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

Abstract

Abstract Abstract #5071 Background
 We have previously reported that tumour-specific expression of the rate-limiting enzyme in the mevalonate pathway, 3-hydroxy-3-methylglutharyl-coenzyme A reductase (HMG-CoAR) 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 (IHC) on tissue microarrays with tumour specimens from 498 consecutive breast cancer cases with a median follow-up of 128 months. Kaplan Meier analysis and Cox proportional hazards modelling were used to estimate the risk of recurrence free and breast cancer specific survival.
 Results 
 In line with our previous findings, tumour-specific HMG-CoAR expression was associated with, low grade (p <0.001), small (p = 0.007), ERα positive (p =0.01), Ki-67 negative (p =0.02) tumors. Patients with tumours expressing HMG-CoAR, had a significantly prolonged disease-free-survival, also when adjusted for established prognostic factors; RR= 0.60, 95% CI (0.40-0.92); p=0.02. In estrogen receptor negative tumours, however, there was a trend, however non-significant, towards a shorter DFS in HMG-CoAR expressing tumours.
 Conclusion
 HMG-CoAR expression is an independent predictor of a prolonged disease-free-survival in primary breast cancer. This may, however, not be true for ERα 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. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5071.