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

Borgquist, Signe LU ; Jögi, Annika LU ; Ponten, Fredrik; Rydén, Lisa LU ; Brennan, Donal J. and Jirström, Karin LU (2008) In Breast Cancer Research 10(5).
Abstract
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Breast Cancer Research
volume
10
issue
5
publisher
BioMed Central
external identifiers
  • wos:000261559000016
  • scopus:59449084603
ISSN
1465-5411
DOI
10.1186/bcr2146
language
English
LU publication?
yes
id
52de5745-9734-4101-aa29-6e160c26e3c0 (old id 1305726)
date added to LUP
2009-03-23 10:04:38
date last changed
2017-11-12 03:25:02
@article{52de5745-9734-4101-aa29-6e160c26e3c0,
  abstract     = {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 &lt; 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.},
  articleno    = {R79},
  author       = {Borgquist, Signe and Jögi, Annika and Ponten, Fredrik and Rydén, Lisa and Brennan, Donal J. and Jirström, Karin},
  issn         = {1465-5411},
  language     = {eng},
  number       = {5},
  publisher    = {BioMed Central},
  series       = {Breast Cancer Research},
  title        = {Prognostic impact of tumour-specific HMG-CoA reductase expression in primary breast cancer},
  url          = {http://dx.doi.org/10.1186/bcr2146},
  volume       = {10},
  year         = {2008},
}