title: Tumor-specific expression of HMG-CoA reductase in a population-based cohort of breast cancer patients.
abstract: BACKGROUND
  The mevalonate pathway synthetizes cholesterol, steroid hormones, and non-steriod isoprenoids necessary for cell survival. 3-Hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) is the rate-limiting enzyme of the mevalonate pathway and the target for statin treatment. HMGCR expression in breast tumors has recently been proposed to hold prognostic and treatment-predictive information. This study aimed to investigate whether HMGCR expression in breast cancer patients was associated with patient and tumor characteristics and disease-free survival (DFS).
  
  
  METHODS
  A population-based cohort of primary breast cancer patients in Lund, Sweden was assembled between October 2002 and June 2012 enrolling 1,116 patients. Tumor tissue microarrays were constructed and stained with a polyclonal HMGCR antibody (Cat. No HPA008338, Atlas Antibodies AB, Stockholm, Sweden, diluted 1:100) to assess the HMGCR expression in tumor tissue from 885 patients. HMGCR expression was analyzed in relation to patient- and tumor characteristics and disease-free survival (DFS) with last follow-up June 30(th) 2014.
  
  
  RESULTS
  Moderate/strong HMGCR expression was associated with less axillary lymph node involvement, lower histological grade, estrogen and progesterone receptor positivity, HER2 negativity, and older patient age at diagnosis compared to weak or no HMGCR expression. Patients were followed for up to 11 years. The median follow-up time was 5.0 years for the 739 patients who were alive and still at risk at the last follow-up. HMGCR expression was not associated with DFS.
  
  
  CONCLUSIONS
  In this study, HMGCR expression was associated with less aggressive tumor characteristics. However, no association between HMGCR expression and DFS was observed. Longer follow-up may be needed to evaluate HMGCR as prognostic or predictive marker in breast cancer.
authors.affiliation: Division of Oncology and Pathology, Department of Clinical Sciences, Lund, Lund University, Barngatan 2B, SE 22185 Lund, Sweden.
authors.forename: Emma
authors.initials: E
authors.lastname: Gustbée
authors.affiliation: Division of Oncology and Pathology, Department of Clinical Sciences, Lund, Lund University, Barngatan 2B, SE 22185 Lund, Sweden ; Department of Oncology, Skåne University Hospital, Lund, Sweden.
authors.forename: Helga
authors.initials: H
authors.lastname: Tryggvadottir
authors.affiliation: Division of Oncology and Pathology, Department of Clinical Sciences, Lund, Lund University, Barngatan 2B, SE 22185 Lund, Sweden.
authors.forename: Andrea
authors.initials: A
authors.lastname: Markkula
authors.affiliation: Division of Oncology and Pathology, Department of Clinical Sciences, Lund, Lund University, Barngatan 2B, SE 22185 Lund, Sweden.
authors.forename: Maria
authors.initials: M
authors.lastname: Simonsson
authors.affiliation: Division of Oncology and Pathology, Department of Clinical Sciences, Lund, Lund University, Barngatan 2B, SE 22185 Lund, Sweden.
authors.forename: Björn
authors.initials: B
authors.lastname: Nodin
authors.affiliation: Division of Oncology and Pathology, Department of Clinical Sciences, Lund, Lund University, Barngatan 2B, SE 22185 Lund, Sweden.
authors.forename: Karin
authors.initials: K
authors.lastname: Jirström
authors.affiliation: CREATE Health and Department of Immunotechnology, Lund University, Medicon Village, Building 406, Lund, Sweden.
authors.forename: Carsten
authors.initials: C
authors.lastname: Rose
authors.affiliation: Department of Clinical Sciences, Division of Surgery, Lund, Lund University, Lund, Sweden and Skåne University Hospital, Lund, Sweden.
authors.forename: Christian
authors.initials: C
authors.lastname: Ingvar
authors.affiliation: Division of Oncology and Pathology, Department of Clinical Sciences, Lund, Lund University, Barngatan 2B, SE 22185 Lund, Sweden ; Department of Oncology, Skåne University Hospital, Lund, Sweden.
authors.forename: Signe
authors.initials: S
authors.lastname: Borgquist
authors.affiliation: Division of Oncology and Pathology, Department of Clinical Sciences, Lund, Lund University, Barngatan 2B, SE 22185 Lund, Sweden.
authors.forename: Helena
authors.initials: H
authors.lastname: Jernström
keywords: Breast cancer; Early breast cancer events; HMG-CoA reductase; Prognosis; Treatment; Tumor characteristics