HER2 Low

HER2 低
  • 文章类型: Journal Article
    背景:准确测定人表皮生长因子受体2(HER2)对于选择最佳HER2靶向治疗策略很重要。HER2低目前被认为是HER2阴性,但患者可能有资格接受新的抗HER2药物偶联物.
    目的:使用乳腺MRIBI-RADS特征对三种HER2水平进行分类,首先区分HER2-零和HER2-低/正(任务-1),然后区分HER2低和HER2阳性(任务2)。
    方法:回顾性。
    方法:621浸润性导管癌,245HER2-零,191HER2低,和185个HER2阳性。对于Task-1,488个案例用于培训,133个案例用于测试。对于任务2,有294个案例用于培训,82个案例用于测试。
    3.0T;3DT1加权DCE,短时反演恢复T2和单发EPIDWI。
    结果:比较了病理信息和BI-RADS特征。随机森林用于选择MRI特征,然后是四种机器学习(ML)算法:决策树(DT),支持向量机(SVM),k-最近邻(k-NN),和人工神经网络(ANN),用于构建模型。
    方法:卡方检验,单向方差分析,并进行了Kruskal-Wallis试验。P值<0.05被认为具有统计学意义。对于ML模型,生成的概率用于构建ROC曲线.
    结果:瘤周水肿,多病灶和非肿块强化(NME)的存在存在显著差异.为了区分HER2-零与非零(低+正),多发性病变,水肿,margin,选择肿瘤大小,并且k-NN模型在训练集中达到了0.86的最高AUC,在测试集中达到了0.79。为了区分低HER2和阳性HER2,多发性病变,水肿,并选择了保证金,DT模型在训练集中达到0.79的最高AUC,在测试集中达到0.69。
    结论:放射科医师从术前MRI读取的BI-RADS特征可以使用更复杂的特征选择和ML算法进行分析,以建立HER2状态分类模型并识别HER2低。
    方法:
    阶段2.
    BACKGROUND: Accurate determination of human epidermal growth factor receptor 2 (HER2) is important for choosing optimal HER2 targeting treatment strategies. HER2-low is currently considered HER2-negative, but patients may be eligible to receive new anti-HER2 drug conjugates.
    OBJECTIVE: To use breast MRI BI-RADS features for classifying three HER2 levels, first to distinguish HER2-zero from HER2-low/positive (Task-1), and then to distinguish HER2-low from HER2-positive (Task-2).
    METHODS: Retrospective.
    METHODS: 621 invasive ductal cancer, 245 HER2-zero, 191 HER2-low, and 185 HER2-positive. For Task-1, 488 cases for training and 133 for testing. For Task-2, 294 cases for training and 82 for testing.
    UNASSIGNED: 3.0 T; 3D T1-weighted DCE, short time inversion recovery T2, and single-shot EPI DWI.
    RESULTS: Pathological information and BI-RADS features were compared. Random Forest was used to select MRI features, and then four machine learning (ML) algorithms: decision tree (DT), support vector machine (SVM), k-nearest neighbors (k-NN), and artificial neural nets (ANN), were applied to build models.
    METHODS: Chi-square test, one-way analysis of variance, and Kruskal-Wallis test were performed. The P values <0.05 were considered statistically significant. For ML models, the generated probability was used to construct the ROC curves.
    RESULTS: Peritumoral edema, the presence of multiple lesions and non-mass enhancement (NME) showed significant differences. For distinguishing HER2-zero from non-zero (low + positive), multiple lesions, edema, margin, and tumor size were selected, and the k-NN model achieved the highest AUC of 0.86 in the training set and 0.79 in the testing set. For differentiating HER2-low from HER2-positive, multiple lesions, edema, and margin were selected, and the DT model achieved the highest AUC of 0.79 in the training set and 0.69 in the testing set.
    CONCLUSIONS: BI-RADS features read by radiologists from preoperative MRI can be analyzed using more sophisticated feature selection and ML algorithms to build models for the classification of HER2 status and identify HER2-low.
    METHODS:
    UNASSIGNED: Stage 2.
