ArticleAsian Pacific journal of cancer prevention : APJCP2024
Targeted Sequencing of HER2-Positive Breast Cancer Mutations Revealed a Potential Association between PIK3CA and Trastuzumab Resistance.
Article in Asian Pacific journal of cancer prevention : APJCP, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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2 citing papers in PubMed.
- Recent Research Advances in HER2-Positive Breast Cancer Concerning Targeted Therapy Drugs.Molecules (Basel, Switzerland) · 2025Review
- Effects of PIK3CA Gene Modifications on Radiosensitivity in Colorectal Cancer Cells.Asian Pacific journal of cancer prevention : APJCP · 2025Article
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5 authors.
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Abstract
backgroundDifferent molecular subtypes, including HER2-positive, have been identified in breast cancer. The overexpression of HER2 triggers downstream signaling pathways such as the PI3K/AKT/mTOR pathway. Until recently, trastuzumab has been used as a single HER2-targeted therapy in Egypt. However, resistance to trastuzumab has been reported. Previous studies have demonstrated the genetic variants that affect the trastuzumab response. However in Egypt, few studies investigated molecular biomarkers such as p53 that might affect the trastuzumab response. Therefore, we aimed to extend the genetics workup of Her2 + BC to include important oncogenes and other vital cancer pathways.
methodsFormalin-fixed paraffin-embedded samples were collected from 24 HER2+ BC Egyptian patients, twelve patients in complete remission for 2 years or more from the start of trastuzumab and twelve resistant patients who relapsed or developed metastasis within 2 years from the start of trastuzumab. Somatic mutations in hotspot regions of 17 genes were further investigated using next-generation sequencing.
resultsAmong the total number of identified variants (106 variants), PIK3CA showed the most frequent variants, with more variants occurring in the resistant group than in the responsive group (P= 0.004). The frequency of PIK3CA mutations was greater in resistant patients than in responsive patients (P= 0.036). Additionally, there was a significant correlation between PIK3CA mutations and pathological complete response (pCR) (P=0.036). Most of PIK3CA variants in resistant patients were detected in exon 9 and 20. The PIK3CA variants His1047Tyr, Glu545Lys, His701Pro, Lys111Glu, Val344Gly and Tyr1021Cys were found only in the resistant patients, suggesting that they are associated with trastuzumab resistance.
conclusionPIK3CA variants were more frequent in resistant HER2+ BC patients than in responsive patients, with a significant correlation between PIK3CA mutation and a lower pCR rate. PIK3CA variants within exon 9 and 20 (such as Glu545Lys and His1047Tyr respectively) were associated with trastuzumab resistance.
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