CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Immune Checkpoint Inhibitors in Triple Negative Breast Cancer: The Search for the Optimal Biomarker.
Immune Checkpoint Inhibitors in Triple Negative Breast Cancer: The Search for the Optimal Biomarker.
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三阴性乳腺癌(TNBC)是一种高风险且侵袭性强的恶性肿瘤,其特征为恶性细胞表面缺乏雌激素受体(ER)和孕激素受体(PR),且人表皮生长因子2(HER2)未过表达。与其他乳腺癌亚型相比,其治疗选择有限。目前越来越多的证据表明免疫治疗在TNBC中的作用,然而临床试验的许多数据相互矛盾,因此临床医生难以将这些数据整合到临床实践中。在早期新辅助治疗背景下使用免疫治疗的标志性III期试验得出结论,与化疗加安慰剂相比,化疗联合免疫治疗提高了病理完全缓解(pCR)率,而其他研究则未发现pCR有显著改善。III期试验研究了免疫治疗在既往未经治疗的转移性TNBC中的效用,这些研究同样得出了不一致的结论。一些研究显示无获益,而另一些研究则表明在PD-L1阳性人群中总生存期有临床显著改善。目前尚不清楚哪些生物标志物最有用,且这些生物标志物的检测方法尚未标准化。鉴于免疫治疗往往具有严重和剧烈的副作用,识别应答和耐药的预测性生物标志物以增强患者选择非常重要且必要。在本综述中,我们将讨论传统生物标志物所面临的挑战以及新兴生物标志物在患者选择中的机遇。
Triple negative breast cancer (TNBC) is a high-risk and aggressive malignancy characterized by the absence of estrogen receptors (ER) and progesterone receptors (PR) on the surface of malignant cells, and by the lack of overexpression of human epidermal growth factor 2 (HER2). It has limited therapeutic options compared to other subtypes of breast cancer. There is now a growing body of evidence on the role of immunotherapy in TNBC, however much of the data from clinical trials is conflicting and thus, challenging for clinicians to integrate the data into clinical practice. Landmark phase III trials using immunotherapy in the early-stage neoadjuvant setting concluded that the addition of immunotherapy to chemotherapy improved the pathologic complete response (pCR) rate compared to chemotherapy with placebo while others found no significant improvement in pCR.
Phase III trials have investigated the utility of immunotherapy in previously untreated metastatic TNBC, and these studies have similarly arrived at inconsistent conclusions. Some studies showed no benefit while others demonstrated a clinically significant improvement in overall survival in the PD-L1 positive population. It is not yet clear which biomarkers are most useful, and assays for these biomarkers have not been standardized.
Given the often serious and severe side effects of immunotherapy, it is important and necessary to identify predictive biomarkers of response and resistance in order to enhance patient selection. In this review, we will discuss both the challenges of traditional biomarkers and the opportunities of emerging biomarkers for patient selection.
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