Association between genetic polymorphisms in cytochrome P450 enzymes and survivals in women with breast cancer receiving adjuvant endocrine therapy: a systematic review and meta-analysis

Expert Rev Mol Med. 2022 Jan 7:24:e1. doi: 10.1017/erm.2021.28.

Abstract

Tamoxifen is commonly prescribed for preventing recurrence in patients with breast cancer. However, the responses of the patients on tamoxifen treatment are variable. Cytochrome P450 genetic variants have been reported to have a significant impact on the clinical outcomes of tamoxifen treatment but no tangible conclusion can be made up till now. The present review attempts to provide a comprehensive review on the associative relationship between genetic polymorphisms in cytochrome P450 enzymes and survival in breast cancer patients on adjuvant tamoxifen therapy. The literature search was conducted using five databases, resulting in the inclusion of 58 studies in the review. An appraisal of the reporting quality of the included studies was conducted using the assessment tool from the Effective Public Health Practice Project (EPHPP). Meta-analyses were performed on CYP2D6 studies using Review Manager 5.3 software. For other studies, descriptive analyses were performed. The results of meta-analyses demonstrated that shorter overall survival, disease-free survival and relapse-free survival were found in the patients with decreased metabolisers when compared to normal metabolisers. The findings also showed that varying and conflicting results were reported by the included studies. The possible explanations for the variable results are discussed in this review.

Keywords: Adjuvant endocrine therapy; breast cancer; cytochrome P450; genetic polymorphism; genotype; survival; tamoxifen.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Antineoplastic Agents, Hormonal / therapeutic use
  • Breast Neoplasms* / drug therapy
  • Breast Neoplasms* / genetics
  • Cytochrome P-450 Enzyme System / genetics
  • Cytochrome P-450 Enzyme System / therapeutic use
  • Female
  • Genotype
  • Humans
  • Neoplasm Recurrence, Local / genetics
  • Polymorphism, Genetic
  • Tamoxifen / therapeutic use

Substances

  • Antineoplastic Agents, Hormonal
  • Tamoxifen
  • Cytochrome P-450 Enzyme System