title: Defining breast cancer intrinsic subtypes by quantitative receptor expression.
abstract: OBJECTIVE
  To determine intrinsic breast cancer subtypes represented within categories defined by quantitative hormone receptor (HR) and HER2 expression.
  
  
  METHODS
  We merged 1,557 cases from three randomized phase III trials into a single data set. These breast tumors were centrally reviewed in each trial for quantitative ER, PR, and HER2 expression by immunohistochemistry (IHC) stain and by reverse transcription-quantitative polymerase chain reaction (RT-qPCR), with intrinsic subtyping by research-based PAM50 RT-qPCR assay.
  
  
  RESULTS
  Among 283 HER2-negative tumors with <1% HR expression by IHC, 207 (73%) were basal-like; other subtypes, particularly HER2-enriched (48, 17%), were present. Among the 1,298 HER2-negative tumors, borderline HR (1%-9% staining) was uncommon (n = 39), and these tumors were heterogeneous: 17 (44%) luminal A/B, 12 (31%) HER2-enriched, and only 7 (18%) basal-like. Including them in the definition of triple-negative breast cancer significantly diminished enrichment for basal-like cancer (p < .05). Among 106 HER2-positive tumors with <1% HR expression by IHC, the HER2-enriched subtype was the most frequent (87, 82%), whereas among 127 HER2-positive tumors with strong HR (>10%) expression, only 69 (54%) were HER2-enriched and 55 (43%) were luminal (39 luminal B, 16 luminal A). Quantitative HR expression by RT-qPCR gave similar results. Regardless of methodology, basal-like cases seldom expressed ER/ESR1 or PR/PGR and were associated with the lowest expression level of HER2/ERBB2 relative to other subtypes.
  
  
  CONCLUSIONS
  Significant discordance remains between clinical assay-defined subsets and intrinsic subtype. For identifying basal-like breast cancer, the optimal HR IHC cut point was <1%, matching the American Society of Clinical Oncology and College of American Pathologists guidelines. Tumors with borderline HR staining are molecularly diverse and may require additional assays to clarify underlying biology.
authors.affiliation: Lineberger Comprehensive Cancer Center and Department of Genetics, University of North Carolina, Chapel Hill, North Carolina, USA; Clinical Trials and Statistics Unit at The Institute of Cancer Research, London, United Kingdom; Servicio de Oncología Médica, Instituto de Investigacion Sanitaria Hospital Universitario Gregorio Marañón, Facultad de Medicina, Universidad Complutense, Madrid, Spain; Department of Pathology, University of British Columbia, Vancouver, British Columbia, Canada; Translation Genomics Unit, Vall d´Hebron Institute of Oncology, Barcelona, Spain; British Columbia Cancer Agency, Vancouver, British Columbia, Canada; Department of Medical Oncology, Hospital General Universitario de Elche, Alicante, Spain; Department of Medical Oncology, Instituto Valenciano de Oncologia, Valencia, Spain; National Cancer Institute of Canada Clinical Trials Group, Kingston, Ontario, Canada; Department of Medical Oncology, Hospital Universitario Virgen del Rocio, Seville, Spain; Department of Medical Oncology, Complejo Hospitalario Universitario A Coruña, Coruña, Spain; Department of Medical Oncology, Hospital Universitario Virgen de la Victoria, Málaga, Spain; GEICAM, Madrid, Spain; Sunnybrook Odette Cancer Centre, University of Toronto, Toronto, Ontario, Canada; McMaster University, Hamilton, Ontario, Canada; Department of Oncology, Tom Baker Cancer Centre, University of Calgary, Calgary, Alberta, Canada; Department of Pathology, University of Utah Health Sciences Center, Salt Lake City, Utah, USA; Department of Medicine, Washington University, St. Louis, Missouri, USA; Department of Oncology, Hospital of Prato, Istituto Toscani Tumori, Florence, Italy.
authors.forename: Maggie C U
authors.initials: MC
authors.lastname: Cheang
authors.affiliation: Lineberger Comprehensive Cancer Center and Department of Genetics, University of North Carolina, Chapel Hill, North Carolina, USA; Clinical Trials and Statistics Unit at The Institute of Cancer Research, London, United Kingdom; Servicio de Oncología Médica, Instituto de Investigacion Sanitaria Hospital Universitario Gregorio Marañón, Facultad de Medicina, Universidad Complutense, Madrid, Spain; Department of Pathology, University of British Columbia, Vancouver, British Columbia, Canada; Translation Genomics Unit, Vall d´Hebron Institute of Oncology, Barcelona, Spain; British Columbia Cancer Agency, Vancouver, British Columbia, Canada; Department of Medical Oncology, Hospital General Universitario de Elche, Alicante, Spain; Department of Medical Oncology, Instituto Valenciano de Oncologia, Valencia, Spain; National Cancer Institute of Canada Clinical Trials Group, Kingston, Ontario, Canada; Department of Medical Oncology, Hospital Universitario Virgen del Rocio, Seville, Spain; Department of Medical Oncology, Complejo Hospitalario Universitario A Coruña, Coruña, Spain; Department of Medical Oncology, Hospital Universitario Virgen de la Victoria, Málaga, Spain; GEICAM, Madrid, Spain; Sunnybrook Odette Cancer Centre, University of Toronto, Toronto, Ontario, Canada; McMaster University, Hamilton, Ontario, Canada; Department of Oncology, Tom Baker Cancer Centre, University of Calgary, Calgary, Alberta, Canada; Department of Pathology, University of Utah Health Sciences Center, Salt Lake City, Utah, USA; Department of Medicine, Washington University, St. Louis, Missouri, USA; Department of Oncology, Hospital of Prato, Istituto Toscani Tumori, Florence, Italy.
