High EGFR protein expression and exon 9 PIK3CA mutations are independent prognostic factors in triple negative breast cancers

BMC Cancer

Research Article

Caroline Mollevi¹  Gilles Romieu²  William Jacot³  Frédéric Fina⁴  Pierre-Marie Martin⁴  Pierre-Jean Lamy⁵  Frédéric Bibeau⁶  Pierre-Emmanuel Colombo⁷  Evelyne Lopez-Crapez⁸ 

[1] Biostatistical Research Unit, Montpellier Cancer Institute Val d’Aurelle, 208, rue des Apothicaires, F-34298, Montpellier, France;Department of Medical Oncology, Montpellier Cancer Institute Val d’Aurelle, 208, rue des Apothicaires, F-34298, Montpellier, France;Department of Medical Oncology, Montpellier Cancer Institute Val d’Aurelle, 208, rue des Apothicaires, F-34298, Montpellier, France;Translationnal Research Unit, Montpellier Cancer Institute Val d’Aurelle, 208, rue des Apothicaires, F-34298, Montpellier, France;Department of Oncobiology, Assistance Publique – Hôpitaux de Marseille, Boulevard Pierre Dramard, F-13916, Marseille, France;Department of Oncogenetics, Montpellier Cancer Institute Val d’Aurelle, 208, rue des Apothicaires, F-34298, Montpellier, France;Biological Ressources Center, Montpellier Cancer Institute Val d’Aurelle, 208, rue des Apothicaires, F-34298, Montpellier, France;Department of Pathology, Montpellier Cancer Institute Val d’Aurelle, 208, rue des Apothicaires, F-34298, Montpellier, France;Department of Surgical Oncology, Montpellier Cancer Institute Val d’Aurelle, 208, rue des Apothicaires, F-34298, Montpellier, France;Translationnal Research Unit, Montpellier Cancer Institute Val d’Aurelle, 208, rue des Apothicaires, F-34298, Montpellier, France;

关键词: Triple negative;    Breast cancer;    EGFR;    Gene amplification;    PI3K;    PTEN;   

DOI  :  10.1186/s12885-015-1977-3

 received in 2015-07-03, accepted in 2015-12-05,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundTriple negative breast cancers (TNBC) are a more aggressive subset of breast cancer. A better understanding of its biology could allow the rational development of targeted therapies.MethodsWe extensively analyzed the EGFR/PI3K/PTEN axis in a large, homogeneous population of TNBC to help defining the putative role of anti-EGFR and -PI3K targeted therapies in this setting. EGFR gene amplification, EGFR protein expression, PIK3CA and PTEN gene alterations (two members of EGFR downstream pathways) and their clinicopathological and prognostic implications were analyzed in 204 TNBC samples from European patients.ResultsEGFR amplification was detected in 18 of the 204 TNBC specimens (8.9 %) and was significantly associated with higher EGFR protein levels. Fourteen PIK3CA mutations were identified in exon 9 (6.7 %), and 17 in exon 20 (8.3 %). PIK3CA mutations, especially in exon 9, were significantly associated with grade I-II tumors. PTEN deletions were detected in 43 samples (21.50 %) and were significantly associated with grade III tumors (p < 0.001). Univariate analysis showed a significant association between relapse-free survival (RFS), T and N stage and exon 9 PIK3CA mutations. Overall survival was significantly associated with T stage, N stage and adjuvant chemotherapy, which was administered to 70.3 % of patients. In multivariate analyses, T stage, N stage, presence of exon 9 PIK3CA mutations and high EGFR protein level were independent poor prognostic factors for RFS, while adjuvant chemotherapy was associated with a better outcome.ConclusionsHigh EGFR protein expression and exon 9 PIK3CA activating mutations are independent prognostic factors in TNBC. The efficacy of anti-PI3K targeted therapies needs to be evaluated in this setting.

【 授权许可】

CC BY   
© Jacot et al. 2015