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  • 文章类型: Journal Article
    目的:本研究的目的是评估低HER2的临床病理特征和预后意义。纤维化病灶(FF),和HER2阴性乳腺癌患者的肿瘤浸润淋巴细胞(TIL)。
    方法:我们回顾性回顾了293例HER2阴性患者的数据,I-II阶段,非特异性类型的浸润性乳腺癌。HER2阴性病例分为低HER2和0HER2。使用苏木精-伊红染色的整个载玻片图像的数字分析来评估FF表达。还使用全幻灯片图像评价TIL。此外,HER2低,FF,和TILs及其预后意义进行了分析。
    结果:研究队列包括178例(60.8%)低HER2患者和115例(39.2%)0HER2患者。年纪大了,较低的诺丁汉组织学等级(NHG),雌激素受体(ER)阳性,孕激素受体(PR)阳性,激素受体(HR)阳性均与HER2低相关。FF与年龄相关,中等和低NHG,血管浸润,人力资源积极性,HER2低状态,Ki67高表达,低TIL。单因素生存分析显示,FF与较短的无进展生存期(PFS)显著相关。分层分析表明,在HR阴性和HR阳性组中,HER2状态和TILs不影响PFS。与HR阳性(风险比[HR]=0.313)和HER2低(HR=0.272)组的FF患者相比,无FF患者的DFS更长。与HR阴性(HR=0.069)和HER20组(HR=0.129)的FF患者相比,无FF患者的DFS也明显更长。
    结论:结果表明HER2低状态和TILs表达不影响预后。然而,FF患者表现出明显的生物学特征和预后意义,特别是在HR阴性和HER20组中。这为HER2阴性乳腺癌的准确诊断和治疗提供了理论基础。
    OBJECTIVE: The aim of this study is to evaluate the clinicopathological features and prognostic significance of HER2 low, fibrotic focus (FF), and tumor-infiltrating lymphocytes (TILs) in patients with HER2-negative breast cancer.
    METHODS: We retrospectively reviewed the data of 293 patients with HER2-negative, stage I-II, invasive breast cancer of non-specific types. The HER2-negative cases were classified into HER2 low and HER2 0. Digital analysis of hematoxylin-eosin stained whole slide images was used to evaluate the FF expression. TILs were also evaluated using the Whole Slide Image. Furthermore, the association between HER2 low, FF, and TILs as well as their prognostic significance were analyzed.
    RESULTS: The study cohort included 178 cases (60.8%) with HER2 low and 115 cases (39.2%) with HER2 0. Older age, lower Nottingham histological grade (NHG), estrogen receptor (ER) positivity, progesterone receptor (PR) positivity, and hormone receptor (HR) positivity were all associated with HER2 low. FF was correlated with older age, intermediate and low NHG, vascular invasion, HR positivity, HER2 low status, high Ki67 expression, and low TILs. Univariate survival analysis showed that FF was significantly associated with shorter progression-free survival (PFS). Stratified analysis indicated that in the HR-negative and HR-positive groups, HER2 status and TILs did not affect PFS. DFS was longer in patients without FF compared to those with FF in the HR-positive (hazard ratio [HR] = 0.313) and HER2 low (HR = 0.272) groups. DFS was also significantly longer in patients without FF compared to those with FF in the HR-negative (HR = 0.069) and HER2 0 groups (HR = 0.129).
    CONCLUSIONS: The results indicated that the HER2 low status and the TILs expression did not impact prognosis. However, patients with FF exhibited distinct biological characteristics and prognostic significance, particularly in the HR-negative and HER2 0 groups. This provides a rationale for accurate diagnosis and treatment of HER2-negative breast cancer.
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  • 文章类型: Journal Article
    背景:对具有低HER2表达作为独特亚型的乳腺癌的兴趣正在增加。我们旨在探讨低HER2和零HER2乳腺癌在新辅助治疗后的预后和病理完全缓解(pCR)率方面的差异。
    方法:使用国家癌症数据库(NCDB)选择2004年至2017年接受新辅助治疗的乳腺癌患者。构建Logistic回归模型进行pCR分析。采用Cox比例风险回归模型和Kaplan-Meier法进行生存分析。
    结果:共纳入41500例乳腺癌患者,其中14814例(35.7%)有HER2-0肿瘤,26686例(64.3%)有低HER2.与HER2零相比,低HER2肿瘤更常见的HR阳性(66.3%对47.1%,P<0.001)。在整个队列中(OR=0.90;95%CI[0.86-0.95];P<0.001)和HR阳性子集(OR=0.87;95%CI[0.81-0.94];P<0.001)中,低HER2肿瘤的pCR率低于HER2-零肿瘤。低HER2肿瘤患者的生存率明显优于零HER2肿瘤患者(HR=0.90;95%CI[0.86-0.94];P<0.001)。无论人力资源状况如何。此外,在HER2IHC1+和HER2IHC2+/ISH阴性(HR=0.91;95%CI[0.85-0.97];P=0.003)队列之间也观察到了微小的生存差异.