authors.forename: Miguel
authors.initials: M
authors.lastname: Martin
authors.affiliation: Lineberger Comprehensive Cancer Center and Department of Genetics, University of North Carolina, Chapel Hill, North Carolina, USA; Clinical Trials and Statistics Unit at The Institute of Cancer Research, London, United Kingdom; Servicio de Oncología Médica, Instituto de Investigacion Sanitaria Hospital Universitario Gregorio Marañón, Facultad de Medicina, Universidad Complutense, Madrid, Spain; Department of Pathology, University of British Columbia, Vancouver, British Columbia, Canada; Translation Genomics Unit, Vall d´Hebron Institute of Oncology, Barcelona, Spain; British Columbia Cancer Agency, Vancouver, British Columbia, Canada; Department of Medical Oncology, Hospital General Universitario de Elche, Alicante, Spain; Department of Medical Oncology, Instituto Valenciano de Oncologia, Valencia, Spain; National Cancer Institute of Canada Clinical Trials Group, Kingston, Ontario, Canada; Department of Medical Oncology, Hospital Universitario Virgen del Rocio, Seville, Spain; Department of Medical Oncology, Complejo Hospitalario Universitario A Coruña, Coruña, Spain; Department of Medical Oncology, Hospital Universitario Virgen de la Victoria, Málaga, Spain; GEICAM, Madrid, Spain; Sunnybrook Odette Cancer Centre, University of Toronto, Toronto, Ontario, Canada; McMaster University, Hamilton, Ontario, Canada; Department of Oncology, Tom Baker Cancer Centre, University of Calgary, Calgary, Alberta, Canada; Department of Pathology, University of Utah Health Sciences Center, Salt Lake City, Utah, USA; Department of Medicine, Washington University, St. Louis, Missouri, USA; Department of Oncology, Hospital of Prato, Istituto Toscani Tumori, Florence, Italy.
authors.forename: Torsten O
authors.initials: TO
authors.lastname: Nielsen
authors.affiliation: Lineberger Comprehensive Cancer Center and Department of Genetics, University of North Carolina, Chapel Hill, North Carolina, USA; Clinical Trials and Statistics Unit at The Institute of Cancer Research, London, United Kingdom; Servicio de Oncología Médica, Instituto de Investigacion Sanitaria Hospital Universitario Gregorio Marañón, Facultad de Medicina, Universidad Complutense, Madrid, Spain; Department of Pathology, University of British Columbia, Vancouver, British Columbia, Canada; Translation Genomics Unit, Vall d´Hebron Institute of Oncology, Barcelona, Spain; British Columbia Cancer Agency, Vancouver, British Columbia, Canada; Department of Medical Oncology, Hospital General Universitario de Elche, Alicante, Spain; Department of Medical Oncology, Instituto Valenciano de Oncologia, Valencia, Spain; National Cancer Institute of Canada Clinical Trials Group, Kingston, Ontario, Canada; Department of Medical Oncology, Hospital Universitario Virgen del Rocio, Seville, Spain; Department of Medical Oncology, Complejo Hospitalario Universitario A Coruña, Coruña, Spain; Department of Medical Oncology, Hospital Universitario Virgen de la Victoria, Málaga, Spain; GEICAM, Madrid, Spain; Sunnybrook Odette Cancer Centre, University of Toronto, Toronto, Ontario, Canada; McMaster University, Hamilton, Ontario, Canada; Department of Oncology, Tom Baker Cancer Centre, University of Calgary, Calgary, Alberta, Canada; Department of Pathology, University of Utah Health Sciences Center, Salt Lake City, Utah, USA; Department of Medicine, Washington University, St. Louis, Missouri, USA; Department of Oncology, Hospital of Prato, Istituto Toscani Tumori, Florence, Italy.
authors.forename: Aleix
authors.initials: A
authors.lastname: Prat
authors.affiliation: Lineberger Comprehensive Cancer Center and Department of Genetics, University of North Carolina, Chapel Hill, North Carolina, USA; Clinical Trials and Statistics Unit at The Institute of Cancer Research, London, United Kingdom; Servicio de Oncología Médica, Instituto de Investigacion Sanitaria Hospital Universitario Gregorio Marañón, Facultad de Medicina, Universidad Complutense, Madrid, Spain; Department of Pathology, University of British Columbia, Vancouver, British Columbia, Canada; Translation Genomics Unit, Vall d´Hebron Institute of Oncology, Barcelona, Spain; British Columbia Cancer Agency, Vancouver, British Columbia, Canada; Department of Medical Oncology, Hospital General Universitario de Elche, Alicante, Spain; Department of Medical Oncology, Instituto Valenciano de Oncologia, Valencia, Spain; National Cancer Institute of Canada Clinical Trials Group, Kingston, Ontario, Canada; Department of Medical Oncology, Hospital Universitario Virgen del Rocio, Seville, Spain; Department of Medical Oncology, Complejo Hospitalario Universitario A Coruña, Coruña, Spain; Department of Medical Oncology, Hospital Universitario Virgen de la Victoria, Málaga, Spain; GEICAM, Madrid, Spain; Sunnybrook Odette Cancer Centre, University of Toronto, Toronto, Ontario, Canada; McMaster University, Hamilton, Ontario, Canada; Department of Oncology, Tom Baker Cancer Centre, University of Calgary, Calgary, Alberta, Canada; Department of Pathology, University of Utah Health Sciences Center, Salt Lake City, Utah, USA; Department of Medicine, Washington University, St. Louis, Missouri, USA; Department of Oncology, Hospital of Prato, Istituto Toscani Tumori, Florence, Italy.
