71P - Statin-induced anti-proliferative effects via cyclin D1 and p27 in a window-of-opportunity breast cancer trial

Date 08 May 2014
Event IMPAKT 2014
Session Welcome reception and Poster Walk
Topics Breast Cancer
Translational Research
Presenter Maria Feldt
Citation Annals of Oncology (2014) 25 (suppl_1): i25-i27. 10.1093/annonc/mdu071
Authors M. Feldt1, O. Bjarnadottir1, P. Bendahl1, K. Jirström2, D. Grabau2, I. Hedenfalk1, S. Borgquist3
  • 1Department Of Clinical Sciences, Lund University, Division of Oncology, Clinical Sciences, 222 42 - Lund/SE
  • 2Department Of Clinical Sciences, Lund University, Division of Pathology, Lund University, Sweden, 222 42 - Lund/SE
  • 3Dept. Of Oncology, Skane University Hospital, 222 42 - Lund/SE



Cholesterol lowering statins have been demonstrated to exert anti-tumoral effects on breast cancer by decreasing proliferation in terms of Ki67. The biological mechanisms behind the anti-proliferative effects are currently not clear. The aim of this study was to investigate potential statin-induced effects on central cell cycle regulators, such as cyclin D1 and p27.

Experimental design:

This phase II window-of-opportunity trial included 50 patients with primary invasive breast cancer. High-dose atorvastatin (i.e., 80 mg/day) was prescribed to patients for two weeks prior to surgery. Paraffin embedded pre- and post-statin paired tumor samples were analyzed for immunohistochemical expression of the cell cycle regulators cyclin D1 and p27. Corresponding frozen tumor sample pairs were analyzed for gene expression of proliferation associated genes.


Fifty patients entered the study with forty-two patients completing all study parts. In paired tumor samples cyclin D1 expression in terms of nucleus intensity was significantly decreased (P = 0.008) after statin treatment. As for p27 the fraction of stained tumor cells increased significantly (P = 0.03) in concordance with an increase in the cytoplasmic intensity (P = 0.01). Gene expression of cyclin D1 decreased significantly following statin treatment (P < 0.0001), whereas no significant change in p27 gene expression was detected.


We have previously reported statin-induced anti-proliferative effects in breast cancer. This study suggests that the biological mechanism for the anti-proliferative effects is driven by cell cycle regulatory effects via cyclin D1 and p27. Further studies addressing the anti-tumoral effects of statins are warranted.


All authors have declared no conflicts of interest.