    结论:低HER2肿瘤是一种与HER2零肿瘤不同的临床相关乳腺癌亚型。这些发现可能为将来针对该亚型的适当治疗策略提供线索。
    The interest in breast cancer with low HER2 expression as a distinct subtype is increasing. We aimed to explore the differences between HER2-low and HER2-zero breast cancer in their prognosis and rate of pathological complete response (pCR) after neoadjuvant therapy.
    The National Cancer Database (NCDB) was used to select patients with breast cancer who received neoadjuvant therapy from 2004 to 2017. Logistic regression model was constructed for analysis of pCR. Cox proportional hazards regression model and Kaplan-Meier method were used for survival analysis.
    A total of 41500 breast cancer patients were included, among which 14814 (35.7%) had HER2-zero tumors and 26686 (64.3%) had HER2-low. HER2-low tumors were more commonly HR-positive in comparison with HER2-zero (66.3% versus 47.1%, P < 0.001). A lower rate of pCR was observed in HER2-low tumors than in HER2-zero tumors after neoadjuvant therapy in the total cohort (OR = 0.90; 95% CI [0.86-0.95]; P < 0.001) and in the subset of HR-positive (OR = 0.87; 95% CI [0.81-0.94]; P < 0.001). Patients with HER2-low tumors had a significantly superior survival than those with HER2-zero tumors (HR = 0.90; 95% CI [0.86-0.94]; P < 0.001), regardless of the HR status. Additionally, a marginal survival difference was also observed between HER2 IHC1+ and HER2 IHC2+/ISH-negative (HR = 0.91; 95% CI [0.85-0.97]; P = 0.003) cohorts.
    HER2-low tumors are a clinically relevant breast cancer subtype that is distinct from HER2-zero tumors. These findings may provide clues to appropriate therapeutic strategies for this subtype in the future.
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  • 文章类型: Journal Article
    背景:人表皮生长因子受体(HER2)低表达的乳腺癌越来越被认为是一种独特的亚型,由HER2免疫组织化学(IHC)1+和HER2IHC2+/原位杂交(ISH)阴性的类型组成。我们的目标是评估HER2IHC1+和HER2IHC2+/ISH阴性乳腺癌患者之间的生存差异,并构建HER2低患者的预后列线图。
    方法:纳入2010年至2015年诊断为低HER2-novo转移性乳腺癌的患者,并使用国家癌症数据库(NCDB)进行分析。采用Cox比例风险回归模型和Kaplan-Meier(KM)法进行生存分析。建立列线图来预测生存。
    结果:共7897例患者纳入最终分析,其中5458例(69.1%)为HER2IHC1+,2439例(30.9%)为HER2IHC2+/ISH阴性.尽管Kaplan-Meier生存分析显示生存率存在差异,这种生存差异在多变量Cox分析中消失(多变量:HR(风险比)=0.97;95%CI(置信区间)[0.92-1.03]).成功构建了预后列线图,用于单独预测低HER2患者的长期生存率。在训练(C指数:0.719)和验证队列(C指数:0.706)中表现出可接受的预测能力。此列线图可以轻松地将患者分为具有不同预后的高风险和低风险亚组。
    结论:我们的数据表明HER21+和HER2+乳腺癌之间没有统计学差异。此外,我们构建的列线图具有可接受的能力,可以单独预测低HER2转移性乳腺癌患者的长期结局.
    Breast cancer with low human epidermal growth factor receptor (HER2) expression is increasingly considered as a distinct subtype which consists of types of HER2 immunohistochemistry (IHC) 1+ and HER2 IHC 2+/in-situ hybridization (ISH)-negative. We aim to assess the survival difference between HER2 IHC 1+ and HER2 IHC 2+/ISH-negative breast cancer patients with metastasis at presentation and construct a prognostic nomogram for HER2-low patients.