authors.forename: David
authors.initials: D
authors.lastname: Voduc
authors.affiliation: Lineberger Comprehensive Cancer Center and Department of Genetics, University of North Carolina, Chapel Hill, North Carolina, USA; Clinical Trials and Statistics Unit at The Institute of Cancer Research, London, United Kingdom; Servicio de Oncología Médica, Instituto de Investigacion Sanitaria Hospital Universitario Gregorio Marañón, Facultad de Medicina, Universidad Complutense, Madrid, Spain; Department of Pathology, University of British Columbia, Vancouver, British Columbia, Canada; Translation Genomics Unit, Vall d´Hebron Institute of Oncology, Barcelona, Spain; British Columbia Cancer Agency, Vancouver, British Columbia, Canada; Department of Medical Oncology, Hospital General Universitario de Elche, Alicante, Spain; Department of Medical Oncology, Instituto Valenciano de Oncologia, Valencia, Spain; National Cancer Institute of Canada Clinical Trials Group, Kingston, Ontario, Canada; Department of Medical Oncology, Hospital Universitario Virgen del Rocio, Seville, Spain; Department of Medical Oncology, Complejo Hospitalario Universitario A Coruña, Coruña, Spain; Department of Medical Oncology, Hospital Universitario Virgen de la Victoria, Málaga, Spain; GEICAM, Madrid, Spain; Sunnybrook Odette Cancer Centre, University of Toronto, Toronto, Ontario, Canada; McMaster University, Hamilton, Ontario, Canada; Department of Oncology, Tom Baker Cancer Centre, University of Calgary, Calgary, Alberta, Canada; Department of Pathology, University of Utah Health Sciences Center, Salt Lake City, Utah, USA; Department of Medicine, Washington University, St. Louis, Missouri, USA; Department of Oncology, Hospital of Prato, Istituto Toscani Tumori, Florence, Italy.
authors.forename: Alvaro
authors.initials: A
authors.lastname: Rodriguez-Lescure
authors.affiliation: Lineberger Comprehensive Cancer Center and Department of Genetics, University of North Carolina, Chapel Hill, North Carolina, USA; Clinical Trials and Statistics Unit at The Institute of Cancer Research, London, United Kingdom; Servicio de Oncología Médica, Instituto de Investigacion Sanitaria Hospital Universitario Gregorio Marañón, Facultad de Medicina, Universidad Complutense, Madrid, Spain; Department of Pathology, University of British Columbia, Vancouver, British Columbia, Canada; Translation Genomics Unit, Vall d´Hebron Institute of Oncology, Barcelona, Spain; British Columbia Cancer Agency, Vancouver, British Columbia, Canada; Department of Medical Oncology, Hospital General Universitario de Elche, Alicante, Spain; Department of Medical Oncology, Instituto Valenciano de Oncologia, Valencia, Spain; National Cancer Institute of Canada Clinical Trials Group, Kingston, Ontario, Canada; Department of Medical Oncology, Hospital Universitario Virgen del Rocio, Seville, Spain; Department of Medical Oncology, Complejo Hospitalario Universitario A Coruña, Coruña, Spain; Department of Medical Oncology, Hospital Universitario Virgen de la Victoria, Málaga, Spain; GEICAM, Madrid, Spain; Sunnybrook Odette Cancer Centre, University of Toronto, Toronto, Ontario, Canada; McMaster University, Hamilton, Ontario, Canada; Department of Oncology, Tom Baker Cancer Centre, University of Calgary, Calgary, Alberta, Canada; Department of Pathology, University of Utah Health Sciences Center, Salt Lake City, Utah, USA; Department of Medicine, Washington University, St. Louis, Missouri, USA; Department of Oncology, Hospital of Prato, Istituto Toscani Tumori, Florence, Italy.
authors.forename: Amparo
authors.initials: A
authors.lastname: Ruiz
authors.affiliation: Lineberger Comprehensive Cancer Center and Department of Genetics, University of North Carolina, Chapel Hill, North Carolina, USA; Clinical Trials and Statistics Unit at The Institute of Cancer Research, London, United Kingdom; Servicio de Oncología Médica, Instituto de Investigacion Sanitaria Hospital Universitario Gregorio Marañón, Facultad de Medicina, Universidad Complutense, Madrid, Spain; Department of Pathology, University of British Columbia, Vancouver, British Columbia, Canada; Translation Genomics Unit, Vall d´Hebron Institute of Oncology, Barcelona, Spain; British Columbia Cancer Agency, Vancouver, British Columbia, Canada; Department of Medical Oncology, Hospital General Universitario de Elche, Alicante, Spain; Department of Medical Oncology, Instituto Valenciano de Oncologia, Valencia, Spain; National Cancer Institute of Canada Clinical Trials Group, Kingston, Ontario, Canada; Department of Medical Oncology, Hospital Universitario Virgen del Rocio, Seville, Spain; Department of Medical Oncology, Complejo Hospitalario Universitario A Coruña, Coruña, Spain; Department of Medical Oncology, Hospital Universitario Virgen de la Victoria, Málaga, Spain; GEICAM, Madrid, Spain; Sunnybrook Odette Cancer Centre, University of Toronto, Toronto, Ontario, Canada; McMaster University, Hamilton, Ontario, Canada; Department of Oncology, Tom Baker Cancer Centre, University of Calgary, Calgary, Alberta, Canada; Department of Pathology, University of Utah Health Sciences Center, Salt Lake City, Utah, USA; Department of Medicine, Washington University, St. Louis, Missouri, USA; Department of Oncology, Hospital of Prato, Istituto Toscani Tumori, Florence, Italy.
