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.
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.
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.
PTEN rs701848 is significant predictor of trastuzumab resistance. Therefore, their value in predicting clinical outcomes is recommended
Abbreviations:PR (partial remission), SD (stable disease), PD (progressive disease), OS (overall survival), PFS (progression-free survival), OR (odds ratio), HR (hazards ratio), CI (confidence interval), BC (breast cancer), BMI (body mass index), LN (lymph node), PR (progesterone receptors), ER (estrogen receptors)
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- Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.CA: Cancer J Clin. 2021; 71: 209-249
- Her2/EGFR-PDGFR pathway aberrations associated with tamoxifen response in metastatic breast cancer patients.J Egypt Natl Cancer Inst. 2022; 34: 31
- Frequency and clinical features of over-expressed HER2 in Egyptian breast cancer women patients %j the Egyptian journal of hospital medicine.Egyptian J Hosp Med. 2021; 85: 3431-3435
- Targeted therapeutic options and future perspectives for HER2-positive breast cancer.Signal Transdt Target Ther. 2019; 4: 34
- The assessment of HER2 status in breast cancer: the past, the present, and the future.Pathol Int. 2016; 66: 313-324
- US incidence of breast cancer subtypes defined by joint hormone receptor and HER2 status.J Natl Cancer Inst. 2014; 106
- Current and future management of her2-positive metastatic breast cancer.JCO Oncol Pract. 2021; 17: 594-604
- Evolving standards of care and new challenges in the management of HER2-positive breast cancer.CA Cancer J Clin. 2020; 70: 355-374
- Breast cancer characteristics in very young Egyptian women ≤35 years.Breast cancer (Dove Medical Press). 2016; 8: 53-58
- Association of genetic polymorphisms in PTEN and additional gene-gene interaction with risk of esophageal squamous cell carcinoma in Chinese Han population.Dis Esophagus. 2016; 29: 944-949
- Association of single nucleotide polymorphisms (SNPs) with gastric cancer susceptibility and prognosis in population in Wuwei, Gansu, China.World J Surg Oncol. 2022; 20: 194
- Single nucleotide polymorphisms and cancer susceptibility.Oncotarget. 2017; 8: 110635-110649
- Prognostic and predictive implications of PTEN in breast cancer: unfulfilled promises but intriguing perspectives.Cancers. 2019; 11: 1401
- PTEN as a prognostic/predictive biomarker in cancer: an unfulfilled promise?.Cancers. 2019; 11: 435
- HER2-positive breast cancer and tyrosine kinase inhibitors: the time is now.npj Breast Cancer. 2021; 7: 56
- HER2 and Breast Cancer — a Phenomenal Success Story.N Engl J Med. 2019; 381: 1284-1286
- Overview of genetic signaling pathway interactions within cutaneous malignancies.J Cancer Metast Treat. 2020; 6: 37
- Drug resistance and combating drug resistance in cancer.Cancer Drug Resist. 2019; 2: 141-160
- Anti-HER2 therapy in metastatic breast cancer: many choices and future directions.Cancer Metastasis Rev. 2022; 41: 193-209
- Development and clinical application of anti-HER2 monoclonal and bispecific antibodies for cancer treatment.Exp Hematol Oncol. 2017; 6: 31
- Trastuzumab emtansine versus taxane use for previously treated HER2-positive locally advanced or metastatic gastric or gastro-oesophageal junction adenocarcinoma (GATSBY): an international randomised, open-label, adaptive, phase 2/3 study.Lancet Oncol. 2017; 18: 640-653
- Trastuzumab mechanism of action; 20 years of research to unravel a dilemma.Cancers. 2021; 13: 3540
- Mechanisms of resistance to trastuzumab emtansine (T-DM1) in HER2-positive breast cancer.Br J Cancer. 2020; 122: 603-612
- Resistance to anti-HER2 therapies in breast cancer.Am Soc Clin Oncol Educ Book. 2015; 35: e157-e164
- The genetic variants in the PTEN/PI3K/AKT pathway predict susceptibility and CE(A)F chemotherapy response to breast cancer and clinical outcomes.Oncotarget. 2017; 8: 20252-20265
- PTEN downregulation induces apoptosis and cell cycle arrest in uterine cervical cancer cells.Exp Ther Med. 2021; 22: 1100
- Evaluation of the association of PIK3CA mutations and PTEN loss with efficacy of trastuzumab therapy in metastatic breast cancer.Breast cancer research and treatment. 2011; 128: 447-456
- The strengthening the reporting of observational studies in epidemiology (STROBE) statement: guidelines for reporting observational studies.Int J Surg. 2014; 12: 1495-1499
- Tumor response assessment for precision cancer therapy: response evaluation criteria in solid tumors and beyond.Am Soc Clin Oncol Educ Book. 2018; 38: 1019-1029
- Human epidermal growth factor receptor 2 (her2) in cancers: overexpression and therapeutic implications.Mol Biol Int. 2014; 2014852748
- PTEN loss and level of HER2 amplification is associated with trastuzumab resistance and prognosis in HER2-positive gastric cancer.Oncotarget. 2017; 8: 113494-113501
- PTEN activation contributes to tumor inhibition by trastuzumab, and loss of PTEN predicts trastuzumab resistance in patients.Cancer cell. 2004; 6: 117-127
- PI3K-p110α mediates resistance to HER2-targeted therapy in HER2+, PTEN-deficient breast cancers.Oncogene. 2016; 35: 3607-3612
- Targeting PI3K in cancer: mechanisms and advances in clinical trials.Mol Cancer. 2019; 18: 26
- CTMP, a predictive biomarker for trastuzumab resistance in HER2-enriched breast cancer patient.Oncotarget. 2017; 8: 29699-29710
Published online: December 20, 2022
Accepted: December 17, 2022
Received in revised form: December 6, 2022
Received: September 8, 2022
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