Yamagata Hereditary Tumor Research Center, Yamagata University School of Medicine, 2-2-2 Iida-nishi, Yamagata 990-9585, Japan.
Department of Clinical Oncology, Yamagata Prefectural Shinjo Hospital, 720-1 Kanazawa, Shinjo 996-8585, Yamagata, Japan.
Medicina (Kaunas). 2024 Nov 19;60(11):1898. doi: 10.3390/medicina60111898.
: Phyllodes tumors are rare breast neoplasms with limited therapeutic options and poorly understood molecular characteristics. This study aimed to analyze genomic alterations and treatment outcomes in advanced phyllodes tumors using Japan's national clinical genomic testing registry (C-CAT database) to identify potential therapeutic targets and predictive markers. : We conducted a retrospective analysis of 60 phyllodes tumor cases from 80,329 patients registered in the C-CAT database between June 2019 and August 2024. Comprehensive genomic profiling was performed using multiple platforms including FoundationOne CDx, NCC OncoPanel, and other approved tests. Treatment responses were evaluated according to RECIST criteria, and pathogenic variants were assessed using established databases including ClinVar and OncoKB. : The cohort's median age was 54 years (range: 13-79), with TERT promoter variants (70%), MED12 (52%), and TP53 (50%) mutations being the most frequent alterations. Forty patients received first-line chemotherapy, predominantly anthracycline-based regimens ( = 29). Although not reaching statistical significance, cases with CDKN2A and TERT alterations showed trends toward treatment resistance (OR > 3.0). One patient with a high tumor mutational burden (37/Mb) responded to pembrolizumab. Potential germline variants were identified in two cases (3.3%), involving MSH6 and TP53 alterations. Notably, no cases with CDKN2B alterations demonstrated treatment response ( = 0.09). : Our findings suggest distinct molecular patterns in phyllodes tumors compared to other soft tissue sarcomas, with potential implications for treatment selection. The identification of specific genetic alterations associated with treatment resistance may guide therapeutic decision-making, while the presence of actionable mutations in select cases indicates potential opportunities for targeted therapy approaches.
叶状肿瘤是一种罕见的乳腺肿瘤，治疗选择有限，分子特征了解甚少。本研究旨在通过日本国家临床基因组测试注册（C-CAT 数据库）分析晚期叶状肿瘤的基因组改变和治疗结果，以确定潜在的治疗靶点和预测标志物。
我们对 2019 年 6 月至 2024 年 8 月期间 C-CAT 数据库中登记的 80329 例患者中的 60 例叶状肿瘤病例进行了回顾性分析。使用包括 FoundationOne CDx、NCC OncoPanel 和其他批准的测试在内的多个平台进行全面基因组分析。根据 RECIST 标准评估治疗反应，使用包括 ClinVar 和 OncoKB 在内的既定数据库评估致病性变异。
队列的中位年龄为 54 岁（范围：13-79），最常见的改变是 TERT 启动子变异（70%）、MED12（52%）和 TP53（50%）突变。40 例患者接受了一线化疗，主要是基于蒽环类的方案（=29）。尽管没有达到统计学意义，但 CDKN2A 和 TERT 改变的病例有治疗抵抗的趋势（OR>3.0）。一名高肿瘤突变负担（37/Mb）的患者对 pembrolizumab 有反应。在 2 例（3.3%）中发现了潜在的种系变异，涉及 MSH6 和 TP53 改变。值得注意的是，没有 CDKN2B 改变的病例显示出治疗反应（=0.09）。
我们的研究结果表明，叶状肿瘤与其他软组织肉瘤相比存在明显的分子模式，这可能对治疗选择有影响。确定与治疗抵抗相关的特定遗传改变可能指导治疗决策，而在某些情况下存在可操作的突变则表明可能有机会进行靶向治疗。
