Abstract |
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.
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Authors | Gabrielle Deniziaut, Jean Christophe Tille, François-Clément Bidard, Sophie Vacher, Anne Schnitzler, Walid Chemlali, Laurence Trémoulet, Laetitia Fuhrmann, Paul Cottu, Roman Rouzier, Ivan Bièche, Anne Vincent-Salomon |
Journal | Oncotarget
(Oncotarget)
Vol. 7
Issue 45
Pg. 73337-73346
(Nov 08 2016)
ISSN: 1949-2553 [Electronic] United States |
PMID | 27602491
(Publication Type: Journal Article)
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Chemical References |
- Biomarkers, Tumor
- ERBB2 protein, human
- Receptor, ErbB-2
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Topics |
- Adult
- Aged
- Aged, 80 and over
- Biomarkers, Tumor
- Breast Neoplasms
(genetics, mortality, pathology)
- Carcinoma, Lobular
(genetics, mortality, pathology)
- DNA Mutational Analysis
- Female
- Humans
- Middle Aged
- Mutation
- Neoplasm Grading
- Neoplasm Staging
- Prognosis
- Receptor, ErbB-2
(genetics)
- Retrospective Studies
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