authors.forename: Stephen
authors.initials: S
authors.lastname: Chia
authors.affiliation: Lineberger Comprehensive Cancer Center and Department of Genetics, University of North Carolina, Chapel Hill, North Carolina, USA; Clinical Trials and Statistics Unit at The Institute of Cancer Research, London, United Kingdom; Servicio de Oncología Médica, Instituto de Investigacion Sanitaria Hospital Universitario Gregorio Marañón, Facultad de Medicina, Universidad Complutense, Madrid, Spain; Department of Pathology, University of British Columbia, Vancouver, British Columbia, Canada; Translation Genomics Unit, Vall d´Hebron Institute of Oncology, Barcelona, Spain; British Columbia Cancer Agency, Vancouver, British Columbia, Canada; Department of Medical Oncology, Hospital General Universitario de Elche, Alicante, Spain; Department of Medical Oncology, Instituto Valenciano de Oncologia, Valencia, Spain; National Cancer Institute of Canada Clinical Trials Group, Kingston, Ontario, Canada; Department of Medical Oncology, Hospital Universitario Virgen del Rocio, Seville, Spain; Department of Medical Oncology, Complejo Hospitalario Universitario A Coruña, Coruña, Spain; Department of Medical Oncology, Hospital Universitario Virgen de la Victoria, Málaga, Spain; GEICAM, Madrid, Spain; Sunnybrook Odette Cancer Centre, University of Toronto, Toronto, Ontario, Canada; McMaster University, Hamilton, Ontario, Canada; Department of Oncology, Tom Baker Cancer Centre, University of Calgary, Calgary, Alberta, Canada; Department of Pathology, University of Utah Health Sciences Center, Salt Lake City, Utah, USA; Department of Medicine, Washington University, St. Louis, Missouri, USA; Department of Oncology, Hospital of Prato, Istituto Toscani Tumori, Florence, Italy.
authors.forename: Lois
authors.initials: L
authors.lastname: Shepherd
authors.affiliation: Lineberger Comprehensive Cancer Center and Department of Genetics, University of North Carolina, Chapel Hill, North Carolina, USA; Clinical Trials and Statistics Unit at The Institute of Cancer Research, London, United Kingdom; Servicio de Oncología Médica, Instituto de Investigacion Sanitaria Hospital Universitario Gregorio Marañón, Facultad de Medicina, Universidad Complutense, Madrid, Spain; Department of Pathology, University of British Columbia, Vancouver, British Columbia, Canada; Translation Genomics Unit, Vall d´Hebron Institute of Oncology, Barcelona, Spain; British Columbia Cancer Agency, Vancouver, British Columbia, Canada; Department of Medical Oncology, Hospital General Universitario de Elche, Alicante, Spain; Department of Medical Oncology, Instituto Valenciano de Oncologia, Valencia, Spain; National Cancer Institute of Canada Clinical Trials Group, Kingston, Ontario, Canada; Department of Medical Oncology, Hospital Universitario Virgen del Rocio, Seville, Spain; Department of Medical Oncology, Complejo Hospitalario Universitario A Coruña, Coruña, Spain; Department of Medical Oncology, Hospital Universitario Virgen de la Victoria, Málaga, Spain; GEICAM, Madrid, Spain; Sunnybrook Odette Cancer Centre, University of Toronto, Toronto, Ontario, Canada; McMaster University, Hamilton, Ontario, Canada; Department of Oncology, Tom Baker Cancer Centre, University of Calgary, Calgary, Alberta, Canada; Department of Pathology, University of Utah Health Sciences Center, Salt Lake City, Utah, USA; Department of Medicine, Washington University, St. Louis, Missouri, USA; Department of Oncology, Hospital of Prato, Istituto Toscani Tumori, Florence, Italy.
authors.forename: Manuel
authors.initials: M
authors.lastname: Ruiz-Borrego
authors.affiliation: Lineberger Comprehensive Cancer Center and Department of Genetics, University of North Carolina, Chapel Hill, North Carolina, USA; Clinical Trials and Statistics Unit at The Institute of Cancer Research, London, United Kingdom; Servicio de Oncología Médica, Instituto de Investigacion Sanitaria Hospital Universitario Gregorio Marañón, Facultad de Medicina, Universidad Complutense, Madrid, Spain; Department of Pathology, University of British Columbia, Vancouver, British Columbia, Canada; Translation Genomics Unit, Vall d´Hebron Institute of Oncology, Barcelona, Spain; British Columbia Cancer Agency, Vancouver, British Columbia, Canada; Department of Medical Oncology, Hospital General Universitario de Elche, Alicante, Spain; Department of Medical Oncology, Instituto Valenciano de Oncologia, Valencia, Spain; National Cancer Institute of Canada Clinical Trials Group, Kingston, Ontario, Canada; Department of Medical Oncology, Hospital Universitario Virgen del Rocio, Seville, Spain; Department of Medical Oncology, Complejo Hospitalario Universitario A Coruña, Coruña, Spain; Department of Medical Oncology, Hospital Universitario Virgen de la Victoria, Málaga, Spain; GEICAM, Madrid, Spain; Sunnybrook Odette Cancer Centre, University of Toronto, Toronto, Ontario, Canada; McMaster University, Hamilton, Ontario, Canada; Department of Oncology, Tom Baker Cancer Centre, University of Calgary, Calgary, Alberta, Canada; Department of Pathology, University of Utah Health Sciences Center, Salt Lake City, Utah, USA; Department of Medicine, Washington University, St. Louis, Missouri, USA; Department of Oncology, Hospital of Prato, Istituto Toscani Tumori, Florence, Italy.
authors.forename: Lourdes
authors.initials: L
authors.lastname: Calvo
authors.affiliation: Lineberger Comprehensive Cancer Center and Department of Genetics, University of North Carolina, Chapel Hill, North Carolina, USA; Clinical Trials and Statistics Unit at The Institute of Cancer Research, London, United Kingdom; Servicio de Oncología Médica, Instituto de Investigacion Sanitaria Hospital Universitario Gregorio Marañón, Facultad de Medicina, Universidad Complutense, Madrid, Spain; Department of Pathology, University of British Columbia, Vancouver, British Columbia, Canada; Translation Genomics Unit, Vall d´Hebron Institute of Oncology, Barcelona, Spain; British Columbia Cancer Agency, Vancouver, British Columbia, Canada; Department of Medical Oncology, Hospital General Universitario de Elche, Alicante, Spain; Department of Medical Oncology, Instituto Valenciano de Oncologia, Valencia, Spain; National Cancer Institute of Canada Clinical Trials Group, Kingston, Ontario, Canada; Department of Medical Oncology, Hospital Universitario Virgen del Rocio, Seville, Spain; Department of Medical Oncology, Complejo Hospitalario Universitario A Coruña, Coruña, Spain; Department of Medical Oncology, Hospital Universitario Virgen de la Victoria, Málaga, Spain; GEICAM, Madrid, Spain; Sunnybrook Odette Cancer Centre, University of Toronto, Toronto, Ontario, Canada; McMaster University, Hamilton, Ontario, Canada; Department of Oncology, Tom Baker Cancer Centre, University of Calgary, Calgary, Alberta, Canada; Department of Pathology, University of Utah Health Sciences Center, Salt Lake City, Utah, USA; Department of Medicine, Washington University, St. Louis, Missouri, USA; Department of Oncology, Hospital of Prato, Istituto Toscani Tumori, Florence, Italy.
