Mismatch repair protein deficiency in triple-negative breast carcinomas

J Int Med Res. 2024 Jun;52(6):3000605241259747. doi: 10.1177/03000605241259747.

Abstract

Background: Breast cancer, particularly triple-negative breast cancer (TNBC), poses a significant global health burden. Chemotherapy was the mainstay treatment for TNBC patients until immunotherapy was introduced. Studies indicate a noteworthy prevalence (0.2% to 18.6%) of mismatch repair protein (MMRP) deficiency in TNBC, with recent research highlighting the potential of immunotherapy for MMRP-deficient metastatic breast cancer. This study aims to identify MMRP deficiency in TNBC patients using immunohistochemistry.

Methods: A retrospective cohort study design was used and included TNBC patients treated between 2015 and 2021 at King Hussein Cancer Center. Immunohistochemistry was conducted to assess MMRP expression.

Results: Among 152 patients, 14 (9.2%) exhibited deficient MMR (dMMR). Loss of PMS2 expression was observed in 13 patients, 5 of whom showed loss of MLH1 expression. Loss of MSH6 and MSH2 expression was observed in one patient. The median follow-up duration was 44 (3-102) months. Despite the higher survival rate (80.8%, 5 years) of dMMR patients than of proficient MMR patients (62.3%), overall survival did not significantly differ between the two groups.

Conclusion: Approximately 9% of TNBC patients exhibit dMMR. dMMR could be used to predict outcomes and identify patients with TNBC who may benefit from immunotherapy.

Keywords: Triple negative; breast cancer; immunohistochemistry; immunotherapy; microsatellite instability; mismatch repair deficiency.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • DNA Mismatch Repair*
  • DNA-Binding Proteins* / genetics
  • DNA-Binding Proteins* / metabolism
  • Female
  • Humans
  • Immunohistochemistry
  • Middle Aged
  • Mismatch Repair Endonuclease PMS2* / genetics
  • Mismatch Repair Endonuclease PMS2* / metabolism
  • MutL Protein Homolog 1 / genetics
  • MutL Protein Homolog 1 / metabolism
  • MutS Homolog 2 Protein / metabolism
  • Prognosis
  • Retrospective Studies
  • Survival Rate
  • Triple Negative Breast Neoplasms* / genetics
  • Triple Negative Breast Neoplasms* / metabolism
  • Triple Negative Breast Neoplasms* / pathology

Substances

  • Mismatch Repair Endonuclease PMS2
  • PMS2 protein, human
  • DNA-Binding Proteins
  • MutL Protein Homolog 1
  • MutS Homolog 2 Protein
  • MSH2 protein, human
  • MLH1 protein, human
  • G-T mismatch-binding protein
  • Biomarkers, Tumor