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HMGCR 表达在辛伐他汀联合 FAC 局部晚期乳腺癌患者治疗中的作用。

The role of HMGCR expression in combination therapy of simvastatin and FAC treated locally advanced breast cancer patients.

机构信息

Division of Surgical Oncology, Department of Surgery, Dr. Cipto Mangunkusumo General Hospital, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia.

Department of Pathology, Dr. Cipto Mangunkusumo General Hospital, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia.

出版信息

Breast Dis. 2023;42(1):73-83. doi: 10.3233/BD-220021.

Abstract

OBJECTIVE

Several studies have shown the role of statin added to the patient's chemotherapy regimen and the role of Hydroxymethylglutaryl-CoA Reductase (HMGCR) expression in predicting breast cancer patient outcomes. In our previous study, adding statins improved clinical and pathological responses in LABC patients. Furthermore, we planned to study statin's role as a combination to neoadjuvant chemotherapy (NAC) in treating locally advanced breast cancers on the basis of HMGCR expression. Moreover, we aimed to study the association between the patients' clinicopathological characteristics and HMGCR expression.

METHODS

This study is a randomized, double-blinded, placebo-controlled trial in two health centers in Indonesia. Each patient enrolled with written informed consent and then randomized to receive either simvastatin 40 mg/day or a placebo, combined with the fluorouracil, adriamycin, and cyclophosphamide (FAC) NAC.

RESULTS

HMGCR was associated with low staging and normal serum cholesterol in the high Ki67 level group (p = 0.042 and p = 0.021, respectively). The pre-and post-chemotherapy tumor sizes are significantly correlated in two groups (HMGCR negative expression, p = 0.000 and HMGCR moderate expression, p = 0.001) with a more considerable average decrease in tumor size compared to HMGCR strong expression group.

CONCLUSION

Statin therapy might work better in HMGCR-negative or low-expression tumors, although HGMCR expression is associated with better clinical parameters in our study.

摘要

目的

多项研究表明,在患者的化疗方案中加入他汀类药物以及羟甲基戊二酰辅酶 A 还原酶 (HMGCR) 表达的作用可预测乳腺癌患者的结局。在我们之前的研究中,添加他汀类药物改善了局部晚期乳腺癌(LABC)患者的临床和病理反应。此外,我们计划根据 HMGCR 表达,研究他汀类药物作为联合新辅助化疗(NAC)治疗局部晚期乳腺癌的作用。此外,我们旨在研究患者的临床病理特征与 HMGCR 表达之间的关联。

方法

这是在印度尼西亚的两个医疗中心进行的一项随机、双盲、安慰剂对照试验。每位入组患者均签署书面知情同意书,然后随机接受辛伐他汀 40mg/天或安慰剂,联合氟尿嘧啶、阿霉素和环磷酰胺(FAC)NAC。

结果

HMGCR 与高 Ki67 水平组的低分期和正常血清胆固醇相关(p=0.042 和 p=0.021)。两组化疗前后的肿瘤大小均显著相关(HMGCR 阴性表达,p=0.000 和 HMGCR 中度表达,p=0.001),与 HMGCR 强表达组相比,肿瘤大小的平均下降更为显著。

结论

尽管在我们的研究中 HGMCR 表达与更好的临床参数相关,但他汀类药物治疗可能在 HMGCR 阴性或低表达肿瘤中效果更好。

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