authors.forename: Emilio
authors.initials: E
authors.lastname: Alba
authors.affiliation: Lineberger Comprehensive Cancer Center and Department of Genetics, University of North Carolina, Chapel Hill, North Carolina, USA; Clinical Trials and Statistics Unit at The Institute of Cancer Research, London, United Kingdom; Servicio de Oncología Médica, Instituto de Investigacion Sanitaria Hospital Universitario Gregorio Marañón, Facultad de Medicina, Universidad Complutense, Madrid, Spain; Department of Pathology, University of British Columbia, Vancouver, British Columbia, Canada; Translation Genomics Unit, Vall d´Hebron Institute of Oncology, Barcelona, Spain; British Columbia Cancer Agency, Vancouver, British Columbia, Canada; Department of Medical Oncology, Hospital General Universitario de Elche, Alicante, Spain; Department of Medical Oncology, Instituto Valenciano de Oncologia, Valencia, Spain; National Cancer Institute of Canada Clinical Trials Group, Kingston, Ontario, Canada; Department of Medical Oncology, Hospital Universitario Virgen del Rocio, Seville, Spain; Department of Medical Oncology, Complejo Hospitalario Universitario A Coruña, Coruña, Spain; Department of Medical Oncology, Hospital Universitario Virgen de la Victoria, Málaga, Spain; GEICAM, Madrid, Spain; Sunnybrook Odette Cancer Centre, University of Toronto, Toronto, Ontario, Canada; McMaster University, Hamilton, Ontario, Canada; Department of Oncology, Tom Baker Cancer Centre, University of Calgary, Calgary, Alberta, Canada; Department of Pathology, University of Utah Health Sciences Center, Salt Lake City, Utah, USA; Department of Medicine, Washington University, St. Louis, Missouri, USA; Department of Oncology, Hospital of Prato, Istituto Toscani Tumori, Florence, Italy.
authors.forename: Eva
authors.initials: E
authors.lastname: Carrasco
authors.affiliation: Lineberger Comprehensive Cancer Center and Department of Genetics, University of North Carolina, Chapel Hill, North Carolina, USA; Clinical Trials and Statistics Unit at The Institute of Cancer Research, London, United Kingdom; Servicio de Oncología Médica, Instituto de Investigacion Sanitaria Hospital Universitario Gregorio Marañón, Facultad de Medicina, Universidad Complutense, Madrid, Spain; Department of Pathology, University of British Columbia, Vancouver, British Columbia, Canada; Translation Genomics Unit, Vall d´Hebron Institute of Oncology, Barcelona, Spain; British Columbia Cancer Agency, Vancouver, British Columbia, Canada; Department of Medical Oncology, Hospital General Universitario de Elche, Alicante, Spain; Department of Medical Oncology, Instituto Valenciano de Oncologia, Valencia, Spain; National Cancer Institute of Canada Clinical Trials Group, Kingston, Ontario, Canada; Department of Medical Oncology, Hospital Universitario Virgen del Rocio, Seville, Spain; Department of Medical Oncology, Complejo Hospitalario Universitario A Coruña, Coruña, Spain; Department of Medical Oncology, Hospital Universitario Virgen de la Victoria, Málaga, Spain; GEICAM, Madrid, Spain; Sunnybrook Odette Cancer Centre, University of Toronto, Toronto, Ontario, Canada; McMaster University, Hamilton, Ontario, Canada; Department of Oncology, Tom Baker Cancer Centre, University of Calgary, Calgary, Alberta, Canada; Department of Pathology, University of Utah Health Sciences Center, Salt Lake City, Utah, USA; Department of Medicine, Washington University, St. Louis, Missouri, USA; Department of Oncology, Hospital of Prato, Istituto Toscani Tumori, Florence, Italy.
authors.forename: Rosalia
authors.initials: R
authors.lastname: Caballero
authors.affiliation: Lineberger Comprehensive Cancer Center and Department of Genetics, University of North Carolina, Chapel Hill, North Carolina, USA; Clinical Trials and Statistics Unit at The Institute of Cancer Research, London, United Kingdom; Servicio de Oncología Médica, Instituto de Investigacion Sanitaria Hospital Universitario Gregorio Marañón, Facultad de Medicina, Universidad Complutense, Madrid, Spain; Department of Pathology, University of British Columbia, Vancouver, British Columbia, Canada; Translation Genomics Unit, Vall d´Hebron Institute of Oncology, Barcelona, Spain; British Columbia Cancer Agency, Vancouver, British Columbia, Canada; Department of Medical Oncology, Hospital General Universitario de Elche, Alicante, Spain; Department of Medical Oncology, Instituto Valenciano de Oncologia, Valencia, Spain; National Cancer Institute of Canada Clinical Trials Group, Kingston, Ontario, Canada; Department of Medical Oncology, Hospital Universitario Virgen del Rocio, Seville, Spain; Department of Medical Oncology, Complejo Hospitalario Universitario A Coruña, Coruña, Spain; Department of Medical Oncology, Hospital Universitario Virgen de la Victoria, Málaga, Spain; GEICAM, Madrid, Spain; Sunnybrook Odette Cancer Centre, University of Toronto, Toronto, Ontario, Canada; McMaster University, Hamilton, Ontario, Canada; Department of Oncology, Tom Baker Cancer Centre, University of Calgary, Calgary, Alberta, Canada; Department of Pathology, University of Utah Health Sciences Center, Salt Lake City, Utah, USA; Department of Medicine, Washington University, St. Louis, Missouri, USA; Department of Oncology, Hospital of Prato, Istituto Toscani Tumori, Florence, Italy.
