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. 2016 Nov 8;7(45):73337-73346.
doi: 10.18632/oncotarget.11819.

ERBB2 mutations associated with solid variant of high-grade invasive lobular breast carcinomas

Gabrielle Deniziaut  1 , Jean Christophe Tille  2 , François-Clément Bidard  3 , Sophie Vacher  1 , Anne Schnitzler  1 , Walid Chemlali  1 , Laurence Trémoulet  1 , Laetitia Fuhrmann  1 , Paul Cottu  3 , Roman Rouzier  4 , Ivan Bièche  1 , Anne Vincent-Salomon  1   5
Affiliations

ERBB2 mutations associated with solid variant of high-grade invasive lobular breast carcinomas

Gabrielle Deniziaut et al. Oncotarget. .

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.

Keywords: ERBB2 mutations; ERBB3 mutations; anti-ERBB2 targeted agents; invasive lobular breast carcinoma; sequencing.

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Conflict of interest statement

CONFLICTS OF INTEREST

The authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1. Study flow chart
Figure 2
Figure 2. Mutations identified in a series of 55 invasive lobular carcinomas
a. Electropherograms of 3 cases with ERBB2 mutation. b. Distribution of ERBB2 mutations
Figure 3
Figure 3. Survival analysis in the mutated and wild-type ERBB2 patients subgroups
a. Breast cancer free interval (BCFi) analysis. b. Breast cancer specific survival (BCSS) analysis
See this image and copyright information in PMC

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