Prognostic impact of tumour-specific HMG-CoA reductase expression in primary breast cancer

Breast Cancer Res. 2008;10(5):R79. doi: 10.1186/bcr2146. Epub 2008 Sep 22.


Introduction: We have previously reported that tumour-specific expression of the rate-limiting enzyme, 3-hydroxy-3-methylglutharyl-coenzyme A reductase (HMG-CoAR), in the mevalonate pathway is associated with more favourable tumour parameters in breast cancer. In the present study, we examined the prognostic value of HMG-CoAR expression in a large cohort of primary breast cancer patients with long-term follow up.

Methods: The expression of HMG-CoAR was assessed by immunohistochemistry on tissue microarrays with tumour specimens from 498 consecutive cases of breast cancer with a median follow-up of 128 months. Kaplan Meier analysis and Cox proportional hazards modelling were used to estimate the rate of recurrence-free survival (RFS) and breast cancer specific survival (BCSS).

Results: In line with our previous findings, tumour-specific HMG-CoAR expression was associated with low grade (p < 0.001), small size (p = 0.007), oestrogen receptor (ER) positive (p = 0.01), low Ki-67 (p = 0.02) tumours. Patients with tumours expressing HMG-CoAR had a significantly prolonged RFS, even when adjusted for established prognostic factors (relative risk [RR] = 0.60, 95% confidence interval [CI] 0.40 to 0.92; p = 0.02). In ER-negative tumours, however, there was a trend, that was not significantly significant, towards a shorter RFS in HMG-CoAR expressing tumours.

Conclusions: HMG-CoAR expression is an independent predictor of a prolonged RFS in primary breast cancer. This may, however, not be true for ER-negative tumours. Further studies are needed to shed light on the value of HMG-CoAR expression as a surrogate marker of response to statin treatment, especially with respect to hormone receptor status.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents, Hormonal / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Breast Neoplasms / enzymology*
  • Breast Neoplasms / mortality
  • Breast Neoplasms / therapy
  • Carcinoma / enzymology*
  • Carcinoma / mortality
  • Carcinoma / therapy
  • Chemotherapy, Adjuvant
  • Cohort Studies
  • Combined Modality Therapy
  • Disease-Free Survival
  • Female
  • Humans
  • Hydroxymethylglutaryl CoA Reductases / analysis*
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Lymphatic Metastasis
  • Middle Aged
  • Neoplasm Proteins / analysis*
  • Oligonucleotide Array Sequence Analysis
  • Prognosis
  • Receptors, Estrogen / analysis
  • Tamoxifen / therapeutic use


  • Antineoplastic Agents, Hormonal
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Neoplasm Proteins
  • Receptors, Estrogen
  • Tamoxifen
  • Hydroxymethylglutaryl CoA Reductases