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.
肿瘤细胞治疗研究
英文原题:Integrating traditional biomarkers and emerging predictors to assess neoadjuvant chemotherapy efficacy in breast cancer: a multifactorial analysis of Ki-67, CDK4, EGFR, TILs and ctDNA.
Integrating traditional biomarkers and emerging predictors to assess neoadjuvant chemotherapy efficacy in breast cancer: a multifactorial analysis of Ki-67, CDK4, EGFR, TILs and ctDNA.
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TNM 分类、EGFR、Ki-67、CDK4 表达、BC 亚型和 NACT 结果对 BC 患者的 pCR 具有预测价值。
本研究旨在分析接受新辅助化疗(NACT)的乳腺癌(BC)患者中,细胞增殖相关抗原Ki-67、细胞周期蛋白依赖性激酶4(CDK4)、表皮生长因子受体(EGFR)、TIL(肿瘤浸润淋巴细胞)和循环肿瘤DNA(ctDNA)表达与治疗结局及预后的相关性。
回顾性分析2018年1月1日至2021年12月31日期间在XX医院接受术前NACT的231名乳腺癌患者的临床病理资料。采用逻辑回归模型分析影响NACT疗效的因素,采用Cox风险回归模型分析预后因素。通过治疗前活检评估TIL,并在NACT期间监测ctDNA水平。研究还进行了倾向评分匹配和亚组分析。
接受4–6个周期化疗后,治疗缓解率为77.92%(180/231),其中58.87%(136/231)达到病理完全缓解(pCR)。多因素分析显示,TNM II期、EGFR阳性、Ki-67低表达、CDK4阴性、非三阴性亚型及NACT有效均与较高pCR率相关。TIL水平较高与pCR率升高相关(高TIL组72.4%,低TIL组39.1%,p<0.001)。NACT期间,达到pCR患者的ctDNA水平较未达到pCR者显著下降(p<0.001)。倾向评分匹配后,pCR组3年无病生存率显著较高(88.9%比71.1%,p=0.003)。亚组分析显示,不同乳腺癌亚型的pCR率和预测性生物标志物各不相同。
TNM分期、EGFR、Ki-67、CDK4表达、乳腺癌亚型及NACT疗效对乳腺癌患者达到pCR具有预测价值。较低TNM分期、较低Ki-67表达和EGFR阳性与较好结局相关。NACT期间TIL水平较高及ctDNA显著下降与应答改善和预后较好相关。这些发现凸显了将传统临床病理因素与新型生物标志物结合、制定乳腺癌个体化治疗策略的潜力。
This study aimed to analyse the correlation between the expression of cell proliferation-associated antigen (Ki-67), cell cycle protein-dependent kinase 4 (CDK4), epidermal growth factor receptor (EGFR), tumour-infiltrating lymphocytes (TILs) and circulating tumour DNA (ctDNA) with the outcome and prognosis of patients with breast cancer (BC) undergoing neoadjuvant chemotherapy (NACT).
We retrospectively analysed the clinicopathological data of 231 patients with BC who underwent preoperative NACT at XX Hospital between 1 January 2018 and 31 December 2021. Logistic regression models were used to analyse factors influencing NACT efficacy. The Cox risk regression model was used to analyse prognostic factors. The TILs were assessed on pre-treatment biopsies, and ctDNA levels were monitored during NACT. Propensity score matching and subgroup analyses were performed.
After 4-6 cycles of chemotherapy, the response rate was 77.92% (180/231), with 58.87% (136/231) achieving pathological complete response (pCR). Multifactorial analysis showed that tumour, node and metastasis (TNM) stage II, EGFR positivity, low Ki-67 expression, CDK4 negativity, non-triple-negative subtypes and effective NACT results were associated with higher pCR rates. Higher TIL levels correlated with increased pCR rates (72.4% for high TILs vs 39.1% for low TILs, p < 0.001). The ctDNA levels decreased significantly in patients with pCR compared with patients without pCR during NACT (p < 0.001). After propensity score matching, the 3-year disease-free survival rate was significantly higher in the pCR group (88.9% vs 71.1%, p = 0.003). Subgroup analysis revealed varying pCR rates and predictive biomarkers across BC subtypes.
The TNM classification, EGFR, Ki-67, CDK4 expression, BC subtype and NACT results have predictive value for pCR in patients with BC. Lower TNM classification, lower Ki-67 expression and EGFR positivity are associated with better outcomes. High TIL levels and significant decreases in ctDNA during NACT correlate with improved response and prognosis. These findings highlight the potential for integrating traditional clinicopathological factors with novel biomarkers for personalised treatment strategies in BC.
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