Relapsed classic E-cadherin (CDH1) mutated invasive lobular breast cancer demonstrates a high frequency of HER2 (ERBB2) gene mutations
A partir d'échantillons tumoraux prélevés sur 22 patientes atteintes d'un carcinome lobulaire invasif récidivant, cette étude montre que les tumeurs présentant une mutation du gène CDH1 sont associées à de fréquentes mutations du gène HER2
Purpose: We queried whether comprehensive genomic profiling using a next generation sequencing (NGS)-based assay could identify novel and unanticipated targets of therapy for patients with relapsed invasive lobular carcinoma (ILC). Experimental Design: DNA sequencing (Illumina HiSeq 2000) was performed for 3,320 exons of 182 cancer-related genes and 37 introns of 14 genes frequently rearranged in cancer on indexed, adaptor ligated, hybridization-captured libraries using DNA isolated from FFPE sections from 22 histologically verified ILC. Results: A total of 75 genomic alterations were identified with an average of 3.4 alterations per tumor (range 1-6), of which 35 were actionable for an average of 1.59 actionable alterations per patient (range 0-3). Nineteen of 22 (86%) of the ILC samples harbored at least one actionable alteration. Six (27%) cases featured alterations in ERRB2 including 4 (18%) with ERBB2 mutation, 1 (5%) with an ERBB2 gene fusion and 1 (5%) with an ERBB2 copy number gain (amplification). The enrichment of ERBB2 mutations/fusion in CDH1 mutated ILC (5/22, 23%) compared with the 5 ERBB2 mutations in a series of 286 non-CDH1 mutated breast cancers from which the ILC cases were obtained (5/286, 2%) was significant (p=0.0006). Conclusions: Comprehensive genomic profiling of relapsed CDH1 mutated ILC revealed actionable genomic alterations in 82% of cases, featured a high incidence of ERBB2 alterations and can reveal actionable alterations that can inform treatment decisions for ILC patients.