Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
Department of Medical Oncology, Cancer Hospital of HuanXing ChaoYang District Beijing, 100005, China.
Breast. 2020 Aug;52:17-22. doi: 10.1016/j.breast.2020.04.004. Epub 2020 Apr 16.
We performed a retrospective study on the efficacy and safety of sirolimus (an mTOR inhibitor) in hormone receptor (HR)-positive advanced breast cancer and searched for biomarkers to predict its efficacy.
All patients with HR-positive metastatic breast cancer treated with sirolimus plus endocrine therapy between December 2017 and July 2018 at the Cancer Hospital, Chinese Academy of Medical Sciences were consecutively and retrospectively reviewed. Mutations in circulating tumour DNA (ctDNA) were assayed for 1021 tumour-related genes via gene panel target capture-based next-generation sequencing.
Thirty-six patients with metastatic breast cancer treated with sirolimus plus endocrine therapy were included. The progression-free survival (PFS) rates between the sirolimus group and everolimus group were similar, and the median PFS was 4.9 months and 5.5 months, respectively (hazard ratio 1.56, 95% CI 0.86-2.81, P = 0.142). The objective response rate in the 36 patients was 19.4%, and the clinical benefit rate was 41.7%. Lipid metabolism disorder was the most common adverse event (69.4%), and 13.9% of patients had stomatitis. Most (94.4%) adverse events were grade 1-2. Twenty patients (55.6%) underwent ctDNA analysis before receiving sirolimus therapy. For patients who received less than 3 lines of chemotherapy, those with PI3K/Akt/mTOR pathway alterations had a better response to sirolimus than those without alterations, with a median PFS of 7.0 months vs 4.3 months (hazard ratio = 0.01, 95% CI 0.00-0.34, P = 0.010).
Sirolimus is a potentially effective treatment option for patients with HR-positive advanced breast cancer.
我们对 mTOR 抑制剂西罗莫司（sirolimus）治疗激素受体（HR）阳性晚期乳腺癌的疗效和安全性进行了回顾性研究，并寻找预测其疗效的生物标志物。
回顾性分析 2017 年 12 月至 2018 年 7 月在中国医学科学院肿瘤医院接受西罗莫司联合内分泌治疗的 HR 阳性转移性乳腺癌患者。采用基于基因panel 目标捕获的下一代测序技术，对 1021 个肿瘤相关基因的循环肿瘤 DNA（ctDNA）进行突变分析。
共纳入 36 例接受西罗莫司联合内分泌治疗的转移性乳腺癌患者。西罗莫司组和依维莫司组的无进展生存期（PFS）率相似，中位 PFS 分别为 4.9 个月和 5.5 个月（风险比 1.56，95%CI 0.86-2.81，P=0.142）。36 例患者的客观缓解率为 19.4%，临床获益率为 41.7%。脂代谢紊乱是最常见的不良事件（69.4%），13.9%的患者发生口腔炎。大多数（94.4%）不良事件为 1-2 级。20 例（55.6%）患者在接受西罗莫司治疗前进行了 ctDNA 分析。对于接受少于 3 线化疗的患者，PI3K/Akt/mTOR 通路改变的患者对西罗莫司的反应优于无改变的患者，中位 PFS 分别为 7.0 个月和 4.3 个月（风险比=0.01，95%CI 0.00-0.34，P=0.010）。
西罗莫司是 HR 阳性晚期乳腺癌患者的一种潜在有效治疗选择。
