title: Heterogeneity of luminal breast cancer characterised by immunohistochemical expression of basal markers.
abstract: BACKGROUND
  Luminal A breast cancer defined as hormone receptor positive and human epidermal growth factor receptor 2 (HER2) negative is known to be heterogeneous. Previous study showed that luminal A tumours with the expression of basal markers ((cytokeratin (CK) 5 or CK5/6) or epidermal growth factor receptor (EGFR)) were associated with poorer prognosis compared with those that stained negative for basal markers. Prompted by this study, we assessed whether tumour characteristics and risk factors differed by basal marker status within luminal A tumours.
  
  
  METHODS
  We pooled 5040 luminal A cases defined by immunohistochemistry (4490 basal-negative ((CK5 (or CK5/6))- and EGFR-) and 550 basal-positive ((CK5 (or CK5/6+)) or EGFR+)) from eight studies participating in the Breast Cancer Association Consortium. Case-case comparison was performed using unconditional logistic regression.
  
  
  RESULTS
  Tumour characteristics and risk factors did not vary significantly by the expression of basal markers, although results suggested that basal-positive luminal tumours tended to be smaller and node negative, and were more common in women with a positive family history and lower body mass index.
  
  
  CONCLUSIONS
  Most established breast cancer risk factors were similar in basal-positive and basal-negative luminal A tumours. The non-significant but suggestive differences in tumour features and family history warrant further investigations.
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, 9609 Medical Center Drive, Bethesda, 20850 MD, USA.
authors.forename: Hyuna
authors.initials: H
authors.lastname: Sung
authors.affiliation: Division of Breast Cancer Research, Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, 15 Cotswold Rd, Sutton, Surrey, SM2 5NG London, UK.
authors.forename: Montserrat
authors.initials: M
authors.lastname: Garcia-Closas
authors.affiliation: Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
authors.forename: Jenny
authors.initials: J
authors.lastname: Chang-Claude
authors.affiliation: Department of Oncology, University of Cambridge, Worts Causeway, CB1 8RN Cambridge, UK.
authors.forename: Fiona M
authors.initials: FM
authors.lastname: Blows
authors.affiliation: Cancer Research UK Cambridge Institute, University of Cambridge, Robinson Way, CB2 0RE Cambridge, UK.
authors.forename: H Raza
authors.initials: HR
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authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, 9609 Medical Center Drive, Bethesda, 20850 MD, USA.
authors.forename: Jonine
authors.initials: J
authors.lastname: Figueroa
authors.affiliation: Department of Obstetrics and Gynecology, Helsinki University Hospital and University of Helsinki, PO Box 700, 00029 HUS Helsinki, Finland.
authors.forename: Heli
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authors.lastname: Nevanlinna
authors.affiliation: Department of Obstetrics and Gynecology, Helsinki University Hospital and University of Helsinki, PO Box 700, 00029 HUS Helsinki, Finland.
authors.forename: Rainer
authors.initials: R
authors.lastname: Fagerholm
authors.affiliation: Department of Pathology, Helsinki University Hospital and University of Helsinki, PO Box 400, 00029 Helsinki, Finland.
authors.forename: Päivi
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authors.lastname: Heikkilä
authors.affiliation: Department of Oncology, Helsinki University Hospital and University of Helsinki, PO Box 400, 00029 Helsinki, Finland.
authors.forename: Carl
authors.initials: C
authors.lastname: Blomqvist
authors.affiliation: Cancer Epidemiology Centre, Cancer Council Victoria, 615 St Kilda Rd, Melbourne, 3004 Victoria, Australia.|Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, 3010 Victoria, Australia.
authors.forename: Graham G
authors.initials: GG
authors.lastname: Giles
authors.affiliation: Cancer Epidemiology Centre, Cancer Council Victoria, 615 St Kilda Rd, Melbourne, 3004 Victoria, Australia.|Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, 3010 Victoria, Australia.
authors.forename: Roger L
authors.initials: RL
authors.lastname: Milne
authors.affiliation: Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Melbourne, 3010 Victoria, Australia.
authors.forename: Melissa C
authors.initials: MC
authors.lastname: Southey
authors.affiliation: Anatomical Pathology, The Alfred Hospital, Commercial Rd, Prahran, 3181, 3053 Victoria, Australia.
authors.forename: Catriona
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authors.lastname: McLean
authors.affiliation: School of Medicine, Institute of Clinical Medicine, Pathology and Forensic Medicine, Cancer Center of Eastern Finland, University of Eastern Finland, Yliopistonranta 1, PO Box 1627, 70211 Kuopio, Finland.|Department of Clinical Pathology, Imaging Center, Kuopio University Hospital, PO Box 100, 70029 KYS Kuopio, Finland.
authors.forename: Arto
authors.initials: A
authors.lastname: Mannermaa
authors.affiliation: School of Medicine, Institute of Clinical Medicine, Pathology and Forensic Medicine, Cancer Center of Eastern Finland, University of Eastern Finland, Yliopistonranta 1, PO Box 1627, 70211 Kuopio, Finland.|Department of Clinical Pathology, Imaging Center, Kuopio University Hospital, PO Box 100, 70029 KYS Kuopio, Finland.
authors.forename: Veli-Matti
authors.initials: VM
authors.lastname: Kosma