    Patients diagnosed with de novo metastatic HER2-low breast cancer from 2010 to 2015 were included and analyzed using the National Cancer Database (NCDB). Cox proportional hazards regression model and Kaplan-Meier (KM) method were used for survival analysis. Nomograms were built to predict survival.
    A total of 7897 patients were included in the final analysis, among which 5458 (69.1%) patients were HER2 IHC 1+ and 2439 (30.9%) were HER2 IHC 2+/ISH-negative. Although the Kaplan-Meier survival analysis showed difference in survival, this survival difference was lost in the multivariate Cox analysis (multivariate: HR (hazard ratio) = 0.97; 95% CI (confidence interval) [0.92-1.03]). A prognostic nomogram was successfully constructed for individually predicting the long-term survival rate of HER2-low patients, which exhibited an acceptable predictive capability in training (C index: 0.719) and validation cohort (C index: 0.706). This nomogram could easily divide patients into high and low-risk subgroups with distinct prognoses.
    Our data suggest no statistical survival differences between HER2 1+ and HER2 2+ breast cancer. Additionally, a nomogram was constructed with an acceptable capacity to individually predict the long-term outcome of HER2-low metastatic breast cancer patients.
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  • 文章类型: Journal Article
    目的:人表皮生长因子受体2(HER2)的状态对于乳腺癌的治疗决策很重要,通常通过芯针活检(CNB)来确定。CNB与手术切除活检(SEB)的一致性已得到验证,但根据新制定的HER2状态分类尚不清楚.我们的研究旨在重新评估CNB对确定乳腺癌HER2状态的诊断价值。特别是在HER2低人群中。
    方法:连续纳入2007年1月1日至2021年12月31日在华西医院就诊的乳腺癌患者,数据来自医院信息系统。通过一致率和κ统计量计算CNB和SEB之间的HER2状态的一致性。以及灵敏度,特异性,积极的,和阴性预测值(PPV和NPV)。使用Logistic模型来探索与两种测试之间不一致相关的潜在因素。
    结果:在1829名符合条件的患者中,1097(60.0%)和1358(74.2%)在CNB和SEB之间通过病理和临床分类是一致的,分别,κ值为0.46(0.43-0.49)和0.57(0.53-0.60)。通过病理分类,在IHC1和2/ISH-亚组中,CNB的敏感性(50.9%-52.7%)和PPV(50.5%-55.2%)尤其低;然而,在HER2低人群的临床分类中,其敏感性最高(77.5%),特异性最低(73.9%).高级N个阶段可能是两个测试之间不一致的稳定指标。
    结论:CNB对确定乳腺癌HER2状态的诊断价值有限,特别是在HER2低人群中。
    OBJECTIVE: The status of human epidermal growth factor receptor 2 (HER2) is important for treatment decision-making of breast cancer and was commonly determined by core needle biopsy (CNB). The concordance of CNB with surgical excision biopsy (SEB) has been verified, but remain unclear according to the newly developed classification of HER2 status. Our study aimed to re-evaluate the diagnostic value of CNB for determining HER2 status in breast cancer, especially in the HER2-low population.
    METHODS: Eligible breast cancer patients in West China Hospital between January 1, 2007 and December 31, 2021 were enrolled consecutively and data were extracted from the Hospital Information System. The agreement of HER2 status between CNB and SEB was calculated by concordance rate and κ statistics, as well as the sensitivity, specificity, positive, and negative predictive values (PPV & NPV). Logistic models were used to explore potential factors associated with the discordance between both tests.
    RESULTS: Of 1829 eligible patients, 1097 (60.0%) and 1358 (74.2%) were consistent between CNB and SEB by pathological and clinical classifications, respectively, with κ value being 0.46 (0.43-0.49) and 0.57 (0.53-0.60). The sensitivity (50.9%-52.7%) and PPV (50.5%-55.2%) of CNB were especially low among IHC 1+ and 2+/ISH - subgroups by pathological classifications; however, it showed the highest sensitivity (77.5%) and the lowest specificity (73.9%) in HER2-low population by clinical classifications. Advanced N stages might be a stable indicator for the discordance between both tests.
    CONCLUSIONS: The diagnostic value of CNB was limited for determining HER2 status in breast cancer, especially in HER2-low population.
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