Prognostic impact of tumour-specific HMG-CoA reductase expression in primary breast cancer.
BACKGROUND
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.
Borgquist
Signe
S
Center for Molecular Pathology, Department of Laboratory Medicine, Malmö University Hospital, Lund University, Malmö, Sweden.
Jögi
Annika
A
Pontén
Fredrik
F
Rydén
Lisa
L
Brennan
Donal J
DJ
Jirström
Karin
K
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000201:enzymology* / Q000401:mortality / Q000628:therapy; D002277:Carcinoma / Q000201:enzymology* / Q000401:mortality / Q000628:therapy; D017024:Chemotherapy, Adjuvant; D015331:Cohort Studies; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000032:analysis*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis*; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D011960:Receptors, Estrogen / Q000032:analysis; D013629:Tamoxifen / Q000627:therapeutic use
D018931:Antineoplastic Agents, Hormonal; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D009363:Neoplasm Proteins; D011960:Receptors, Estrogen; D013629:Tamoxifen; D006903:Hydroxymethylglutaryl CoA Reductases