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Updated: May 4, 2026

Studying Triple Negative Breast Cancer Using Orthotopic Breast Cancer Model
Published on: March 20, 2020
Triple negative breast carcinoma EGFR amplification is not associated with EGFR, Kras or ALK mutations
V Secq1, J Villeret2, F Fina3
11] Department of Pathology, AP-HM CHU Nord, Marseille, France [2] Aix-Marseille Université (AMU), 27 Boulevard Jean Moulin, 13385 Marseille Cedex 05, Marseille, France [3] INSERM U 1068 Stress Cellulaire, Campus de Luminy, Case 915, 13009, Marseille, France.
Background:
The amplification of epidermal growth factor receptor (EGFR) in triple negative breast carcinomas (TNBC) suggests its potential therapeutic application, as for HER-2, using standardised methods of measurement. In this regard, we aimed to compare several methods for evaluating EGFR amplification along with potential mutations for suitability in clinical practice.
Methods:
Tissue sections of 138 TNBCs were used (1) to compare EGFR amplification and expression by silver in situ hybridisation (SISH) to qPCR and immunohistochemistry (IHC) and (2) to search for EGFR mutations, along with Kras, PI3K, Braf and HER-2 mutations and echinoderm microtubule associated protein like 4-anaplastic lymphoma kinase (EML4-ALK) translocation.
Results:
(1) Amplification of EGFR was observed in well-characterised TNBCs (up to 92%); (2) qPCR correlated with SISH with 94% specificity and 75.6% sensitivity; (3) IHC correlated with SISH with 97% sensitivity and 78% specificity; (4) no EGFR, Kras mutations or EML4-ALK translocations were found, but PI3K and Braf mutations were observed in 26% of cases; and (5) small, acentric circular extrachromosomal DNA similar to 'double minutes' in glioblastomas was observed in 18% of SISH sections.
Conclusions:
SISH and IHC are methods that are suitable in clinical practice to screen for EGFR amplification and overexpression, which are frequently observed in TNBC. Patients with TNBC are potential candidates for EGFR-targeted therapy combined with PI3K and Braf inhibitors.
Insights
Epidermal growth factor receptor (EGFR) amplification is common in triple-negative breast cancer (TNBC). Silver in situ hybridization (SISH) and immunohistochemistry (IHC) are suitable clinical methods for screening, suggesting TNBC patients may benefit from targeted therapies.
Area of Science:
- Oncology
- Molecular Diagnostics
- Genetics
Background:
- Epidermal growth factor receptor (EGFR) amplification is prevalent in triple-negative breast cancer (TNBC).
- Standardized measurement methods are needed to assess EGFR amplification for potential therapeutic targeting in TNBC.
- This study evaluated various methods for detecting EGFR amplification and mutations in TNBC.
Purpose of the Study:
- To compare silver in situ hybridization (SISH), quantitative polymerase chain reaction (qPCR), and immunohistochemistry (IHC) for evaluating EGFR amplification in TNBC.
- To investigate the presence of mutations in EGFR, Kras, PI3K, Braf, and HER-2, as well as EML4-ALK translocations in TNBC.
- To assess the clinical suitability of different diagnostic methods for EGFR alterations in TNBC.
Main Methods:
- 138 TNBC tissue sections were analyzed.
- EGFR amplification and expression were compared using SISH, qPCR, and IHC.
- Mutation analysis included EGFR, Kras, PI3K, Braf, HER-2, and EML4-ALK translocation detection.
Main Results:
- EGFR amplification was detected in up to 92% of TNBC cases.
- qPCR showed 94% specificity and 75.6% sensitivity compared to SISH.
- IHC demonstrated 97% sensitivity and 78% specificity relative to SISH.
- PI3K and Braf mutations occurred in 26% of cases; no EGFR mutations or EML4-ALK translocations were found.
- Extrachromosomal DNA resembling 'double minutes' was observed in 18% of SISH sections.
Conclusions:
- SISH and IHC are clinically viable methods for screening EGFR amplification and overexpression in TNBC.
- Frequent EGFR amplification and overexpression in TNBC suggest potential for EGFR-targeted therapies.
- TNBC patients may benefit from combination therapies including EGFR, PI3K, and Braf inhibitors.
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