接受依维莫司治疗的ER阳性、HER2阴性晚期乳腺癌患者的预后受分子特征的影响。

IF 3.4 2区 医学 Q1 PATHOLOGY
Hélène Salaün, Lounes Djerroudi, Laura Haik, Anne Schnitzler, Guillaume Bataillon, Gabrielle Deniziaut, Ivan Bièche, Anne Vincent-Salomon, Marc Debled, Paul Cottu
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引用次数: 0

摘要

依维莫司被广泛用于ER阳性、HER2阴性的晚期乳腺癌患者。我们研究了多中心队列中作为潜在疗效生物标志物的 PIK3CA/AKT/mTOR 通路的改变。研究纳入了2012年至2014年间在两个癌症中心接受依维莫司和内分泌治疗的晚期ER阳性、HER2阴性乳腺癌患者。靶向测序检查了PIK3CA、ESR1和AKT1基因的突变。免疫化学分析评估了PTEN、INPP4B、STK11、p4EBP1和pS6的表达。我们分析了 71 例患者(44 例原发肿瘤;27 例转移组织)。中位年龄为 63 岁 [58-69]。所有患者均为晚期重症患者。在 32 个样本中观察到 PIK3CA 通路突变(15.5%、24.0% 和 5.6% 的样本中观察到 PIK3CA 第 10 和 21 号外显子以及 AKT1 第 4 号外显子),在 5 个样本(7.0%)中观察到 ESR1 突变。大多数样本显示 PIK3CA 通路蛋白在细胞质中表达。pS6或p4EBP1组织镜检中值≥的患者无进展生存期较长(6.6个月对3.7个月,p = 0.037),PTEN组织镜检中值≤的患者无进展生存期较长(7.1个月对5.3个月,p = 0.02)。pS6≥第3四分位数的患者(27.6个月对19.3个月,p = 0.038)和PIK3CA/AKT/mTOR通路发生任何突变的患者(27.6个月对19.3个月,p = 0.011)的总生存期更长。接受依维莫司治疗的ER阳性、HER2阴性晚期乳腺癌患者的预后似乎主要取决于与PIK3CA/AKT/mTOR通路激活相关的分子特征。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

The prognosis of patients treated with everolimus for advanced ER-positive, HER2-negative breast cancer is driven by molecular features

The prognosis of patients treated with everolimus for advanced ER-positive, HER2-negative breast cancer is driven by molecular features

Everolimus is widely used in patients with advanced ER-positive, HER2-negative breast cancer. We looked at alterations in the PIK3CA/AKT/mTOR pathway in a multicenter cohort as potential biomarkers of efficacy. Patients with advanced ER-positive, HER2-negative breast cancer treated with everolimus and endocrine therapy between 2012 and 2014 in two cancer centers were included. Targeted sequencing examined mutations in PIK3CA, ESR1, and AKT1 genes. An immunochemical analysis was conducted to evaluate expression of PTEN, INPP4B, STK11, p4EBP1, and pS6. We analyzed 71 patients (44 primary tumors; 27 metastatic tissues). Median age was 63 years [58–69]. All patients had heavily pretreated advanced disease. A mutation in the PIK3CA pathway was observed in 32 samples (PIK3CA exons 10 and 21 and AKT1 exon 4 in 15.5%, 24.0%, and 5.6% of samples), and in ESR1 in 5 samples (7.0%), respectively. Most samples showed cytoplasmic expression of the PIK3CA pathway proteins. Progression-free survival was longer in patients with a pS6 or p4EBP1 histoscore ≥ median value (6.6 versus 3.7 months, p = 0.037), and in patients with a PTEN histoscore ≤ median value (7.1 versus 5.3 months, p = 0.02). Overall survival was longer in patients with pS6 ≥ 3rd quartile (27.6 versus 19.3 months, p = 0.038) and in patients with any mutation in the PIK3CA/AKT/mTOR pathway (27.6 versus 19.3 months, p = 0.011). The prognosis of patients treated with everolimus for advanced ER-positive, HER2-negative breast cancer appears primarily driven by molecular features associated with the activation of the PIK3CA/AKT/mTOR pathway.

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来源期刊
Journal of Pathology Clinical Research
Journal of Pathology Clinical Research Medicine-Pathology and Forensic Medicine
CiteScore
7.40
自引率
2.40%
发文量
47
审稿时长
20 weeks
期刊介绍: The Journal of Pathology: Clinical Research and The Journal of Pathology serve as translational bridges between basic biomedical science and clinical medicine with particular emphasis on, but not restricted to, tissue based studies. The focus of The Journal of Pathology: Clinical Research is the publication of studies that illuminate the clinical relevance of research in the broad area of the study of disease. Appropriately powered and validated studies with novel diagnostic, prognostic and predictive significance, and biomarker discover and validation, will be welcomed. Studies with a predominantly mechanistic basis will be more appropriate for the companion Journal of Pathology.
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