基于 DNA 超分子水凝胶的保护性 NK 细胞储库用于增强三阴性乳腺癌治疗
Protective NK Cell Reservoir Based on DNA Supramolecular Hydrogel for Enhanced Triple-Negative Breast Cancer Therapy.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
根据 PAM50 内在亚型评估 CDK4/6 抑制剂联合内分泌治疗在激素受体阳性/HER2 阴性晚期乳腺癌中的疗效结局：SOLTI-1801 CDK-PREDICT 研究的主要结果
英文原题：Efficacy outcomes of CDK4/6 inhibitors in combination with endocrine therapy treatment in hormone receptor-positive/HER2-negative advanced breast cancer according to PAM50 intrinsic subtype: Primary results of SOLTI-1801 CDK-PREDICT study.
查看英文原题
Efficacy outcomes of CDK4/6 inhibitors in combination with endocrine therapy treatment in hormone receptor-positive/HER2-negative advanced breast cancer according to PAM50 intrinsic subtype: Primary results of SOLTI-1801 CDK-PREDICT study.
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研究概要
本研究证实了 PAM50 IS 在接受 CDK4/6i 和 ET 治疗的 HR+/HER2-晚期 BC 中具有独立预后价值。非 luminal 亚型预后最差，凸显了该人群对新治疗策略的需求。
研究思路结论见上方概要
背景
PAM50内在亚型（IS）、细胞周期和免疫相关基因表达在HR+/HER2-晚期乳腺癌（BC）一线转移 setting 中接受CDK4/6抑制剂（CDK4/6i）和内分泌治疗（ET）的预后价值尚不清楚。本研究评估了诊断为HR+/HER2-晚期BC患者转移活检中的这些生物标志物。
方法
CDK-PREDICT 研究是一项在西班牙六家医院开展的多中心、双向性观察性队列研究。研究纳入诊断为 HR+/HER2- 晚期 BC 并在一线接受 CDK4/6i 和 ET 治疗的患者。在治疗前获取基线活检，以确定基于研究的 PAM50 IS、细胞周期和免疫相关基因表达。主要目的是使用单变量和多变量 Cox 回归模型评估 PAM50 IS 之间的无进展生存期（PFS）差异。次要目的包括总生存期（OS）、总缓解率（ORR），以及将细胞周期和免疫反应基因表达与 PFS 进行相关性分析。
结果
共纳入185例患者，中位随访时间为38.5个月。PAM50 luminal亚型占主导地位（82.7%）。非luminal亚型的中位PFS（10.2 vs. 25.7个月；HR，2.50；p < 0.001）和OS（32.3 vs. 58.1个月；HR，2.54；p < 0.001）均显著短于luminal亚型。较高的细胞周期和免疫相关基因表达，如CCNE1和PDCD1，以及TIL（肿瘤浸润淋巴细胞）与较差预后相关。
展开英文摘要原文
METHODS
CDK-PREDICT study is a multicentric, ambispective observational cohort study conducted in six Spanish hospitals. It included patients diagnosed with HR+ /HER2- advanced BC treated in the first-line setting with CDK4/6i and ET. Baseline biopsies were obtained prior to treatment to determine research-based PAM50 IS, cell cycle and immune-related gene expression. The primary objective was to evaluate progression-free survival (PFS) differences among PAM50 IS using uni- and multivariable Cox regression models. Secondary objectives included overall survival (OS), overall response rate (ORR), and correlating cell cycle and immune response gene expression with PFS.
RESULTS
A total of 185 patients were included, with a median follow-up of 38.5 months. PAM50 luminal subtypes were predominant (82.7 %). Non-luminal subtypes showed significantly shorter median PFS (10.2 vs. 25.7 months; HR, 2.50; p < 0.001) and OS (32.3 vs. 58.1 months; HR, 2.54; p < 0.001) than luminal subtypes. Higher cell cycle and immune-related genes expression, such as CCNE1 and PDCD1, as well as tumor infiltrating lymphocytes were associated with poorer outcomes.
CONCLUSIONS
This study confirms the independent prognostic value of PAM50 IS in HR+ /HER2- advanced BC treated with CDK4/6i and ET. Non-luminal subtypes exhibited the worst prognosis, underscoring the need for novel therapeutic strategies in this population.
论文信息
- 作者
- Tolosa P、Pascual T、Martínez-Saez O、Hernando C、Servitja S、Fernández Abad M、Brasó-Maristany F、Sanfeliu E
- 第一作者单位
- Medical Oncology Department, Hospital 12 de Octubre, Madrid, Spain; Instituto de Investigación Sanitaria Hospital 12 de Octubre (Imas12), Madrid, Spain; SOLTI Cancer Research Group, Barcelona, Spain. Electronic address: Pablo.tolosa@salud.madrid.org.Spain
- 通讯作者单位
- Medical Oncology Department, Hospital 12 de Octubre, Madrid, Spain; Instituto de Investigación Sanitaria Hospital 12 de Octubre (Imas12), Madrid, Spain; SOLTI Cancer Research Group, Barcelona, Spain. Electronic address: eva.ciruelos@gmail.com.Spain
- 文献类型
- 多中心研究 · 观察性研究
- 期刊
- European journal of cancer (Oxford, England : 1990)2025 Feb 25
- 原文标识
- PubMed 39779447 · DOI 10.1016/j.ejca.2024.115219