El-Khazragy, NashwaGaballah, AhmedBakkar, AshrafHemida, Eman H.ASamir, NehalTarek, MarwaAdly, Heba MSaleh, Saleh A.KHanna, Demiana H2023-01-282023-01-282023-01https://doi.org/10.1016/j.clbc.2022.12.010https://tinyurl.com/2ewjxlxwThe high mortality rate of HER-2+ve breast cancer (BC) is linked to Trastuzumab resistance, which is linked to PTEN rs701848 variants. In 160 patients with metastatic HER2+ve BC who were treated with trastuzumab, the PTEN genotypes were determined. Obtained results revealed that the PTEN locus is a major predictor of Trastuzumab resistance, and the C allele is linked to a higher risk. Background: Trastuzumab is an effective therapeutic approach for HER2-positive metastatic breast cancer (BC). However, a considerable number of patients develop resistance along the course of the disease. PTEN rs701848 polymorphisms are associated with an increased risk of developing cancer and have a potential role in predict- ing drug resistance. Objective: We studied the significance of PTEN rs701848 variants as significant predictors for trastuzumab resistance in HER2-positive metastatic BC patients. Therefore, considering their value in predicting clinical outcomes. Materials and Methods: This case-control study was conducted among female patients with HER2-positive metastatic breast cancer who underwent Trastuzumab therapy during the period from March 2017 to December 2020. PTEN rs701848 genotypes were analyzed in 160 HER2-positive metastatic breast cancer who received Trastuzumab therapy and clinically monitored for therapeutic response. Results: PTEN rs701848 is deemed a significant predictor of Trastuzumab resistance and an independent prognostic factor of progression-free survival (PPFS). In particular, the C allele is associated with increased risk for Trastuzumab resistance and shorter PFS as compared to the homozygous TT genotype. Conclusion: PTEN rs701848 is significant predictor of trastuzumab resistance. Therefore, their value in predicting clinical outcomes is recommended Clinical Breast Cancer, Vol. 000, No.xxx, 1–9 © 2022 Elsevier Inc. All rights reserved.en-USHER2-positive,Breast cancer,PTEN rs701848,Trastuzumab,SurvivalArticlehttps://doi.org/10.1016/j.clbc.2022.12.010