title: Comparison of the prognostic value of genomic grade index, Ki67 expression and mitotic activity index in early node-positive breast cancer patients.
abstract: Background The genomic grade index (GGI) completes the prognostic value of histological grade (HG). Other proliferation markers include the mitotic activity index (MAI) and the Ki67 immunohistochemistry (IHC) status. We compared the prognostic value of GGI, HG, MAI, Ki67 IHC and messenger RNA (mRNA) status in node-positive breast cancer (BC) patients treated with adjuvant anthracycline-based chemotherapy in the prospective PACS01 trial.  Patients and methods The five proliferation-related parameters (GGI, Ki67 mRNA expression and centrally determined HG, MAI, and Ki67 IHC status) of tumours were available for 204 cases and analysed as continuous values. We compared the correlations of each one with the other proliferation-related parameters and with histoclinical variables including the disease-free survival (DFS).  Results Expected correlations were observed between the five parameters and for each parameter with biological features (hormone-receptor and HER2 status, molecular subtypes), but the GGI displayed the strongest correlations. The GGI outperformed the prognostic performance of the four other proliferation-related parameters for the DFS in all 204 patients and in the 95 HG2 patients. In multivariate analysis including the classical prognostic factors, only GGI remained significant. Finally, the GGI outperformed the prognostic performance of MKI67 mRNA expression in a series of 1599 samples and 656 HG2 cases.  Conclusions In this small pilot biomarker study ancillary to the PACS01 trial, the GGI outperforms the prognostic performance of centrally determined HG, MAI, Ki67 IHC status and mRNA expression. Further validation is warranted in larger series.
authors.affiliation: Department of Molecular Oncology, Centre de Recherche en Cancérologie de Marseille, UMR1068 Inserm, Institut Paoli-Calmettes IPC, 13273 Marseille, France. bertuccif@ipc.unicancer.fr
authors.forename: F
authors.initials: F
authors.lastname: Bertucci
authors.forename: P
authors.initials: P
authors.lastname: Finetti
authors.forename: H
authors.initials: H
authors.lastname: Roche
authors.forename: J M
authors.initials: JM
authors.lastname: Le Doussal
authors.forename: L
authors.initials: L
authors.lastname: Marisa
authors.forename: A L
authors.initials: AL
authors.lastname: Martin
authors.forename: M
authors.initials: M
authors.lastname: Lacroix-Triki
authors.forename: C
authors.initials: C
authors.lastname: Blanc-Fournier
authors.forename: J
authors.initials: J
authors.lastname: Jacquemier
authors.forename: H
authors.initials: H
authors.lastname: Peyro-Saint-Paul
authors.forename: P
authors.initials: P
authors.lastname: Viens
authors.forename: C
authors.initials: C
authors.lastname: Sotiriou
authors.forename: D
authors.initials: D
authors.lastname: Birnbaum
authors.forename: F
authors.initials: F
authors.lastname: Penault-Llorca
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D018270:Carcinoma, Ductal, Breast / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D017326:Clinical Trials, Phase III as Topic; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism*; D008207:Lymphatic Metastasis; D008875:Middle Aged; D008940:Mitotic Index; D015999:Multivariate Analysis; D060787:Neoplasm Grading; D011379:Prognosis; D016016:Proportional Hazards Models; D012372:ROC Curve; D012189:Retrospective Studies
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen