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
英文原题:Case Report: Pathologic complete response in triple negative breast cancer treated with anthracycline free regimen.
Case Report: Pathologic complete response in triple negative breast cancer treated with anthracycline free regimen.
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三阴性乳腺癌(TNBC)是一种高度侵袭性恶性肿瘤,治疗选择有限、死亡率较高。KEYNOTE-522方案的化学免疫治疗因病理完全缓解(pCR)率较高、改善生存结局,已成为新辅助治疗新标准。近期证据提示降低治疗强度具有可行性,尤其是省略蒽环类药物以减轻治疗相关毒性;但该方法尚未成为临床实践标准。本文报告一例高危TNBC患者,在省略蒽环类药物后仍达到病理完全缓解。患者为54岁白人女性,2024年2月确诊cT4a cN0 TNBC,并开始KEYNOTE-522新辅助治疗。治疗中期影像显示肿瘤显著缩小(22 mm比78 mm),支持继续第二阶段治疗。
然而表柔比星外渗后治疗必须中断,并需及时处理感染和坏死风险。排除脓毒症风险后患者接受手术,达到pCR(ypT0,ypN0)。本病例支持在特定患者中采用降阶方案的潜在价值,并提出一个待验证假设:表柔比星外渗触发的炎症反应是否增强了免疫介导的抗肿瘤效应,从而可能提高帕博利珠单抗疗效。文章还讨论缺乏经验证的患者选择预测生物标志物,以及缺乏可靠影像技术预测病理完全缓解等问题。目前TIL是唯一持续被证明可预测新辅助治疗应答的生物标志物;然而本患者TIL水平低(5%),说明该指标距离成为临床指导降阶治疗的可靠工具仍有差距。仍需进一步研究,以确定哪些患者可安全接受减量治疗而不损害结局,以及如何指导临床决策。
Triple-negative breast cancer (TNBC) is a highly aggressive malignancy with limited therapeutic options and elevated mortality rates. Chemo-immunotherapy according to the KEYNOTE-522 has established a new standard of care in the neoadjuvant setting, due to high rates of pathological complete response (pCR) and improved survival outcomes.
Recent evidence suggests the feasibility of treatment de-escalation, particularly the omission of anthracyclines, to mitigate treatment-related toxicity; however, this approach is yet to be established in clinical practice.
We report the clinical case of a complete pathological response despite the omission of anthracyclines in a patient with high-risk TNBC. A 54-year-old Caucasian woman was diagnosed in February 2024 with cT4a cN0 TNBC and started neoadjuvant treatment according to the KEYNOTE-522 regimen. Radiologic mid-treatment evaluation showed a marked reduction in tumor size (22 mm vs 78 mm), supporting continuation to the second treatment phase.
However, epirubicin extravasation required interruption of treatment, and prompt management of the risk of infection and necrosis was necessary. Once the risk of sepsis was ruled out, the patient underwent surgery, achieving pCR (ypT0, ypN0). This case supports the potential role of de-escalated regimen in selected patients and raises the hypothesis-generating question of whether the inflammatory response triggered by the extravasation of epirubicin has enhanced the immune-mediated anti-tumor effect, potentially making pembrolizumab more effective.
The lack of validate predictive biomarkers for patient selection and the absence of reliable imaging techniques to predict pathologic complete response are also discussed. Tumor-infiltrating lymphocytes (TILs) are currently the only biomarkers consistently shown to predict response to neoadjuvant treatment; however, the low TIL level observed in our patient (5%) highlights that this parameter is still far from being a reliable tool to guide treatment de-escalation in clinical practice.
Further investigation is warranted to identify which patients could safely benefit from reduced-intensity approaches without compromising outcomes and how clinicians can be guided in this decision-making process.
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