The Role of Simvastatin in The Epithelial-Mesenchymal Transition Process of Breast Cancer
Status:
Recruiting
Trial end date:
2025-02-01
Target enrollment:
Participant gender:
Summary
Introduction: Most cases of Triple Negative Breast Cancer (TNBC) have a high proliferation
rate. TNBC is associated with a poor prognosis, a high recurrence rate, and a high incidence
of distant metastases. The Epithelial-Mesenchymal Transition process (EMT) plays an essential
role in the metastatic process. EMT markers were also more abundant in TNBC and contributed
to a poorer TNBC prognosis. As an important EMT marker, the increased expression of vimentin
also contributed to the increase in TNBC aggressiveness and resistance to chemotherapeutic
agents. Through the mechanism of action in inhibiting the mevalonate pathway, statins can
help inhibit the EMT process in metastases. Notably, simvastatin promotes the down-regulation
of vimentin in breast cancer cells. The combination of statins and neoadjuvant chemotherapy
(NAC) improves the cancer patient's response. This study is expected to evaluate the role of
a combination between NAC and simvastatin on therapeutic response in TNBC patients through
vimentin expression.
Methods: This study is a double-blind, randomized, placebo-controlled trial conducted in Dr.
Cipto Mangunkusumo National Central General Hospital. An expected total of 26 TNBC patients
will be assessed for eligibility and asked for informed consent. Patients with the plan to
have ACT (Doxorubicin hydrochloride, Cyclophosphamide, Paclitaxel) chemotherapy regimen will
receive either a combination of ACT-Simvastatin (40 mg/day) or ACT-Placebo. The biopsy will
be taken pre-NAC to make the histopathological diagnosis and examine the expression of
vimentin. Patients will be evaluated for adverse effects reaction every cycle and the
clinical response after 8 cycles. The post-intervention biopsy will be conducted after the
cycle finish. The pathological response and vimentin expression will be reviewed from the
obtained samples.