title: Genomic grade adds prognostic value in invasive lobular carcinoma.
abstract: BACKGROUND
  The prognostic value of histologic grade (HG) in invasive lobular carcinoma (ILC) remains uncertain, and most ILC tumors are graded as HG2. Genomic grade (GG) is a 97-gene signature that improves the prognostic value of HG. This study evaluates whether GG may overcome the limitations of HG in ILC.
  
  
  METHODS
  Gene expression data were generated from frozen tumor samples, and GG calculated according to the expression of 97 genes. The prognostic value of GG was assessed in a stratified Cox regression model for invasive disease-free survival (IDFS) and overall survival (OS).
  
  
  RESULTS
  A total of 166 patients were classified by GG. HG classified 33 (20%) tumors as HG1, 120 (73%) as HG2 and 12 (7%) as HG3. GG classified 106 (64%) tumors as GG low (GG1), 29 (17%) as GG high (GG3) and 31 (19%) as equivocal (cases not classified as GG1 or GG3). The median follow-up time was 6.5 years. In multivariate analyses, GG was associated with IDFS [HR(GG3 vs GG1) 5.6 (2.1-15.3); P < 0.001] and OS [HR(GG3 vs GG1) 7.2, 95% CI (1.6-32.2); P = 0.01].
  
  
  CONCLUSIONS
  GG outperformed HG in ILC and added prognostic value to classic clinicopathologic variables, including nodal status.
authors.affiliation: Breast Cancer Translation Research Laboratory J. C. Heuson, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: O
authors.initials: O
authors.lastname: Metzger-Filho
authors.affiliation: Breast Cancer Translation Research Laboratory J. C. Heuson, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: S
authors.initials: S
authors.lastname: Michiels
authors.affiliation: Department of Molecular Oncology, Institut Paoli-Calmettes, Marseille.
authors.forename: F
authors.initials: F
authors.lastname: Bertucci
authors.affiliation: Ipsogen SA, Marseille, France.
authors.forename: A
authors.initials: A
authors.lastname: Catteau
authors.affiliation: Breast Cancer Translation Research Laboratory J. C. Heuson, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: R
authors.initials: R
authors.lastname: Salgado
authors.affiliation: Department of Pathology, Cliniques Universitaires Saint Luc, Brussels, Belgium.
authors.forename: C
authors.initials: C
authors.lastname: Galant
authors.affiliation: Breast Cancer Translation Research Laboratory J. C. Heuson, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: D
authors.initials: D
authors.lastname: Fumagalli
authors.affiliation: Breast Cancer Translation Research Laboratory J. C. Heuson, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: S K
authors.initials: SK
authors.lastname: Singhal
authors.affiliation: Breast Cancer Translation Research Laboratory J. C. Heuson, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: C
authors.initials: C
authors.lastname: Desmedt
authors.affiliation: Breast Cancer Translation Research Laboratory J. C. Heuson, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: M
authors.initials: M
authors.lastname: Ignatiadis
authors.affiliation: Breast Cancer Translation Research Laboratory J. C. Heuson, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: S
authors.initials: S
authors.lastname: Haussy
authors.affiliation: Department of Molecular Oncology, Institut Paoli-Calmettes, Marseille.
authors.forename: P
authors.initials: P
authors.lastname: Finetti
authors.affiliation: Department of Molecular Oncology, Institut Paoli-Calmettes, Marseille.
authors.forename: D
authors.initials: D
authors.lastname: Birnbaum
authors.affiliation: Breast Cancer Translation Research Laboratory J. C. Heuson, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: K S
authors.initials: KS
authors.lastname: Saini
authors.affiliation: Department of Pathology, Cliniques Universitaires Saint Luc, Brussels, Belgium.
authors.forename: M
authors.initials: M
authors.lastname: Berlière
authors.affiliation: Breast Cancer Translation Research Laboratory J. C. Heuson, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: I
authors.initials: I
authors.lastname: Veys
authors.affiliation: Breast Cancer Translation Research Laboratory J. C. Heuson, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: E
authors.initials: E
authors.lastname: de Azambuja
authors.affiliation: Breast Cancer Translation Research Laboratory J. C. Heuson, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: I
authors.initials: I
authors.lastname: Bozovic
authors.affiliation: Ipsogen SA, Marseille, France.
authors.forename: H
authors.initials: H
authors.lastname: Peyro-Saint-Paul
authors.affiliation: Breast Cancer Translation Research Laboratory J. C. Heuson, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: D
authors.initials: D
authors.lastname: Larsimont
authors.affiliation: Breast Cancer Translation Research Laboratory J. C. Heuson, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: M
authors.initials: M
authors.lastname: Piccart
authors.affiliation: Breast Cancer Translation Research Laboratory J. C. Heuson, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium. Electronic address: christos.sotiriou@bordet.be.
authors.forename: C
authors.initials: C
authors.lastname: Sotiriou
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D018275:Carcinoma, Lobular / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D015870:Gene Expression; D006801:Humans; D053208:Kaplan-Meier Estimate; D019394:Ki-67 Antigen / Q000378:metabolism; D008875:Middle Aged; D015999:Multivariate Analysis; D060787:Neoplasm Grading; D011379:Prognosis; D016016:Proportional Hazards Models; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D016019:Survival Analysis; D046888:Tissue Array Analysis; D059467:Transcriptome
chemical_list: D019394:Ki-67 Antigen; D018719:Erb-b2 Receptor Tyrosine Kinases