The role of simvastatin in inhibiting migration and proliferation of breast cancer cells through Rho/ROCK signaling pathway

Yulian, Erwin Danil; Ramli, Muchlis; Setiabudy, Rianto; Siregar, Nurjati Chairani; Bustami, Arleni; Dosan, Ricky

doi:10.7243/2049-7962-5-10

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“…On the other hand, the cell lines in breast cancer that were the most sensitive in statin therapy were ones with aggressive groups such as ER-negative, HER2-positive, or triple-negative [31]. Moreover, based on a previous study by Yulian et al [12], it is recommended to use simvastatin as metastases prevention therapy in patients with high cholesterol level, receptor ER/PR negative, and HER2 positive. TOP-2A expression was one of a potential factor that play a crucial role in chromosome instability and tumorigenesis which also as a direct target of anthracycline in causing DNA damage.…”

Section: Discussionmentioning

confidence: 99%

“…Research by Garwood et al confirmed that statin induces apoptosis and decreases tumor proliferation based on clinical preoperative "window-of-opportunity" trials on breast cancer [11]. Moreover, previous research by Yulian et al [12] reported that statin synergistically interacted with anti-tumor effects (antiproliferative & apoptotic induction) and a non-overlapping toxicity profile. Therefore, we designed a phase II study of conventional fluorouracil, adriamycin, and cyclophosphamide (FAC) NAC plus low-dose simvastatin in LABC patients, to evaluate the role of statin in breast cancer, especially the combination with doxorubicin in LABC patients.…”

Section: Introductionmentioning

confidence: 94%

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Combination of Simvastatin and FAC Improves Response to Neoadjuvant Chemotherapy in Locally Advanced Breast Cancer

Yulian

Siregar

Bajuadji³

2021

Cancer Res Treat

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Purpose The efficacy of neoadjuvant chemotherapy for locally advanced breast cancer (LABC) is limited due to drug resistance and cardiotoxic effects. Preclinical studies have shown that statin induces apoptosis and decreases breast cancer cell growth. This study aims to evaluate the role of statin in combination with fluorouracil, adriamycin, and cyclophosphamide (FAC) therapy in LABC patients.Materials and Methods We undertook a randomized, double-blinded, placebo-controlled trial in two centers of Indonesia. Patients were randomly assigned to FAC plus simvastatin (40 mg/day orally) or FAC plus placebo (40 mg/day) for 21 days. The FAC regimen was repeated every 3 weeks. We evaluated the clinical response, pathological response, and toxicities.Results The objective response rate (ORR) for FAC plus simvastatin was 90% (95% confidence interval [CI], 0.99 to 1.67) by per-protocol analysis. No complete responses (CR) were recorded, but there were 48 partial responses. No significant difference was observed between the two groups with the ORR (p=0.103). The pathological CR rate was 6.25% (2 in simvastatin group and 1 in placebo group). Adverse events in both arms were generally mild, mainly consisted of myotoxicity. Human epidermal growth factor receptor 2 (HER2) expression was a factor related to the success of therapeutic response (odds ratio, 4.2; 95% CI, 1.121 to 15.731; p=0.033).Conclusion This study suggests that simvastatin combined with FAC shows improvements in ORR and pathological response in patients with LABC. Although no statistically significant difference was documented, there was a trend for better activity and tolerability. The addition of 40 mg simvastatin may improve the efficacy of FAC in LABC patients with HER2 overexpression.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 94%