ERBB2 mutations associated with solid variant of high-grade invasive lobular breast carcinomas.
ERBB2 and ERBB3 somatic gain-of-function mutations, which may be targeted by anti-ERBB2 therapies, were reported by high-throughput sequencing studies in 1% and 2% of invasive breast cancers respectively. Our study aims to determine ERBB2 and ERBB3 mutations frequencies in grade 3 and/or ERBB2-positive invasive lobular breast carcinomas (ILC). All the 529 ILC surgically-excised registered at Institut Curie in the years 2005 to 2008 were reviewed. Thirty-nine grade 3 ERBB2-negative ILC and 16 ERBB2-positive ILC were retrieved and subjected to Sanger sequencing of the ERBB2 and ERBB3 activation mutation hotspots (ERBB2: exons 8, 17, 19, 20, 21; ERBB3: exons 3, 6, 7, 8). Among the 39 grade 3 ERBB2-negative ILC, six tumors were found to have at least one detectable ERBB2 activating mutation (incidence rate: 15%, 95%CI [4%-27%]). No ERBB2 mutation was found among the 16 ERBB2-positive ILC. No ERBB3 mutation was found in any of the 55 ILC. ERBB2 mutations were statistically associated with solid ILC features (p=0.01). Survival analyses showed no significant prognostic impact of ERBB2 mutations. Our study demonstrates that high grade ERBB2-negative ILC display a high frequency of ERBB2 mutations, and should be subjected to systematic genetic screening.
Institut Curie, PSL Research University, Pathology-Genetics-Immunology Department, 75005 Paris, France.
Gabrielle
G
Deniziaut
Geneva University Hospital, Faculty of Medicine, Division of Clinical Pathology, 1205 Geneva, Switzerland.
Jean Christophe
JC
Tille
Institut Curie, PSL Research University, Medical Oncology Department, 75005 Paris, France.
François-Clément
FC
Bidard
Institut Curie, PSL Research University, Pathology-Genetics-Immunology Department, 75005 Paris, France.
Sophie
S
Vacher
Institut Curie, PSL Research University, Pathology-Genetics-Immunology Department, 75005 Paris, France.
Anne
A
Schnitzler
Institut Curie, PSL Research University, Pathology-Genetics-Immunology Department, 75005 Paris, France.
Walid
W
Chemlali
Institut Curie, PSL Research University, Pathology-Genetics-Immunology Department, 75005 Paris, France.
Laurence
L
Trémoulet
Institut Curie, PSL Research University, Pathology-Genetics-Immunology Department, 75005 Paris, France.
Laetitia
L
Fuhrmann
Institut Curie, PSL Research University, Medical Oncology Department, 75005 Paris, France.
Paul
P
Cottu
Institut Curie, Versailles Saint-Quentin University, Surgery Department, 92210 Saint-Cloud, France.
Roman
R
Rouzier
Institut Curie, PSL Research University, Pathology-Genetics-Immunology Department, 75005 Paris, France.
Ivan
I
Bièche
Institut Curie, PSL Research University, Pathology-Genetics-Immunology Department, 75005 Paris, France.|Institut Curie, PSL Research University, INSERM U934, 75005 Paris, France.
Anne
A
Vincent-Salomon
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D018275:Carcinoma, Lobular / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*; D012189:Retrospective Studies
D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human
ERBB2 mutations; ERBB3 mutations; anti-ERBB2 targeted agents; invasive lobular breast carcinoma; sequencing