Cejalvo Juan Miguel, Pérez-Fidalgo J Alejandro, Ribas Gloria, Burgués Octavio, Mongort Cristina, Alonso Elisa, Ibarrola-Villava Maider, Bermejo Begoña, Martínez María Teresa, Cervantes Andrés, Lluch Ana
Department of Haematology and Medical Oncology. Hospital Clínico Universitario, Biomedical Research Institute INCLIVA, University of Valencia, AVD/Blasco Ibánez, 17, 46010, Valencia, Spain.
Department of Pathology. Hospital Clínico Universitario, Biomedical Research Institute INCLIVA, University of Valencia, Valencia, Spain.
Breast Cancer Res Treat. 2016 Nov;160(1):69-77. doi: 10.1007/s10549-016-3980-z. Epub 2016 Sep 14.
There is increasing interest in the molecular profiling of tumour tissues in order to investigate alternative breast cancer (BC) therapies. However, the impact of genomic screening for druggable mutations with targeted gene panel sequencing (TGPS) in routine practice remains controversial.
This is a retrospective analysis of data from a genomic screening programme at our institution, in which we performed simplified TGPS for mutations in PIK3CA, AKT1, KRAS, NRAS, and BRAF in order to select patients for targeted therapy clinical trials. The genomes of archived samples of primary (PT) and/or metastatic (MT) tumours from advanced BC patients were analysed with MassARRAY technology (Sequenom MassARRAY, OncoCarta v1.0). The level of PTEN expression was assessed by immunohistochemistry. The primary endpoint was to identify the proportion of BC patients with PI3 K and MAPK alterations who were included in clinical trials using targeted therapies against these pathways.
Two hundred and fifteen metastatic BC patients (65 PT and 168 MT) were included. Fifty-two patients (24.19 %) were enrolled in tailored clinical trials, of whom 29 (55.77, 13.49 % of all patients screened) harboured mutations targeted by the study drug. Moreover, 12 wild-type patients out of the 215 (5.58 %) were included in the clinical trials for which mutation analysis was an inclusion criteria. All the patients received drugs targeting the PI3K-AKT pathway and only two were given combinations directed against the PI3K and MAPK pathways. PI3KCA mutations were present in 33.7 % (61/181) of the patients, 45.83 % in PTs and 29.32 % in MTs. AKT1 mutations were detected in 5.48 % (8/146) of patients and PTEN loss in 34.67 % (52/150). KRAS, NRAS, and BRAF mutations were present in 12.06, 5.67, and 3.18 % of patients, respectively.
Genomic screening with a simplified TGPS is feasible, and was used to identify 13.49 % of patients who were included in clinical trials using targeted therapy against the mutations they harboured; PI3KCA mutations were the most frequent aberration in our series.
为了研究替代的乳腺癌（BC）治疗方法，人们对肿瘤组织的分子谱分析越来越感兴趣。然而，在常规实践中，通过靶向基因panel测序（TGPS）进行可靶向治疗突变的基因组筛查的影响仍存在争议。
这是对我们机构基因组筛查项目数据的回顾性分析，在该项目中，我们对PIK3CA、AKT1、KRAS、NRAS和BRAF中的突变进行了简化的TGPS，以选择患者进行靶向治疗临床试验。使用MassARRAY技术（Sequenom MassARRAY，OncoCarta v1.0）分析晚期BC患者原发肿瘤（PT）和/或转移肿瘤（MT）存档样本的基因组。通过免疫组织化学评估PTEN表达水平。主要终点是确定使用针对这些途径的靶向治疗纳入临床试验中的PI3K和MAPK改变的BC患者比例。
纳入了215例转移性BC患者（65例PT和168例MT）。52例患者（24.19%）参加了定制的临床试验，其中29例（55.77%，占所有筛查患者的13.49%）携带研究药物靶向的突变。此外，215例中的12例野生型患者（5.58%）被纳入以突变分析为纳入标准的临床试验。所有患者均接受了靶向PI3K - AKT途径的药物治疗，只有2例接受了针对PI3K和MAPK途径的联合治疗。PI3KCA突变存在于33.7%（61/181）的患者中，PT中为45.83%，MT中为29.32%。AKT1突变在5.48%（8/146）的患者中被检测到，PTEN缺失在34.67%（52/150）的患者中被检测到。KRAS、NRAS和BRAF突变分别存在于12.06%、5.67%和3.18%的患者中。
使用简化的TGPS进行基因组筛查是可行的，并用于识别13.49%的患者，这些患者被纳入使用针对其携带的突变的靶向治疗的临床试验；PI3KCA突变是我们系列中最常见的异常。
