The role of HMGCR expression in combination therapy of simvastatin and FAC treated locally advanced breast cancer patients

Breast Dis. 2023;42(1):73-83. doi: 10.3233/BD-220021.

Abstract

Objective: Several studies have shown the role of statin added to the patient's chemotherapy regimen and the role of Hydroxymethylglutaryl-CoA Reductase (HMGCR) expression in predicting breast cancer patient outcomes. In our previous study, adding statins improved clinical and pathological responses in LABC patients. Furthermore, we planned to study statin's role as a combination to neoadjuvant chemotherapy (NAC) in treating locally advanced breast cancers on the basis of HMGCR expression. Moreover, we aimed to study the association between the patients' clinicopathological characteristics and HMGCR expression.

Methods: This study is a randomized, double-blinded, placebo-controlled trial in two health centers in Indonesia. Each patient enrolled with written informed consent and then randomized to receive either simvastatin 40 mg/day or a placebo, combined with the fluorouracil, adriamycin, and cyclophosphamide (FAC) NAC.

Results: HMGCR was associated with low staging and normal serum cholesterol in the high Ki67 level group (p = 0.042 and p = 0.021, respectively). The pre-and post-chemotherapy tumor sizes are significantly correlated in two groups (HMGCR negative expression, p = 0.000 and HMGCR moderate expression, p = 0.001) with a more considerable average decrease in tumor size compared to HMGCR strong expression group.

Conclusion: Statin therapy might work better in HMGCR-negative or low-expression tumors, although HGMCR expression is associated with better clinical parameters in our study.

Keywords: Breast neoplasms; cholesterol; hydroxymethylglutaryl-CoA reductase inhibitors.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Breast Neoplasms* / drug therapy
  • Breast Neoplasms* / genetics
  • Breast Neoplasms* / metabolism
  • Cyclophosphamide / therapeutic use
  • Doxorubicin / therapeutic use
  • Female
  • Fluorouracil / therapeutic use
  • Humans
  • Hydroxymethylglutaryl CoA Reductases / genetics
  • Hydroxymethylglutaryl CoA Reductases / metabolism
  • Hydroxymethylglutaryl CoA Reductases / therapeutic use
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors* / therapeutic use
  • Simvastatin / therapeutic use

Substances

  • Hydroxymethylglutaryl CoA Reductases
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Simvastatin
  • Doxorubicin
  • Fluorouracil
  • Cyclophosphamide
  • HMGCR protein, human