Phase 1 Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy.
Department of Experimental Medicine, Sapienza University of Rome, 00185 Rome, Italy.
Curr Oncol. 2023 Feb 18;30(2):2501-2509. doi: 10.3390/curroncol30020191.
(1) Background: Precision oncology is opening new treatment opportunities for patients suffering from solid tumors. In the last two decades, the advent of CDK4/6 inhibitors, immunotherapy, and antibody-drug conjugates (ADC) improved survival outcomes for advanced or metastatic breast cancers (BC). Nevertheless, some patients progress to approved therapies and still maintain good clinical conditions. (2) Methods: With the aim to estimate the accrual rate to experimental precision oncology treatments, we collected molecular and clinical characteristics of BC patients evaluated at Phase 1 Unit of Fondazione Policlinico Gemelli. Clinical data were retrieved from hospital records. Molecular analysis was performed using Next-Generation Sequencing (NGS) FoundationOne CDx on tissue or blood. (3) Results: Among the 38 BC patients referred to our unit, 35 completed the genomic analysis. All patients were female with advanced (mean number of metastatic sites: 3, range 1-6) BC. Median age at our evaluation was 52 (IQR, 48-59). ECOG PS was good in 97% of the study population, although heavily pre-treated (median number of systemic treatments: 5, IQR 3-7). Half of referred patients were HR/HER2 BC, with 39% triple negative breast cancer (TNBC). NGS testing was performed on relapsed disease among most (71%) participants, in particular lymph nodes and soft tissue. Liquid biopsy was requested in 23% of cases. The median time from sample collection to NGS testing was 1 month and from diagnosis 54 months. The median value of mutations, VUS, and TMB were 6, 11, and 5, respectively. , , , , and were the genes with the highest number of molecular alterations. In 5 patients (14%), the molecular analysis was helpful to assign targeted therapy in the context of clinical trials with a median progression-free survival of 5 months. (4) Conclusions: HR/HER2 and TNBC were the most frequent subtypes referred for NGS testing. Tissue biopsy of relapsed disease was feasible in 71% of cases. The molecular analysis offered a new treatment opportunity in 14% of patients. The real benefit of these treatments remains to be evaluated in larger cohorts.
（1）背景：精准肿瘤学为实体瘤患者带来了新的治疗机会。在过去的二十年中，CDK4/6 抑制剂、免疫疗法和抗体药物偶联物（ADC）的出现改善了晚期或转移性乳腺癌（BC）患者的生存结局。然而，一些患者对已批准的治疗方法产生进展，仍保持良好的临床状况。（2）方法：为了估计实验性精准肿瘤学治疗的入组率，我们收集了在 Fondazione Policlinico Gemelli 一期单位评估的 BC 患者的分子和临床特征。临床数据从病历中检索。分子分析使用下一代测序（NGS）FoundationOne CDx 在组织或血液上进行。（3）结果：在转诊到我们单位的 38 名 BC 患者中，有 35 名完成了基因组分析。所有患者均为女性，患有晚期（转移性部位平均数量：3，范围 1-6）BC。中位年龄为 52 岁（IQR，48-59）。研究人群中 97%的 ECOG PS 良好，尽管接受了大量预处理（中位数系统性治疗数量：5，IQR 3-7）。一半的转诊患者为 HR/HER2 BC，其中 39%为三阴性乳腺癌（TNBC）。大多数（71%）参与者的复发疾病进行了 NGS 检测，特别是淋巴结和软组织。在 23%的病例中要求进行液体活检。从样本采集到 NGS 检测的中位时间为 1 个月，从诊断到 NGS 检测的中位时间为 54 个月。突变、VUS 和 TMB 的中位数分别为 6、11 和 5。、、、和 是分子改变数量最多的基因。在 5 名患者（14%）中，分子分析有助于在临床试验中分配靶向治疗，中位无进展生存期为 5 个月。（4）结论：HR/HER2 和 TNBC 是最常进行 NGS 检测的亚型。在 71%的病例中可行复发疾病的组织活检。分子分析为 14%的患者提供了新的治疗机会。这些治疗的实际获益仍有待更大队列的评估。
