Introduction: Breast cancer is the most common cancer among women and more than 90% of cancer deaths are caused by metastasis. Recent studies have revealed Rho/ROCK pathway’s critical role in regulation of cancer cell migration and proliferation. Besides reducing cholesterol biosynthesis which is implicated in cancer metabolism, statins also decrease the formation of isoprenoids intermediates essential for mediating Rho/ROCK signalling. This study aimed to determine the antimetastasis (migration) effect of simvastatin on breast cancer through Rho/ROCK pathway. Method: In a randomized, double-blinded, placebo-controlled, perioperative “window” trial conducted from November 2014 until July 2015, thirty breast cancer subjects were treated with simvastatin 40 mg/day or placebo for 4–6 weeks followed by mastectomy (n = 15 in each arm) at multiple hospitals in Jakarta. Changes in migration index, ROCK activity and mRNA RhoC expression were compared between the preintervention biopsy specimen with postintervention surgical tissue. The relationships of significant factors with total cholesterol, grade, ER/PR and HER-2 status were analyzed Result: Simvastatin 40 mg/d significantly reduced migration index (p =0.006) and ROCK activity (p =0.002). A decreasing trend was observed regarding mRNA RhoC expression (p = 0.163). Reduced ROCK activity was significant among subgroups with hypercholesterolemia (p = 0.008), HER-2 amplification (p = 0.009) and low grade (p = 0.019), while it was not significantly affected by hormonal receptor expression. Conclusion: Oral simvastatin inhibits cancer migration and causes biomolecular changes within Rho/ROCK pathway in breast cancer patients, particularly in subgroups with hypercholesterolemia, HER-2 amplification and low grade.
- Breast cancer