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Tu
authors.affiliation: Lineberger Comprehensive Cancer Center and Department of Genetics, University of North Carolina, Chapel Hill, North Carolina, USA; Clinical Trials and Statistics Unit at The Institute of Cancer Research, London, United Kingdom; Servicio de Oncología Médica, Instituto de Investigacion Sanitaria Hospital Universitario Gregorio Marañón, Facultad de Medicina, Universidad Complutense, Madrid, Spain; Department of Pathology, University of British Columbia, Vancouver, British Columbia, Canada; Translation Genomics Unit, Vall d´Hebron Institute of Oncology, Barcelona, Spain; British Columbia Cancer Agency, Vancouver, British Columbia, Canada; Department of Medical Oncology, Hospital General Universitario de Elche, Alicante, Spain; Department of Medical Oncology, Instituto Valenciano de Oncologia, Valencia, Spain; National Cancer Institute of Canada Clinical Trials Group, Kingston, Ontario, Canada; Department of Medical Oncology, Hospital Universitario Virgen del Rocio, Seville, Spain; Department of Medical Oncology, Complejo Hospitalario Universitario A Coruña, Coruña, Spain; Department of Medical Oncology, Hospital Universitario Virgen de la Victoria, Málaga, Spain; GEICAM, Madrid, Spain; Sunnybrook Odette Cancer Centre, University of Toronto, Toronto, Ontario, Canada; McMaster University, Hamilton, Ontario, Canada; Department of Oncology, Tom Baker Cancer Centre, University of Calgary, Calgary, Alberta, Canada; Department of Pathology, University of Utah Health Sciences Center, Salt Lake City, Utah, USA; Department of Medicine, Washington University, St. Louis, Missouri, USA; Department of Oncology, Hospital of Prato, Istituto Toscani Tumori, Florence, Italy.
authors.forename: Kathleen I
authors.initials: KI
authors.lastname: Pritchard
authors.affiliation: Lineberger Comprehensive Cancer Center and Department of Genetics, University of North Carolina, Chapel Hill, North Carolina, USA; Clinical Trials and Statistics Unit at The Institute of Cancer Research, London, United Kingdom; Servicio de Oncología Médica, Instituto de Investigacion Sanitaria Hospital Universitario Gregorio Marañón, Facultad de Medicina, Universidad Complutense, Madrid, Spain; Department of Pathology, University of British Columbia, Vancouver, British Columbia, Canada; Translation Genomics Unit, Vall d´Hebron Institute of Oncology, Barcelona, Spain; British Columbia Cancer Agency, Vancouver, British Columbia, Canada; Department of Medical Oncology, Hospital General Universitario de Elche, Alicante, Spain; Department of Medical Oncology, Instituto Valenciano de Oncologia, Valencia, Spain; National Cancer Institute of Canada Clinical Trials Group, Kingston, Ontario, Canada; Department of Medical Oncology, Hospital Universitario Virgen del Rocio, Seville, Spain; Department of Medical Oncology, Complejo Hospitalario Universitario A Coruña, Coruña, Spain; Department of Medical Oncology, Hospital Universitario Virgen de la Victoria, Málaga, Spain; GEICAM, Madrid, Spain; Sunnybrook Odette Cancer Centre, University of Toronto, Toronto, Ontario, Canada; McMaster University, Hamilton, Ontario, Canada; Department of Oncology, Tom Baker Cancer Centre, University of Calgary, Calgary, Alberta, Canada; Department of Pathology, University of Utah Health Sciences Center, Salt Lake City, Utah, USA; Department of Medicine, Washington University, St. Louis, Missouri, USA; Department of Oncology, Hospital of Prato, Istituto Toscani Tumori, Florence, Italy.
authors.forename: Mark N
authors.initials: MN
authors.lastname: Levine
authors.affiliation: Lineberger Comprehensive Cancer Center and Department of Genetics, University of North Carolina, Chapel Hill, North Carolina, USA; Clinical Trials and Statistics Unit at The Institute of Cancer Research, London, United Kingdom; Servicio de Oncología Médica, Instituto de Investigacion Sanitaria Hospital Universitario Gregorio Marañón, Facultad de Medicina, Universidad Complutense, Madrid, Spain; Department of Pathology, University of British Columbia, Vancouver, British Columbia, Canada; Translation Genomics Unit, Vall d´Hebron Institute of Oncology, Barcelona, Spain; British Columbia Cancer Agency, Vancouver, British Columbia, Canada; Department of Medical Oncology, Hospital General Universitario de Elche, Alicante, Spain; Department of Medical Oncology, Instituto Valenciano de Oncologia, Valencia, Spain; National Cancer Institute of Canada Clinical Trials Group, Kingston, Ontario, Canada; Department of Medical Oncology, Hospital Universitario Virgen del Rocio, Seville, Spain; Department of Medical Oncology, Complejo Hospitalario Universitario A Coruña, Coruña, Spain; Department of Medical Oncology, Hospital Universitario Virgen de la Victoria, Málaga, Spain; GEICAM, Madrid, Spain; Sunnybrook Odette Cancer Centre, University of Toronto, Toronto, Ontario, Canada; McMaster University, Hamilton, Ontario, Canada; Department of Oncology, Tom Baker Cancer Centre, University of Calgary, Calgary, Alberta, Canada; Department of Pathology, University of Utah Health Sciences Center, Salt Lake City, Utah, USA; Department of Medicine, Washington University, St. Louis, Missouri, USA; Department of Oncology, Hospital of Prato, Istituto Toscani Tumori, Florence, Italy.
