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Updated: May 23, 2026
Optimization of a Multiplex RNA-based Expression Assay Using Breast Cancer Archival Material
Published on: August 1, 2018
Molecular characterization of EGFR and EGFR-downstream pathways in triple negative breast carcinomas with basal like
V Martin1, F Botta, E Zanellato
1Institute of Pathology, Locarno, Switzerland. vittoria.martin@ti.ch
Aims:
Triple negative breast cancer with basal like features (TN-BCBL) do not benefit from hormonal and anti-HER2 therapies. As a considerable fraction of TN-BCBLs shows EGFR deregulation, EGFR-targeted therapies have been proposed as an option. The characterization of EGFR and EGFR-downstream members may therefore provide important predictive information.
Methods And Results:
Based on morphological and immunophenotypic features, we identified 38 TN-BCBLs that were subsequently investigated for alterations in EGFR signaling pathways. EGFR and PTEN protein levels were studied by immunohistochemistry, EGFR gene status by FISH, EGFR, H-Ras, K-Ras, N-Ras, BRAF and PIK3CA gene mutations by direct sequencing. EGFR overexpression and loss of PTEN expression characterized the majority of TN-BCBLs (76% and 74% of patients, respectively). EGFR gene copy number gain (FISH+) was identified in 51% of analyzable patients. PIK3CA gene mutations were detected in three cases (8%), whereas EGFR, H-Ras, K-Ras, N-Ras and BRAF genes showed no mutations. Overall, out of 17 patients classified as FISH+, 12 cases (70%) showed a concomitant alteration in PI3K/PTEN pathway.
Conclusions:
These results provide evidence that the efficacy of anti-EGFR drugs in TN-BCBL patients could be impaired by frequent alterations in the PI3K/PTEN axis, and suggest that TN-BCBLs could benefit from tailored treatments against this axis.
Insights
Triple negative breast cancer with basal-like features (TN-BCBL) often have altered EGFR signaling. Frequent PI3K/PTEN pathway alterations in TN-BCBL may limit anti-EGFR therapy effectiveness, suggesting targeted treatments for this axis.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Triple-negative breast cancer with basal-like features (TN-BCBL) lack benefit from hormonal and anti-HER2 therapies.
- Epidermal growth factor receptor (EGFR) deregulation is observed in a significant portion of TN-BCBLs.
- EGFR-targeted therapies are being explored for TN-BCBL, necessitating predictive biomarkers.
Purpose of the Study:
- To characterize alterations in the EGFR signaling pathway in TN-BCBL.
- To identify potential predictive markers for anti-EGFR therapy response in TN-BCBL.
Main Methods:
- Morphological and immunophenotypic analysis identified 38 TN-BCBL cases.
- Immunohistochemistry assessed EGFR and PTEN protein levels.
- Fluorescence in situ hybridization (FISH) evaluated EGFR gene status.
- Direct sequencing analyzed mutations in EGFR, H-Ras, K-Ras, N-Ras, BRAF, and PIK3CA genes.
Main Results:
- EGFR overexpression (76%) and loss of PTEN expression (74%) were common in TN-BCBL.
- EGFR gene copy number gain (FISH+) was found in 51% of patients.
- PIK3CA mutations occurred in 8% of cases; other tested genes were unmutated.
- 70% of FISH+ patients exhibited concurrent PI3K/PTEN pathway alterations.
Conclusions:
- Frequent alterations in the PI3K/PTEN axis can impair the efficacy of anti-EGFR drugs in TN-BCBL.
- TN-BCBL patients may benefit from tailored treatments targeting the PI3K/PTEN axis.
