Clinical validation of the suppressive impact of letrozole on liver fibrosis in patients with breast cancer undergoing continuous letrozole administration: A retrospective study

PLoS One. 2024 Oct 24;19(10):e0311930. doi: 10.1371/journal.pone.0311930. eCollection 2024.

Abstract

Treatment strategies for preventing liver fibrosis have not yet been established. Letrozole, widely used for breast cancer, has recently been reported to suppress liver fibrosis in murine models. Therefore, we aimed to validate the suppressive effects of letrozole on liver fibrosis in the clinical setting. From 2006 to 2020, 23 consecutive patients who received continuous letrozole treatment for 24 months or more and had a liver fibrosis marker FIB-4 index of ≥ 2.30, were included. Forty-three patients who underwent anastrozole treatment for 24 months or more and had a liver fibrosis marker FIB-4 index of ≥ 2.30, were also included as controls. The Fisher exact, chi-square, unpaired Student t, and paired Student t test were used to analyze the data. The patient characteristics were similar between the letrozole- and anastrozole-treated patient groups. Among the letrozole-treated patients, the mean FIB-4 index tended to decline during letrozole treatment; a significant decrease was observed at 18 and 24 months compared with the baseline values (p = 0.044 and p = 0.013). In addition, the mean aspartate aminotransferase-to-platelet ratio index (APRI) decreased during letrozole treatment; the values at 18 and 24 months were significantly lower than those at baseline (p = 0.024 and p = 0.026). In contrast, among anastrozole-treated patients, the mean FIB-4 index and APRI did not change during anastrozole treatment. When changes in the FIB-4 index were further examined in a limited number of patients with a FIB-4 index ≥ 2.67, a significant reduction in the FIB-4 index at 24 months compared with baseline was also observed in letrozole-treated patients (p = 0.023), but not in anastrozole-treated patients. In conclusion, our findings support a possible suppressive effect of letrozole on liver fibrosis in the clinical setting. Further studies are required to better understand the pharmacological effects of letrozole.

MeSH terms

  • Adult
  • Aged
  • Anastrozole / administration & dosage
  • Anastrozole / therapeutic use
  • Breast Neoplasms* / drug therapy
  • Breast Neoplasms* / pathology
  • Female
  • Humans
  • Letrozole* / administration & dosage
  • Letrozole* / therapeutic use
  • Liver Cirrhosis* / drug therapy
  • Liver Cirrhosis* / pathology
  • Middle Aged
  • Retrospective Studies

Substances

  • Letrozole
  • Anastrozole

Grants and funding

This study was supported with a research fund from Towa Pharmaceutical Co., Ltd. The funder provided support in the form of salaries for authors, Enomoto H and Tachiki H, who were employees of this company, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the "author contributions" section. There was no additional external funding received for this study.