authors.forename: Vivien H
authors.initials: VH
authors.lastname: Bramwell
authors.affiliation: Lineberger Comprehensive Cancer Center and Department of Genetics, University of North Carolina, Chapel Hill, North Carolina, USA; Clinical Trials and Statistics Unit at The Institute of Cancer Research, London, United Kingdom; Servicio de Oncología Médica, Instituto de Investigacion Sanitaria Hospital Universitario Gregorio Marañón, Facultad de Medicina, Universidad Complutense, Madrid, Spain; Department of Pathology, University of British Columbia, Vancouver, British Columbia, Canada; Translation Genomics Unit, Vall d´Hebron Institute of Oncology, Barcelona, Spain; British Columbia Cancer Agency, Vancouver, British Columbia, Canada; Department of Medical Oncology, Hospital General Universitario de Elche, Alicante, Spain; Department of Medical Oncology, Instituto Valenciano de Oncologia, Valencia, Spain; National Cancer Institute of Canada Clinical Trials Group, Kingston, Ontario, Canada; Department of Medical Oncology, Hospital Universitario Virgen del Rocio, Seville, Spain; Department of Medical Oncology, Complejo Hospitalario Universitario A Coruña, Coruña, Spain; Department of Medical Oncology, Hospital Universitario Virgen de la Victoria, Málaga, Spain; GEICAM, Madrid, Spain; Sunnybrook Odette Cancer Centre, University of Toronto, Toronto, Ontario, Canada; McMaster University, Hamilton, Ontario, Canada; Department of Oncology, Tom Baker Cancer Centre, University of Calgary, Calgary, Alberta, Canada; Department of Pathology, University of Utah Health Sciences Center, Salt Lake City, Utah, USA; Department of Medicine, Washington University, St. Louis, Missouri, USA; Department of Oncology, Hospital of Prato, Istituto Toscani Tumori, Florence, Italy.
authors.forename: Joel
authors.initials: J
authors.lastname: Parker
authors.affiliation: Lineberger Comprehensive Cancer Center and Department of Genetics, University of North Carolina, Chapel Hill, North Carolina, USA; Clinical Trials and Statistics Unit at The Institute of Cancer Research, London, United Kingdom; Servicio de Oncología Médica, Instituto de Investigacion Sanitaria Hospital Universitario Gregorio Marañón, Facultad de Medicina, Universidad Complutense, Madrid, Spain; Department of Pathology, University of British Columbia, Vancouver, British Columbia, Canada; Translation Genomics Unit, Vall d´Hebron Institute of Oncology, Barcelona, Spain; British Columbia Cancer Agency, Vancouver, British Columbia, Canada; Department of Medical Oncology, Hospital General Universitario de Elche, Alicante, Spain; Department of Medical Oncology, Instituto Valenciano de Oncologia, Valencia, Spain; National Cancer Institute of Canada Clinical Trials Group, Kingston, Ontario, Canada; Department of Medical Oncology, Hospital Universitario Virgen del Rocio, Seville, Spain; Department of Medical Oncology, Complejo Hospitalario Universitario A Coruña, Coruña, Spain; Department of Medical Oncology, Hospital Universitario Virgen de la Victoria, Málaga, Spain; GEICAM, Madrid, Spain; Sunnybrook Odette Cancer Centre, University of Toronto, Toronto, Ontario, Canada; McMaster University, Hamilton, Ontario, Canada; Department of Oncology, Tom Baker Cancer Centre, University of Calgary, Calgary, Alberta, Canada; Department of Pathology, University of Utah Health Sciences Center, Salt Lake City, Utah, USA; Department of Medicine, Washington University, St. Louis, Missouri, USA; Department of Oncology, Hospital of Prato, Istituto Toscani Tumori, Florence, Italy.
authors.forename: Philip S
authors.initials: PS
authors.lastname: Bernard
authors.affiliation: Lineberger Comprehensive Cancer Center and Department of Genetics, University of North Carolina, Chapel Hill, North Carolina, USA; Clinical Trials and Statistics Unit at The Institute of Cancer Research, London, United Kingdom; Servicio de Oncología Médica, Instituto de Investigacion Sanitaria Hospital Universitario Gregorio Marañón, Facultad de Medicina, Universidad Complutense, Madrid, Spain; Department of Pathology, University of British Columbia, Vancouver, British Columbia, Canada; Translation Genomics Unit, Vall d´Hebron Institute of Oncology, Barcelona, Spain; British Columbia Cancer Agency, Vancouver, British Columbia, Canada; Department of Medical Oncology, Hospital General Universitario de Elche, Alicante, Spain; Department of Medical Oncology, Instituto Valenciano de Oncologia, Valencia, Spain; National Cancer Institute of Canada Clinical Trials Group, Kingston, Ontario, Canada; Department of Medical Oncology, Hospital Universitario Virgen del Rocio, Seville, Spain; Department of Medical Oncology, Complejo Hospitalario Universitario A Coruña, Coruña, Spain; Department of Medical Oncology, Hospital Universitario Virgen de la Victoria, Málaga, Spain; GEICAM, Madrid, Spain; Sunnybrook Odette Cancer Centre, University of Toronto, Toronto, Ontario, Canada; McMaster University, Hamilton, Ontario, Canada; Department of Oncology, Tom Baker Cancer Centre, University of Calgary, Calgary, Alberta, Canada; Department of Pathology, University of Utah Health Sciences Center, Salt Lake City, Utah, USA; Department of Medicine, Washington University, St. Louis, Missouri, USA; Department of Oncology, Hospital of Prato, Istituto Toscani Tumori, Florence, Italy.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Ellis
authors.affiliation: Lineberger Comprehensive Cancer Center and Department of Genetics, University of North Carolina, Chapel Hill, North Carolina, USA; Clinical Trials and Statistics Unit at The Institute of Cancer Research, London, United Kingdom; Servicio de Oncología Médica, Instituto de Investigacion Sanitaria Hospital Universitario Gregorio Marañón, Facultad de Medicina, Universidad Complutense, Madrid, Spain; Department of Pathology, University of British Columbia, Vancouver, British Columbia, Canada; Translation Genomics Unit, Vall d´Hebron Institute of Oncology, Barcelona, Spain; British Columbia Cancer Agency, Vancouver, British Columbia, Canada; Department of Medical Oncology, Hospital General Universitario de Elche, Alicante, Spain; Department of Medical Oncology, Instituto Valenciano de Oncologia, Valencia, Spain; National Cancer Institute of Canada Clinical Trials Group, Kingston, Ontario, Canada; Department of Medical Oncology, Hospital Universitario Virgen del Rocio, Seville, Spain; Department of Medical Oncology, Complejo Hospitalario Universitario A Coruña, Coruña, Spain; Department of Medical Oncology, Hospital Universitario Virgen de la Victoria, Málaga, Spain; GEICAM, Madrid, Spain; Sunnybrook Odette Cancer Centre, University of Toronto, Toronto, Ontario, Canada; McMaster University, Hamilton, Ontario, Canada; Department of Oncology, Tom Baker Cancer Centre, University of Calgary, Calgary, Alberta, Canada; Department of Pathology, University of Utah Health Sciences Center, Salt Lake City, Utah, USA; Department of Medicine, Washington University, St. Louis, Missouri, USA; Department of Oncology, Hospital of Prato, Istituto Toscani Tumori, Florence, Italy.
