PTEN rs701848 Polymorphism is Associated with Trastuzumab Resistance in HER2-positive Metastatic Breast Cancer and Predicts Progression-free Survival

Clin Breast Cancer. 2023 Apr;23(3):e131-e139. doi: 10.1016/j.clbc.2022.12.010. Epub 2022 Dec 20.

Abstract

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 predicting 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.

Keywords: Breast cancer, PTEN rs701848, Trastuzumab, Survival; HER2-positive.

MeSH terms

  • Breast Neoplasms* / drug therapy
  • Breast Neoplasms* / genetics
  • Breast Neoplasms* / pathology
  • Case-Control Studies
  • Female
  • Humans
  • PTEN Phosphohydrolase / genetics
  • PTEN Phosphohydrolase / therapeutic use
  • Progression-Free Survival
  • Receptor, ErbB-2 / genetics
  • Receptor, ErbB-2 / therapeutic use
  • Trastuzumab / therapeutic use

Substances

  • Trastuzumab
  • Receptor, ErbB-2
  • PTEN Phosphohydrolase
  • PTEN protein, human