Journal Article

Respective Prognostic Value of Genomic Grade and Histological Proliferation Markers in Early Stage (pN0) Breast Carcinoma

Bollet, Marc A., Cottu, Paul, Gentien, David, Sigal-Zafrani, Brigitte, Caly, Martial, Dieras, Véronique, Carpentier, Sabrina, Sastre-Garau, Xavier, Pierga, Jean-Yves, Reyal, Fabien, Vincent-Salomon, Anne, Peyro-Saint-Paul, Hélène

2012

Overview

Genomic grade (GG) is a 97-gene signature which improves the accuracy and prognostic value of histological grade (HG) in invasive breast carcinoma. Since most of the genes included in the GG are involved in cell proliferation, we performed a retrospective study to compare the prognostic value of GG, Mitotic Index and Ki67 score. A series of 163 consecutive breast cancers was retained (pT1-2, pN0, pM0, 10-yr follow-up). GG was computed using MapQuant Dx(R). GG was low (GG-1) in 48%, high (GG-3) in 31% and equivocal in 21% of cases. For HG-2 tumors, 50% were classified as GG-1, 18% as GG-3 whereas 31% remained equivocal. In a subgroup of 132 ER+/HER2- tumors GG was the most significant prognostic factor in multivariate Cox regression analysis adjusted for age and tumor size (HR = 5.23, p = 0.02). In a reference comprehensive cancer center setting, compared to histological grade, GG added significant information on cell proliferation in breast cancers. In patients with HG-2 carcinoma, applying the GG to guide the treatment scheme could lead to a reduction in adjuvant therapy prescription. However, based on the results observed and considering (i) the relatively close prognostic values of GG and Ki67, (ii) the reclassification of about 30% of HG-2 tumors as Equivocal GG and (iii) the economical and technical requirements of the MapQuant micro-array GG test, the availability in the near future of a PCR-based Genomic Grade test with improved performances may lead to an introduction in clinical routine of this test for histological grade 2, ER positive, HER2 negative breast carcinoma.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Adult / Aged / Analysis / Biology / Breast / Breast cancer / Breast carcinoma / Breast Neoplasms - drug therapy / Breast Neoplasms - genetics / Breast Neoplasms - mortality / Breast Neoplasms - pathology / Cancer genetics / Cancer therapies / Carcinoma / Carcinoma - drug therapy / Carcinoma - genetics / Carcinoma - mortality / Carcinoma - pathology / Cell cycle / Cell growth / Cell proliferation / Chemotherapy / Clinical decision making / Clinical medicine / Decision making / ErbB-2 protein / Estrogen / Estrogens / Feasibility studies / Female / Follow-Up Studies / Gene expression / Genes / Genetic aspects / Genomics / Humans / Immunophenotyping / Invasiveness / Kaplan-Meier Estimate / Ki-67 Antigen - genetics / Ki-67 Antigen - metabolism / Laboratories / Medical prognosis / Medicine / Middle Aged / Mitotic Index / Neoplasm Metastasis / Neoplasm Staging / Prognosis / Quality / Reclassification / Regression analysis / Transcriptome / Tumors