile predictive of loco-regional control and benefit from post-mastectomy radiotherapy in patients with high-risk breast cancer.
abstract: BACKGROUND
  Breast cancer is characterized by great molecular heterogeneity demonstrated, e.g. by the intrinsic subtypes. Administration of post-mastectomy radiotherapy (PMRT) does, however, not reflect this heterogeneity. A gene profile (DBCG-RT profile) has recently been developed and validated, and has shown prognostic impact in terms of loco-regional failure and predictive impact for PMRT. Reports have also shown predictive value in terms of benefit of PMRT from intrinsic subtypes and derived approximations. The aim of this study was to examine: 1) the agreement between various methods for determining the intrinsic subtypes; and 2) the relationship between the prognostic and predictive impact of the DBCG-RT profile and the intrinsic subtypes.
  
  
  METHODS
  Intrinsic subtypes and the DBCG-RT profile was determined from microarray analysis based on fresh frozen tissue from 191 patients included in the Danish Breast Cancer Cooperative Group (DBCG) 82bc trial. Corresponding formalin-fixed, paraffin-embedded tissue was available from 146 of these patients and from another 890 DBCG82bc patients. Estrogen receptor, progesterone receptor, HER2, CK5/6, Ki-67 and EGFR were combined into immunohistochemical approximations of the intrinsic subtypes. Endpoint considered was loco-regional recurrence (LRR).
  
  
  RESULTS
  The DBCG-RT profile identified a group of patients with low risk of LRR and no additional benefit from PMRT among all subtypes. Combining six immunohistochemical markers identified a subgroup of triple negative patients with high risk of LRR and significant benefit from PMRT. Agreement in the different assignments of tumors to the subtypes was suboptimal, and the clinical outcome and predicted benefit from PMRT varied according to the method used for assignment.
  
  
  CONCLUSIONS
  The prognostic and predictive information obtained from the DBCG-RT profile cannot be substituted by any approximation of the tumors intrinsic subtype. The predictive value of the intrinsic subtypes in terms of PMRT was influenced by the method used for assignment to the intrinsic subtypes.
authors: Department of Experimental Clinical Oncology, Aarhus University Hospital , Aarhus , Denmark.
authors: Trine
authors: T
authors: Tramm
authors: Marianne
authors: M
authors: Kyndi
authors: Simen
authors: S
authors: Myhre
authors: Silje
authors: S
authors: Nord
authors: Jan
authors: J
authors: Alsner
authors: Flemming Brandt
authors: FB
authors: Sørensen
authors: Therese
authors: T
authors: Sørlie
authors: Jens
authors: J
authors: Overgaard
mesh_terms: D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology / Q000532:radiotherapy* / Q000628:therapy; D059248:Chemoradiotherapy / Q000379:methods; D003520:Cyclophosphamide / Q000008:administration & dosage; D066246:ErbB Receptors / Q000032:analysis; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D019394:Ki-67 Antigen / Q000032:analysis; D008197:Lymph Node Excision; D008408:Mastectomy; D008727:Methotrexate / Q000008:administration & dosage; D009364:Neoplasm Recurrence, Local; D011237:Predictive Value of Tests; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D013629:Tamoxifen / Q000008:administration & dosage
chemical_list: D018931:Antineoplastic Agents, Hormonal; D003520:Cyclophosphamide; D066246:ErbB Receptors; D005472:Fluorouracil; D019394:Ki-67 Antigen; D008727:Methotrexate; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D013629:Tamoxifen