下一代肿瘤不可知靶点即将出现
Next-generation tumor-agnostic targets on the horizon.
肿瘤不可知药物开发将肿瘤学重新聚焦于共享的分子依赖性而非组织来源,从而能够针对跨肿瘤的罕见可操作驱动因素进行高效开发。
英文原题:HER2-Positive Breast Cancer: Association of MRI and Clinicopathologic Features With Tumor-Infiltrating Lymphocytes.
这项回顾性研究共纳入 212 例连续女性患者(平均年龄 54.0 岁),她们在 2017 年 1 月至 2019 年 12 月期间被诊断为 HER2 阳性乳腺癌。
背景:TIL(肿瘤浸润淋巴细胞)与人表皮生长因子受体2型(HER2)阳性乳腺癌患者的治疗结局及预后相关,临床上识别TIL水平具有重要意义。目的:探讨HER2阳性乳腺癌患者的临床病理和MRI特征与TIL水平之间的关联。方法:本回顾性研究纳入2017年1月至2019年12月连续确诊的212名女性HER2阳性乳腺癌患者,平均年龄54.0岁。患者分为TIL低水平组(<10%)和高水平组(≥10%)。3名乳腺影像科医生独立阅片,评估阅片者间一致性,后续分析采用第一位阅片者的结果。使用多变量逻辑回归分析临床病理及MRI特征与TIL水平的关系,并按激素受体(HR)状态进行亚组分析。结果:115例(54.2%)TIL水平低,97例(45.8%)水平高。TIL高水平与组织学3级(比值比[OR]=3.98;高组与低组发生率78.4%对52.2%)、肿瘤细胞密度高(OR=4.59;中位细胞密度60%对50%)、合并导管原位癌比例较低(OR=0.16;86.6%对94.8%)以及T2加权图像显示瘤周水肿比例较高(OR=2.83;71.1%对50.4%)相关,以上均P<0.05。按HR状态分层后,HR阳性/HER2阳性组中,组织学3级是高TIL水平的独立预测因素(OR=5.03,P=0.002);HR阴性/HER2阳性组中,肿瘤细胞密度高(OR=9.06,P=0.002)、瘤周水肿(OR=5.23,P=0.03)和ADC低(OR=11.69,P=0.047)为独立预测因素。3名阅片者对瘤周水肿判断的一致性为中等(κ=0.432~0.539)。结论:MRI显示瘤周水肿及提示肿瘤侵袭性的组织病理特征,有助于预测HER2阳性乳腺癌患者的高TIL水平。临床意义:治疗前MRI特征可用于评估HER2阳性乳腺癌患者的TIL水平,帮助按免疫活性及相关临床结局进行分层,并指导选择新辅助化疗、HER2靶向治疗或免疫治疗。
BACKGROUND . Tumor-infiltrating lymphocytes (TILs) are associated with therapeutic outcomes and prognosis in patients with human epidermal growth factor receptor type 2 (HER2)-positive breast cancer. Identification of TIL levels is clinically relevant. OBJECTIVE . The purpose of our study was to explore associations of clinicopathologic and MRI features with TIL levels in patients with HER2-positive breast cancer. METHODS . A total of 212 consecutive women (mean age, 54.0 years) diagnosed with HER2-positive breast cancer between January 2017 and December 2019 were included in this retrospective study. Patients were divided into low-TIL (< 10%) and high-TIL ( 10%) groups. Three breast radiologists independently reviewed images; interreader agreement was assessed, and the first reader's findings were used for further analysis. Associations of clinicopathologic and MRI features with TIL levels were evaluated using multivariable logistic regression analysis. Subanalysis of TIL levels by hormone receptor (HR) status was also performed. RESULTS . A total of 115 (54.2%) patients had low TIL levels, and 97 (45.8%) patients had high TIL levels. A high TIL level was associated (all, p < .05) with histologic grade 3 (odds ratio [OR] = 3.98; frequency, 78.4% vs 52.2% in high- vs low-TIL groups, respectively), high tumor cellularity (OR = 4.59; median cellularity, 60% vs 50%), lower frequency of associated ductal carcinoma in situ (OR = 0.16; frequency, 86.6% vs 94.8%), and higher frequency of peritumoral edema on T2-weighted images (OR = 2.83; 71.1% vs 50.4%). In subgroup analysis by HR status, histologic grade 3 (OR = 5.03, p = .002) was a significant independent predictor of high TIL level in the HR-positive/HER2-positive group, whereas high tumor cellularity (OR = 9.06, p = .002), peritumoral edema (OR = 5.23, p = .03), and low ADC (OR = 11.69, p = .047) were independent predictors of high TIL level in the HR-negative/HER2-positive group. Interreader agreement for peritumoral edema was moderate among the three radiologists ( = 0.432-0.539). CONCLUSION . Peritumoral edema on MRI and the histopathologic feature of tumor aggressiveness help predict high TIL levels in patients with HER2-positive breast cancer. CLINICAL IMPACT . Pretreatment MRI features may serve as a useful tool for assessing TIL levels in patients with HER2-positive breast cancer and for helping to classify patients with variable clinical outcomes related to immune activity and to guide selection among neoadjuvant chemotherapy or HER2-targeted therapy or immunotherapy.
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