Her2/EGFR-PDGFR pathway aberrations associated with tamoxifen response in metastatic breast cancer patients
Ibrahim Malash1, Osman Mansour1, Rabab Gaafar1
1Medical Oncology Department, National Cancer Institute (NCI), Cairo University, Cairo, 11976, Egypt.
Background:
Metastatic breast cancer (MBC) is a major health problem worldwide. Some patients improve on tamoxifen and others do not respond to treatment. Therefore, the aim of the current study is to assess genetic aberrations in the Her2/EGFR-PDGFR pathway associated with tamoxifen response in MBC patients.
Methods:
This is a retrospective cohort study, including 157 hormone receptors positive, locally recurrent inoperable and/or MBC patients on tamoxifen treatment. Patients were categorized into 78 (49.7%) tamoxifen responders and 79 (50.3%) tamoxifen non-responder patients. Genetic aberrations of 84 genes involved in the Her2/EGFR-PDGFR pathway were assessed in the tumor tissue samples obtained from the patients using SA-Bioscience assay. The identified panel was correlated to patients' response to treatment, to detect the differentially expressed genes in tamoxifen responders and non-responders.
Results:
One hundred twenty-three (78.3%) patients were estrogen receptor (ER) and progesterone receptor (PR) positive, 108 (68.8%) were ER only positive, and 78 (49.7%) were PR only positive. There were 56 genes overexpressed in the refractory group compared to responders. However, only five out of these 56 genes, Janus kinase 1 (JAK1), collagen type I alpha 1 (COL1A1), GRB2-associated binding protein 1 (GAB1), fibronectin-1 (FN1), and MAP kinase-interacting serine/threonine-protein kinase (MKNK1), showed statistical significance between the two groups. Patients with bone metastasis showed a better response to treatment compared to those with metastatic deposits in other sites such as visceral metastasis (P < 0.005).
Conclusions:
Genetic profiling using simple quantitative real-time polymerase chain reaction (qRT-PCR) protocols could be used to assess response to tamoxifen treatment in MBC patients. According to our data, a five-gene panel in the EGFR pathway (JAK1, COL1A1, GAB1, FN1 and MKNK1) could be used to categorize MBC patients into groups according to treatment response.
Insights
A five-gene panel (JAK1, COL1A1, GAB1, FN1, MKNK1) in the Her2/EGFR-PDGFR pathway can predict tamoxifen response in metastatic breast cancer (MBC) patients. This genetic profiling offers a potential method for personalizing MBC treatment strategies.
Area of Science:
- Oncology
- Genetics
- Pharmacogenomics
Background:
- Metastatic breast cancer (MBC) presents a significant global health challenge.
- Tamoxifen response varies among MBC patients, necessitating predictive biomarkers.
- Investigating genetic aberrations in the Her2/EGFR-PDGFR pathway is crucial for understanding tamoxifen resistance.
Purpose of the Study:
- To assess genetic aberrations in the Her2/EGFR-PDGFR pathway associated with tamoxifen response in MBC patients.
- To identify specific genes that correlate with treatment outcomes in MBC.
- To explore the potential of genetic profiling for predicting tamoxifen efficacy.
Main Methods:
- Retrospective cohort study of 157 hormone receptor-positive MBC patients treated with tamoxifen.
- Categorization of patients into tamoxifen responders (49.7%) and non-responders (50.3%).
- Assessment of genetic aberrations in 84 pathway genes using SA-Bioscience assay and correlation with treatment response.
Main Results:
- Five statistically significant genes (JAK1, COL1A1, GAB1, FN1, MKNK1) were identified as differentially expressed between responders and non-responders.
- Overexpression of 56 genes was observed in the non-responder group compared to responders.
- Patients with bone metastasis demonstrated a better response to tamoxifen than those with visceral metastasis.
Conclusions:
- Quantitative real-time polymerase chain reaction (qRT-PCR) based genetic profiling can predict tamoxifen response in MBC.
- A five-gene panel (JAK1, COL1A1, GAB1, FN1, MKNK1) holds potential for categorizing MBC patients based on treatment response.
- This genetic approach may facilitate personalized treatment strategies for MBC.
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