Improvement of the clinical applicability of the Genomic Grade Index through a qRT-PCR test performed on frozen and formalin-fixed paraffin-embedded tissues.

Full Abstract

BACKGROUND: Proliferation and tumor differentiation captured by the genomic grade index (GGI) are important prognostic indicators in breast cancer (BC) especially for the estrogen receptor positive (ER+) disease. The aims of this study were to convert this microarray index to a qRT-PCR assay (PCR-GGI), which could be realized on formalin fixed paraffin embedded samples (FFPE), and to assess its prognostic performance and predictive value of clinical benefit in early and advanced ER+ BC patients treated with tamoxifen. METHODS: The accuracy and concordance of the PCR-GGI with the GGI was assessed using BC patients for which frozen and FFPE tissues as well as microarray data were available (n = 19). The evaluation of the prognostic value of the PCR-GGI was assessed on FFPE material using a consecutive series of 212 systemically treated early BC patients. The predictive performance for tamoxifen benefit was assessed using two ER+ BC populations treated either with adjuvant tamoxifen only (n = 77+139) or first-line tamoxifen for advanced disease (n = 270). RESULTS: The PCR-GGI is based on the expression of 8 genes (4 representative of the GGI and 4 reference genes). A significant correlation was observed between the microarray-derived GGI and the qRT-PCR assay using frozen (rho = 0.95, p < 10E-06) and FFPE material (rho = 0.89, p < 10E-06). The prognostic performance of the PCR-GGI was confirmed on FFPE samples (HRunivar. = 1.89; [95CI:1.01-3.54], p = 0.05). The PCR-GGI further identified two subgroups of patients with statistically different time to distant metastasis free survival (DMFS) across the two cohorts of ER+ BC patients treated with adjuvant tamoxifen. Additionally, the PCR-GGI was associated with response to tamoxifen in the advanced setting (HRunivar. = 1.98; [95CI:1.51-2.59], p = 6.9E-07). CONCLUSION: PCR-GGI recapitulates in an accurate and reproducible manner the performances of the GGI using frozen and FFPE samples.

Author information

Author/s: Toussaint, Jérôme (J); Sieuwerts, Anieta M (AM); Haibe-Kains, Benjamin (B); Desmedt, Christine (C); Rouas, Ghizlane (G); Harris, Adrian L (AL); Larsimont, Denis (D); Piccart, Martine (M); Foekens, John A (JA); Durbecq, Virginie (V); Sotiriou, Christos (C);

Affiliation: Translational Research Unit, Jules Bordet Institute, Brussels, Belgium. jerome.toussaint(-atsign-)bordet.be

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: BMC genomics (BMC Genomics), published in England. (Language: eng)

Reference: 2009-; vol 10 (issue ) : pp 424

Dates: Created 2009/10/05; Completed 2009/10/30;

PMID: 19744330, status: MEDLINE (last retrieval date: 10/30/2009, IMS Date: )

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