PDF(Pubmed)
Abstract：
Over the last two decades, the use of Next-Generation Sequencing (NGS) in medical oncology has increased the likelihood of identifying druggable mutations that may be potentially susceptible to targeted treatments. The European Society for Medical Oncology (ESMO) currently does not recommend the use of the NGS test to determine the therapeutic course of patients with metastatic breast cancer (mBC) in daily clinical practice. However, the aim of this work is to evaluate the potential contribution of the NGS test in selecting targeted therapies for patients with mBC. Data were retrospectively collected from 101 patients diagnosed with metastatic breast cancer and treated at the Modena Cancer Center between January 2015 and April 2022. A NGS test was performed on the tumor tissue of each patient at the Laboratory of Molecular Pathology of the University Hospital of Modena. This study analyzed the clinical-pathological characteristics and mutational profile of the population using NGS tests, with a focus on actionable mutations that could be targeted in advanced stages of clinical development. The indicator of this study was to quantify the actionable mutations that resulted in a change of cancer treatment. In total, 101 patients with metastatic breast cancer were analyzed, including 86 with luminal phenotype, 10 who were HER2-positive and 5 who were triple-negative. Median age was 52 years. NGS analysis was conducted on 47 samples of primary breast cancer, 52 on metastatic sites of disease and 2 on liquid biopsies. A total of 85 gene mutations were found. The most common mutations were identified in the PIK3CA (47%), FGFR (19%) and ERBB2 genes (12%), and to a lesser extent in other genes. Of the 61 patients with pathogenic mutations, 46 (75%) had at least one actionable mutation. Of these, nine received treatment with a molecular target drug: eight patients with a mutation of the PIK3CA gene were treated with alpelisib and fulvestrant; one patient with FGFR1/2 amplifications received TAS120. Median PFS for these patients was 3.8 months. The study results show that using the NGS test on cancer tissue of metastatic breast cancer could influence the therapeutic choices, considering the small sample size and limited follow-up. About 9% of the study population had their therapy modified based on the results of NGS. The growing number of detectable mutations and increased accessibility of the test may lead to a greater number of potential therapeutic implications for the NGS assay. Perspectives suggest that NGS analysis can be implemented in daily clinical practice, particularly in contexts where a Molecular Tumor Board (MTB) is active.
摘要：
在过去的二十年里，下一代测序(NGS)在肿瘤学中的应用增加了鉴定可能对靶向治疗有潜在敏感性的药物突变的可能性.欧洲医学肿瘤学会（ESMO）目前不建议在日常临床实践中使用NGS测试来确定转移性乳腺癌（mBC）患者的治疗过程。然而,这项工作的目的是评估NGS测试在为mBC患者选择靶向治疗方面的潜在贡献.回顾性收集了2015年1月至2022年4月在摩德纳癌症中心接受治疗的101例转移性乳腺癌患者的数据。在摩德纳大学医院分子病理学实验室对每位患者的肿瘤组织进行NGS测试。这项研究使用NGS测试分析了人群的临床病理特征和突变谱，重点关注可在临床发展的晚期阶段靶向的可行突变。这项研究的指标是量化导致癌症治疗改变的可操作突变。总的来说,分析了101例转移性乳腺癌患者，包括86个管腔表型，10例HER2阳性，5例三阴性。中位年龄为52岁。对47例原发性乳腺癌样本进行了NGS分析，52在疾病的转移部位，2在液体活检上。共发现85个基因突变。最常见的突变是在PIK3CA（47％），FGFR（19％）和ERBB2基因（12％），在其他基因中也有较小的程度。61例致病突变患者中,46（75％）具有至少一个可操作的突变。其中,9例接受了分子靶向药物治疗:8例PIK3CA基因突变患者接受了alpelisib和氟维司群治疗;1例FGFR1/2扩增患者接受了TAS120治疗.这些患者的平均PFS为3.8个月。研究结果表明，对转移性乳腺癌的癌组织进行NGS测试可能会影响治疗选择，考虑到样本量小和随访有限。大约9%的研究人群根据NGS的结果修改了他们的治疗方法。可检测突变的数量增加和测试的可接近性增加可能导致NGS测定的更多潜在治疗意义。观点表明，NGS分析可以在日常临床实践中实施，特别是在分子肿瘤委员会（MTB）活跃的情况下。
