title: Consistency and inconsistency in testing biomarkers in breast cancer. A GRELL study in cut-off variability in the Romance language countries.
abstract: OBJECTIVE
  Biological markers are crucial factors in order to differentiate female breast cancers and to determine the right therapy. This study aims at evaluating whether testing for biomarkers for female breast cancer has similar frequency and characteristics across and within countries.
  
  
  METHODS
  Population-based cancer registries of the Association for cancer registration and epidemiology in Romance language countries (GRELL) were asked to complete a questionnaire on biomarkers testing. The data collected referred to invasive female breast cancer cases diagnosed between 2004 and 2009. The investigation focused on 1) the overexpression and amplification of the human epidermal growth factor receptor 2 oncogene (HER2); 2) the expression of oestrogen (ER) and progesterone (PgR) receptors; and 3) the proliferation index (PI). Weighted percentages, the heterogeneity among and within countries, and the correlation between responses and calendar years were evaluated. The study was based on 19,644 breast cancers.
  
  
  RESULTS
  Overall, 85.9% of the cases were tested for HER2, 91.8% for both ER and PgR, and 74.1% for proliferative markers. For HER2 and ER-PgR, the frequency of testing increased from 2004 to 2009. Testing varied among countries (HER2 from 82.0% to 95.9%, ER-PgR from 89.3% to 98.9%, PI from 10% to 92%) and also within the same country (e.g. HER2 in Italy from 51% to 99%) as well as within single cancer registries. The most relevant differences were in the scores for positive/negative/not clearly defined HER2 (e.g. HER2 was defined positive if IHC 3+ in 21/33 registries), and in the cut-off of positive cells for ER/PgR (from >0% to >30%) and PI positivity (from >0% to >20%).
  
  
  CONCLUSIONS
  Biological markers are widely tested in the Romance language countries; however, the parameters defining their positivity may vary, raising concerns about homogeneity in breast cancer classification and treatment.
authors.affiliation: Tuscany Cancer Registry, Clinical and Descriptive Epidemiology Unit, ISPO Via delle Oblate 2, 50141 Florence, Italy.
authors.forename: Emanuele
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authors.lastname: Crocetti
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authors.lastname: Ferretti
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authors.lastname: Colombani
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authors.lastname: Guizard
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authors.lastname: Izarzugaza
authors.forename: Isabelle
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authors.lastname: Konzelmann
authors.forename: Francesco
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authors.lastname: La Rosa
authors.forename: Benedicte
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authors.lastname: Lapotre
authors.forename: Nathalie
authors.initials: N
authors.lastname: Leone
authors.forename: Karine
authors.initials: K
authors.lastname: Ligier
authors.forename: Lucia
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authors.lastname: Mangone
authors.forename: R
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authors.lastname: Marcos-Gragera
authors.forename: Ruth
authors.initials: R
authors.lastname: Martinez
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Michelena
authors.forename: Maria
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authors.lastname: Michiara
authors.forename: Ana
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authors.lastname: Miranda
authors.forename: Florence
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authors.lastname: Molinié
authors.forename: Conception
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authors.lastname: Mugarza-Gomez
authors.forename: Eugenio
authors.initials: E
authors.lastname: Paci
authors.forename: Silvano
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authors.lastname: Piffer
authors.forename: Montserrat
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authors.lastname: Puig-Vives
authors.forename: Claudio
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authors.lastname: Sacchettini
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Sánchez
authors.forename: Adele
authors.initials: A
authors.lastname: Traina
authors.forename: Brigitte
authors.initials: B
authors.lastname: Tretarre
authors.forename: Rosario
authors.initials: R
authors.lastname: Tumino
authors.forename: Elke
authors.initials: E
authors.lastname: Van Vaerenbergh
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authors.lastname: Velten
authors.forename: Anne S
authors.initials: AS
authors.lastname: Woronoff
mesh_terms: D001530:Belgium; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000378:metabolism; D049109:Cell Proliferation; D005260:Female; D005602:France; D006801:Humans; D007558:Italy; D011174:Portugal; D010818:Practice Patterns, Physicians' / Q000706:statistics & numerical data*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D012042:Registries; D012189:Retrospective Studies; D013030:Spain; D011795:Surveys and Questionnaires; D013557:Switzerland; D014583:Uruguay
chemical_list: D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C508053:ERBB2 protein, human