Phase II Study of Simvastatin in Primary Breast Cancer; Test of Its Potential Selectivity on Basal Subtype Breast Cancer

Summary

We hypothesize that Simvastatin administration would result in selective killing of the basal subtype of breast cancer, in particular, CD44+/CD24- breast cancer cells in primary tumor. We further hypothesize that tumor genomic changes would correlate with tumor response to Simvastatin. We are also looking to correlate Simvastatin biological effects with the expression pattern of initial status of primary tumor. In addition, we hypothesize that Simvastatin-induced tumor gene expression changes may correlate with tumor and plasma proteomics, peripheral blood mononuclear cell gene expression changes, and pharmacogenetics, and that these analyses may further refine the selection of patients most likely to benefit from Simvastatin.

Timeline

Start

2008-03

Primary completion

2014-12

Completion

2014-12

Publications

• Background Kumar AS, Benz CC, Shim V, Minami CA, Moore DH, Esserman LJ. Estrogen receptor-negative breast cancer is less likely to arise among lipophilic statin users. Cancer Epidemiol Biomarkers Prev. 2008 May;17(5):1028-33. doi: 10.1158/1055-9965.EPI-07-0726. Epub 2008 May 7.
• Background Campbell MJ, Esserman LJ, Zhou Y, Shoemaker M, Lobo M, Borman E, Baehner F, Kumar AS, Adduci K, Marx C, Petricoin EF, Liotta LA, Winters M, Benz S, Benz CC. Breast cancer growth prevention by statins. Cancer Res. 2006 Sep 1;66(17):8707-14. doi: 10.1158/0008-5472.CAN-05-4061.
• Wang T, Seah S, Loh X, Chan CW, Hartman M, Goh BC, Lee SC. Simvastatin-induced breast cancer cell death and deactivation of PI3K/Akt and MAPK/ERK signalling are reversed by metabolic products of the mevalonate pathway. Oncotarget. 2016 Jan 19;7(3):2532-44. doi: 10.18632/oncotarget.6304.

Drugs

Indications