BACKGROUND: Patients with ductal carcinoma-in-situ (DCIS) are currently not 
prescribed adjuvant systemic treatment after surgery and radiotherapy. 
Prediction of DCIS patients who would benefit from radiotherapy is warranted. 
Statins have been suggested to exert radio-sensitizing effects. The target for 
cholesterol-lowering statins is HMG-CoA reductase (HMGCR), the rate-limiting 
enzyme in the mevalonate pathway. The aim of this study was to examine HMGCR 
expression in DCIS and study its treatment predictive value.
METHODS: A population-based cohort including 458 women diagnosed with primary 
DCIS between 1986 and 2004 were followed until November 2011 to study long-term 
survival. Tumor tissue microarrays were constructed, and immunohistochemical 
analyses were performed to detect cytoplasmic protein expression of HMGCR. The 
association between DCIS HMGCR expression and invasive breast cancer 
recurrence-free survival (RFSinv) and overall survival (OS) was analyzed by 
Kaplan-Meier curves, log rank test, and Cox proportional hazard analysis.
RESULTS: HMGCR was strongly expressed in 24 % of the assessed DCIS samples, 
moderately expressed in 46 %, and weakly expressed in 23 %; no expression was 
detected in 7 % of the samples. During the follow-up time (median 13.8 years), 
61 patients were diagnosed with an invasive breast cancer recurrence, and 80 
patients died. A crude analysis showed no survival benefit from radiotherapy. 
However, patients with strong HMGCR expression showed an improved RFSinv (log 
rank, p = 0.03) and OS (log rank, p = 0.04) after radiotherapy. No statistically 
significant interaction was observed for HMGCR and radiotherapy (RFSinv p = 0.69 
and OS p = 0.29).
CONCLUSIONS: This study demonstrates HMGCR expression in DCIS and suggests HMGCR 
as a predictive marker of response to postoperative radiotherapy in DCIS, 
although the test for interaction was nonsignificant. Future DCIS studies 
addressing the potential of statin treatment targeting HMGCR are warranted.