authors.affiliation: Jyväskylä Central Hospital, Central Finland Health Care District, Adm Bldg 6/2, Keskussairaalantie 19, 40620 Jyväskylä, Finland.
authors.forename: Vesa
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authors.lastname: Kataja
authors.affiliation: School of Medicine, Institute of Clinical Medicine, Pathology and Forensic Medicine, Cancer Center of Eastern Finland, University of Eastern Finland, Yliopistonranta 1, PO Box 1627, 70211 Kuopio, Finland.|Department of Clinical Pathology, Imaging Center, Kuopio University Hospital, PO Box 100, 70029 KYS Kuopio, Finland.
authors.forename: Reijo
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authors.lastname: Sironen
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Stabile 2-42, 200 First Street SW, Rochester, 55905 MN, USA.
authors.forename: Fergus J
authors.initials: FJ
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authors.affiliation: Department of Health Sciences Research, Mayo Clinic, 200 First St SW, Rochester, 55905 MN, USA.
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authors.initials: JE
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authors.affiliation: Department of Health Sciences Research, Mayo Clinic, 200 First St SW, Rochester, 55905 MN, USA.
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authors.affiliation: Department of Health Sciences Research, Mayo Clinic, 200 First St SW, Rochester, 55905 MN, USA.
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authors.affiliation: Sheffield Cancer Research, Department of Oncology, University of Sheffield, Beech Hill Road, S10 2RX Sheffield, UK.
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authors.affiliation: Department of Neuroscience, University of Sheffield, Beech Hill Road, S10 2RX Sheffield, UK.
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authors.initials: SS
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authors.affiliation: Program in Genetic Epidemiology and Statistical Genetics, Harvard T.H. Chan School of Public Health, 677 Huntington Avenue, Boston, 02115 MA, USA.
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authors.affiliation: Department of Medicine, Channing Division of Network Medicine, Harvard Medical School and Brigham and Women's Hospital, 181 Longwood Avenue, Boston, 02115 MA, USA.|Department of Epidemiology, Harvard T.H. Chan School of Public Health, 677 Huntington Ave, Boston, 02115 MA, USA.
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authors.affiliation: Department of Medicine, Channing Division of Network Medicine, Harvard Medical School and Brigham and Women's Hospital, 181 Longwood Avenue, Boston, 02115 MA, USA.|Department of Epidemiology, Harvard T.H. Chan School of Public Health, 677 Huntington Ave, Boston, 02115 MA, USA.
authors.forename: A Heather
authors.initials: AH
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authors.affiliation: Department of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of Cambridge, CB1 8RN Cambridge, UK.
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authors.affiliation: Department of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of Cambridge, CB1 8RN Cambridge, UK.
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authors.affiliation: Department of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of Cambridge, CB1 8RN Cambridge, UK.|Department of Oncology, Centre for Cancer Genetic Epidemiology, University of Cambridge, Strangeways Research Laboratory, Worts Causeway, CB1 8RN Cambridge, UK.
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authors.initials: D
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authors.affiliation: Cancer Research UK Cambridge Institute, Li Ka Shing Centre, CB2 0RE Cambridge, UK.
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authors.affiliation: Division of Genetics and Epidemiology, The Institute of Cancer Research, 15 Cotswold Rd, Sutton, Surrey, SM2 5NG London, UK.
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authors.affiliation: Department of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of Cambridge, CB1 8RN Cambridge, UK.|Department of Oncology, Centre for Cancer Genetic Epidemiology, University of Cambridge, Strangeways Research Laboratory, Worts Causeway, CB1 8RN Cambridge, UK.
authors.forename: Paul D P
authors.initials: PD
authors.lastname: Pharoah
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, 9609 Medical Center Drive, Bethesda, 20850 MD, USA.
authors.forename: Mark E
authors.initials: ME
authors.lastname: Sherman
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, 9609 Medical Center Drive, Bethesda, 20850 MD, USA.
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mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015992:Body Mass Index; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism* / Q000473:pathology; D018275:Carcinoma, Lobular / Q000378:metabolism* / Q000473:pathology; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053555:Keratin-5 / Q000378:metabolism*; D053553:Keratin-6 / Q000378:metabolism*; D008572:Menarche; D008593:Menopause; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D010298:Parity; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000378:metabolism*; D012307:Risk Factors; D047368:Tumor Burden
chemical_list: D014408:Biomarkers, Tumor; D066246:ErbB Receptors; D053555:Keratin-5; D053553:Keratin-6; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C512478:EGFR protein, human; C508053:ERBB2 protein, human