authors.forename: Charles M
authors.initials: CM
authors.lastname: Perou
authors.affiliation: Lineberger Comprehensive Cancer Center and Department of Genetics, University of North Carolina, Chapel Hill, North Carolina, USA; Clinical Trials and Statistics Unit at The Institute of Cancer Research, London, United Kingdom; Servicio de Oncología Médica, Instituto de Investigacion Sanitaria Hospital Universitario Gregorio Marañón, Facultad de Medicina, Universidad Complutense, Madrid, Spain; Department of Pathology, University of British Columbia, Vancouver, British Columbia, Canada; Translation Genomics Unit, Vall d´Hebron Institute of Oncology, Barcelona, Spain; British Columbia Cancer Agency, Vancouver, British Columbia, Canada; Department of Medical Oncology, Hospital General Universitario de Elche, Alicante, Spain; Department of Medical Oncology, Instituto Valenciano de Oncologia, Valencia, Spain; National Cancer Institute of Canada Clinical Trials Group, Kingston, Ontario, Canada; Department of Medical Oncology, Hospital Universitario Virgen del Rocio, Seville, Spain; Department of Medical Oncology, Complejo Hospitalario Universitario A Coruña, Coruña, Spain; Department of Medical Oncology, Hospital Universitario Virgen de la Victoria, Málaga, Spain; GEICAM, Madrid, Spain; Sunnybrook Odette Cancer Centre, University of Toronto, Toronto, Ontario, Canada; McMaster University, Hamilton, Ontario, Canada; Department of Oncology, Tom Baker Cancer Centre, University of Calgary, Calgary, Alberta, Canada; Department of Pathology, University of Utah Health Sciences Center, Salt Lake City, Utah, USA; Department of Medicine, Washington University, St. Louis, Missouri, USA; Department of Oncology, Hospital of Prato, Istituto Toscani Tumori, Florence, Italy.
authors.forename: Angelo
authors.initials: A
authors.lastname: Di Leo
authors.affiliation: Lineberger Comprehensive Cancer Center and Department of Genetics, University of North Carolina, Chapel Hill, North Carolina, USA; Clinical Trials and Statistics Unit at The Institute of Cancer Research, London, United Kingdom; Servicio de Oncología Médica, Instituto de Investigacion Sanitaria Hospital Universitario Gregorio Marañón, Facultad de Medicina, Universidad Complutense, Madrid, Spain; Department of Pathology, University of British Columbia, Vancouver, British Columbia, Canada; Translation Genomics Unit, Vall d´Hebron Institute of Oncology, Barcelona, Spain; British Columbia Cancer Agency, Vancouver, British Columbia, Canada; Department of Medical Oncology, Hospital General Universitario de Elche, Alicante, Spain; Department of Medical Oncology, Instituto Valenciano de Oncologia, Valencia, Spain; National Cancer Institute of Canada Clinical Trials Group, Kingston, Ontario, Canada; Department of Medical Oncology, Hospital Universitario Virgen del Rocio, Seville, Spain; Department of Medical Oncology, Complejo Hospitalario Universitario A Coruña, Coruña, Spain; Department of Medical Oncology, Hospital Universitario Virgen de la Victoria, Málaga, Spain; GEICAM, Madrid, Spain; Sunnybrook Odette Cancer Centre, University of Toronto, Toronto, Ontario, Canada; McMaster University, Hamilton, Ontario, Canada; Department of Oncology, Tom Baker Cancer Centre, University of Calgary, Calgary, Alberta, Canada; Department of Pathology, University of Utah Health Sciences Center, Salt Lake City, Utah, USA; Department of Medicine, Washington University, St. Louis, Missouri, USA; Department of Oncology, Hospital of Prato, Istituto Toscani Tumori, Florence, Italy lisa_carey@med.unc.edu.
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Carey
mesh_terms: D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009367:Neoplasm Staging; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis / Q000235:genetics*; D011960:Receptors, Estrogen / Q000096:biosynthesis / Q000235:genetics*; D011980:Receptors, Progesterone / Q000096:biosynthesis / Q000235:genetics*; D064726:Triple Negative Breast Neoplasms / Q000145:classification / Q000235:genetics* / Q000473:pathology
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C508053:ERBB2 protein, human
keywords: Breast cancer; Intrinsic subtypes; Receptor expression