title: Identification of key clinical phenotypes of breast cancer using a reduced panel of protein biomarkers.
abstract: BACKGROUND
  Breast cancer is a heterogeneous disease characterised by complex molecular alterations underlying the varied behaviour and response to therapy. However, translation of cancer genetic profiling for use in routine clinical practice remains elusive or prohibitively expensive. As an alternative, immunohistochemical analysis applied to routinely processed tissue samples could be used to identify distinct biological classes of breast cancer.
  
  
  METHODS
  In this study, 1073 archival breast tumours previously assessed for 25 key breast cancer biomarkers using immunohistochemistry and classified using clustering algorithms were further refined using naïve Bayes classification performance. Criteria for class membership were defined using the expression of a reduced panel of 10 proteins able to identify key molecular classes. We examined the association between these breast cancer classes with clinicopathological factors and patient outcome.
  
  
  RESULTS
  We confirm patient classification similar to established genotypic biological classes of breast cancer in addition to novel sub-divisions of luminal and basal tumours. Correlations between classes and clinicopathological parameters were in line with expectations and showed highly significant association with patient outcome. Furthermore, our novel biological class stratification provides additional prognostic information to the Nottingham Prognostic Index.
  
  
  CONCLUSIONS
  This study confirms that distinct molecular phenotypes of breast cancer can be identified using robust and routinely available techniques and both the luminal and basal breast cancer phenotypes are heterogeneous and contain distinct subgroups.
authors.affiliation: Breast Cancer Pathology Research Group, Division of Oncology, School of Medicine, Academic Unit of Clinical Oncology, University of Nottingham, Nottingham City Hospital, Hucknall Road, Nottingham NG5 1PB, UK.
authors.forename: A R
authors.initials: AR
authors.lastname: Green
authors.forename: D G
authors.initials: DG
authors.lastname: Powe
authors.forename: E A
authors.initials: EA
authors.lastname: Rakha
authors.forename: D
authors.initials: D
authors.lastname: Soria
authors.forename: C
authors.initials: C
authors.lastname: Lemetre
authors.forename: C C
authors.initials: CC
authors.lastname: Nolan
authors.forename: F F T
authors.initials: FF
authors.lastname: Barros
authors.forename: R D
authors.initials: RD
authors.lastname: Macmillan
authors.forename: J M
authors.initials: JM
authors.lastname: Garibaldi
authors.forename: G R
authors.initials: GR
authors.lastname: Ball
authors.forename: I O
authors.initials: IO
authors.lastname: Ellis
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000145:classification* / Q000235:genetics / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D009363:Neoplasm Proteins / Q000032:analysis / Q000378:metabolism*; D010641:Phenotype; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone