Abstract P3-10-09: Genomic Grade Index (GGI): Tumor Grading Performance and Prognostic Value Compared to Ki67 and Mitotic Index in Early Invasive Breast Cancer — A Reference Centre Experience

Author(s):  
F Reyal ◽  
M Bollet ◽  
M Caly ◽  
D Hajage ◽  
S Carpentier ◽  
...  
2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 11094-11094
Author(s):  
F. Bertucci ◽  
J. M. Le Doussal ◽  
D. Birnbaum ◽  
R. Tagett ◽  
A. Martinec ◽  
...  

11094 Background: Genomic grading has been proposed to improve tumor grading. The genomic grade index (GGi) is a 97-gene continuous measure which resolves 80% of histological grade 2 (HG 2) tumors into HG 1 and HG 3 risk categories. GGi has higher prognostic value than HG in patients treated with and without systemic adjuvant endocrine and chemotherapy. A key issue is whether the GGi adds prognostic information to centrally-determined mitotic index and Ki-67 IHC. Methods: The control arm of the PACS 01 trial included 996 women with node-positive (N+) early breast cancer treated with six cycles of fluorouracil, epirubicin, and cyclophosphamide (FEC) and tamoxifen as required. 128 genomic profiles could be obtained from available frozen tumor samples using Affymetrix U133 Plus 2.0 gene chips through the “Carte d'Identite des Tumeurs” program of the French Ligue Nationale contre le Cancer. The Genomic Grade index (GGi) was computed using Ipsogen MapQuant Dx(R). Central Elston-Ellis grade, mitotic index (mitosis / mm2), and Ki-67 IHC (% positive cells) were available for 125 patients. The GGi and histological parameters were correlated to the 5-year metastasis status (MFS-5) by ROC analysis and to the metastasis hazard (follow-up of 6.2 ± years) by Cox regression. Results: In ER+ patients (n=93), the GGi was the only significant correlate to metastasis hazard in multivariate Cox regression with histological parameters (HR = 3.5 [1.7–7.5], p<0.001). It was the best predictor of MFS-5 (ROC AUC = 0.83, p=1E-6) when compared to histological parameters (ROC AUC = 0.71, 0.72 and 0.66 resp. p=0.003 to 0.03). In HG 2 subgroup (n=43), the GGi was the only significant predictor of MFS-5 (ROC AUC = 0.81, p=0.016). Conclusions: In our sample of N+ ER+ breast cancer patients, the GGi improved prognostication compared to centrally-measured mitotic index and Ki-67 IHC used alone and in combination. Moreover, the GGi was the only prognostic factor in histological grade 2 patients. [Table: see text]


2007 ◽  
Vol 29 (1) ◽  
pp. 25-35
Author(s):  
Emiel A. M. Janssen ◽  
Håvard Søiland ◽  
Ivar Skaland ◽  
Einar Gudlaugson ◽  
Kjell H. Kjellevold ◽  
...  

Background: The prognostic value of the PI3K/Akt/mTOR pathway and PTEN in invasive breast cancer (IBC) is controversial. Cell proliferation, especially the Mitotic Activity Index (MAI), is strongly prognostic in lymph node-negative (LNneg) invasive breast cancer. However, its prognostic value has not been compared with the value of Akt and PTEN expression. Material and Methods: Prognostic comparison of Her2Neu, p110alpha (PIK3CA), Akt, mTOR, PTEN, MAI and cell-cycle regulators in 125 LNneg patients aged <55 years with cyclophosphamide, methotrexate, and 5-fluorouracil (CMF)-based adjuvant systemic chemotherapy. Results: Twenty-one (17%) patients developed distant metastases = DMs (median follow-up: 134 months). p110alpha correlated (p = 0.01) with pAkt but only in PTEN-negatives; pAkt correlated (p = 0.02) with mTOR. PTEN-negativity correlated with high MAI, high grade and ER-negativity (p = 0.009). The MAI was the strongest prognosticator (Hazard Ratio = HR = 2.9, p = 0.01). Her2Neu/p110α/Akt/mTOR features have no additional prognostic value to the MAI. PTEN had additional value but only in MAI < 3 (39/125 = 31%; 8% DMs). 19/39 = 49% of the MAI < 3 patients have combined MAI < 3 / PTEN+ with 0% DMs, contrasting 15% DMs in MAI < 3 / PTEN− (p = 0.03). Conclusions: In T1−3N0M0 adjuvant CMF-treated breast cancer patients aged <55 years, MAI was the strongest survival predictor. The PI3K/Akt/mTOR pathway and cell-cycle regulator characteristics had no additional prognostic value, but PTEN has. Patients with combined MAI < 3 & PTEN-positivity had 100% survival. The small subgroup of MAI < 3 patients that died were PTEN-negative.


2003 ◽  
Author(s):  
Qifeng Yang ◽  
Takeo Sakurai ◽  
Goro Yoshimura ◽  
Takaomi Suzuma ◽  
Teiji Umemura ◽  
...  

Author(s):  
I. Quintela ◽  
M. Corte ◽  
M. Allende ◽  
J. Vazquez ◽  
J. Rodríguez ◽  
...  

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 21058-21058 ◽  
Author(s):  
V. Durbecq ◽  
J. Toussaint ◽  
B. Haibe-Kains ◽  
C. Desmedt ◽  
G. Rouas ◽  
...  

21058 Background: We have recently shown that proliferation captured by the genomic grade index (GGI) is the most important prognostic factor in BC, far beyond estrogen receptor (ER) status and may encompass a significant portion of the predictive power of many previously published prognostic signatures. Furthermore, we have demonstrated that GGI can identify two clinically distinct ER-positive molecular subtypes in a simple and highly reproducible manner across multiple datasets. The aims of this study were to convert and validate by qRT-PCR assay the prognostic value of the GGI using frozen (FS) and paraffin-embedded tumor samples (FFPE) from early BC patients. Methods: We first developed a qRT-PCR assay based on 8 selected GGI genes involved in different phases of the cell cycle and 4 reference genes. We then tested its accuracy and concordance with the original microarray derived GGI using a BC population from which FS, FFPE tissues and microarray data were available (N=30). Finally, we assessed its prognostic value on an independent ER-positive tamoxifen only treated BC population (N=82). Results: A statistically significant correlation was observed between GGI generated by microarray and qRT-PCR assay using FS material (r=0.91; p<0.0001) as well as between GGI using qRT-PCR derived from FS and FFPE tumor samples (r=0.86; p<0.0001). A high GGI levels assessed by qRT-PCR (GGRI) was associated with a higher risk of recurrence in the ER-positive tamoxifen only treated patients [HR= 2.319 (95% CI: 1.245–4.321), p=0.008] in accordance with our previous microarray results. Interestingly, in a multivariate analysis, GGRI remained significant [HR=1.956 (95% CI: 1.031–3.710), p=0.04] together with age (<50y) and tumor size (>2cm). Conclusions: In this study, we report a qRT-PCR assay based on a limited number of genes, which recapitulates in an accurate and reproducible manner the prognostic power of the microarray derived GGI using both FS and FFPE tumor samples. Further validation of its prognostic value is currently ongoing on two independent populations totaling over 500 BC patients. No significant financial relationships to disclose.


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