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- Title
Role of Some Estrogen Receptor and Her2 Pathway related Genes (PIK3CA, GSK3 ß) in Predicting Response to Tamoxifen in Breast Cancer Patients.
- Authors
Hassan, Yasser Arafat; Samra, Mohamed Abd EL-Motti; Bahnasy, Abeer Ahmed; Helal, Amany Mohmed; Shahin, Amgad Ahmed
- Abstract
Background: PIK3CA and GSK-3ß have important role(s) in the resistance of estrogen receptor positive (+ER) breast cancer (BC) patients to hormonal therapy. The aim of the current study was to assess the role of PIK3CA and GSK-3ß in predicting response to Tamoxifen in BC patients. Methods: PIK3CA and GSK-3ß expression levels were assessed in formalin fixed paraffin embedded tissue (FFPE) sections of 58 hormonal positive BC females, using quantitative real time PCR (RT-qPCR). The data were correlated to clinicopathological features of the patients, response to Tamoxifen and survival outcome. Results: The median PIK3CA expression increased significantly in non-responders to tamoxifen compared to responders [2.94 (IQR=7.5) and 0.72 (IQR=0.9); respectively, P= 0.017]. However, there was no significant difference in GSK-3ß expression between responders and non-responders BC patients [1.5 (IQR=3.8) and 1.2 (IQR=2.8); respectively, P= 0.27]. PIK3CA expression associated with low ER expression, presence of distant metastasis and shorter disease free survival (DFS) rate (P=0.032, 0.026 and 0.043; respectively). GSK-3ß expression increased significantly in negative LN metastasis and low-expression of progesterone receptors (P=0.01 and 0.006; respectively). There was significant correlation between the expression levels of GSK-3B and PIK3CA in BC patients (r=0.88, P<0.001), and non-responders (r=0.97, p<0.001). However, in the responders, there was a non-significant negative correlation between the two markers (r=-0.16, P=0.43). Multivariate analysis showed that tumor size and PIK3CA expression were independent prognostic factors for reduced DFS in BC patients. Conclusion: PIK3CA is a negative predictor for BC patients' outcome, and for poor response to Tamoxifen. PIK3CA and GSK-3ß could be a potential prognostic and molecular targets for breast cancer therapy.
- Subjects
TAMOXIFEN; ESTROGEN receptors; BREAST cancer treatment; HORMONE therapy; POLYMERASE chain reaction
- Publication
Zagazig University Medical Journal, 2023, Vol 29, Issue 1, p210
- ISSN
1110-1431
- Publication type
Article
- DOI
10.21608/zumj.2021.62896.2142