Diagnostic value of applying preoperative breast ultrasound and clinicopathologic features to predict axillary lymph node burden in early invasive breast cancer: a study of 1247 patients.

BACKGROUND: Since the Z0011 trial, the assessment of axillary lymph node status has been redirected from the previous assessment of the occurrence of lymph node metastasis alone to the assessment of the degree of lymph node loading. Our aim was to apply preoperative breast ultrasound and clinicopathological features to predict the diagnostic value of axillary lymph node load in early invasive breast cancer. METHODS: The 1247 lesions were divided into a high lymph node burden group and a limited lymph node burden group according to axillary lymph node status. Univariate and multifactorial analyses were used to predict the differences in clinicopathological characteristics and breast ultrasound characteristics between the two groups with high and limited lymph node burden. Pathological findings were used as the gold standard. RESULTS: Univariate analysis showed significant differences in ki-67, maximum diameter (MD), lesion distance from the nipple, lesion distance from the skin, MS, and some characteristic ultrasound features (P < 0.05). In multifactorial analysis, the ultrasound features of breast tumors that were associated with a high lymph node burden at the axilla included MD (odds ratio [OR], 1.043; P < 0.001), shape (OR, 2.422; P = 0.0018), hyperechoic halo (OR, 2.546; P < 0.001), shadowing in posterior features (OR, 2.155; P = 0.007), and suspicious lymph nodes on axillary ultrasound (OR, 1.418; P = 0.031). The five risk factors were used to build the predictive model, and it achieved an area under the receiver operating characteristic (ROC) curve (AUC) of 0.702. CONCLUSION: Breast ultrasound features and clinicopathological features are better predictors of high lymph node burden in early invasive breast cancer, and this prediction helps to develop more effective treatment plans.

Automated Breast Ultrasound (ABUS)-based radiomics nomogram: an individualized tool for predicting axillary lymph node tumor burden in patients with early breast cancer.

OBJECTIVES: Preoperative evaluation of axillary lymph node (ALN) status is an essential part of deciding the appropriate treatment. According to ACOSOG Z0011 trials, the new goal of the ALN status evaluation is tumor burden (low burden, < 3 positive ALNs; high burden, ≥ 3 positive ALNs), instead of metastasis or non-metastasis. We aimed to develop a radiomics nomogram integrating clinicopathologic features, ABUS imaging features and radiomics features from ABUS for predicting ALN tumor burden in early breast cancer. METHODS: A total of 310 patients with breast cancer were enrolled. Radiomics score was generated from the ABUS images. Multivariate logistic regression analysis was used to develop the predicting model, we incorporated the radiomics score, ABUS imaging features and clinicopathologic features, and this was presented with a radiomics nomogram. Besides, we separately constructed an ABUS model to analyze the performance of ABUS imaging features in predicting ALN tumor burden. The performance of the models was assessed through discrimination, calibration curve, and decision curve. RESULTS: The radiomics score, which consisted of 13 selected features, showed moderate discriminative ability (AUC 0.794 and 0.789 in the training and test sets). The ABUS model, comprising diameter, hyperechoic halo, and retraction phenomenon, showed moderate predictive ability (AUC 0.772 and 0.736 in the training and test sets). The ABUS radiomics nomogram, integrating radiomics score with retraction phenomenon and US-reported ALN status, showed an accurate agreement between ALN tumor burden and pathological verification (AUC 0.876 and 0.851 in the training and test sets). The decision curves showed that ABUS radiomics nomogram was clinically useful and more excellent than US-reported ALN status by experienced radiologists. CONCLUSIONS: The ABUS radiomics nomogram, with non-invasive, individualized and precise assessment, may assist clinicians to determine the optimal treatment strategy and avoid overtreatment.

Value of shear wave elasticity in predicting the efficacy of neoadjuvant chemotherapy in different molecular types.

PURPOSE: The purpose of this study was to evaluate the response to neoadjuvant chemotherapy (NAC) of different molecular subtypes of breast cancer using shear wave ultrasound elastography (SWE). METHODS: Ninety-eight patients with final diagnoses of breast cancer prior to NAC were examined with SWE and B-mode ultrasound. These parameters were compared with the response evaluation criteria in solid tumors (RECIST) index and pathological diagnoses. Then, we recorded the area under the receiver operating characteristic (ROC) curve. Immunohistochemical markers, including estrogen receptor (ER), progesterone receptor (PR), Ki67 index, and human epidermal growth factor receptor 2 (HER2) score, were examined before neoadjuvant treatment. Then, the diagnostic efficacy of SWE in different molecular subtypes was evaluated. RESULTS: One-way analysis of variance revealed that age, tumor margin, the change in tumor size after chemotherapy, and the average (Emean), minimum (Emin), and maximum (Emax) values from shear wave elastography ultrasound before chemotherapy were related to the RECIST index. Multivariate regression revealed that age, tumor margin, the change in tumor size after chemotherapy, and Emax were independently correlated with the RECIST index. According to the ROC curve, the area under the curve (AUC) of Emax was 0.773. The AUC of Emean, Emin, and the ratio between tumor tissue and normal tissue (EI) were 0.630, 0.617, and 0.510, respectively. The Emax, Emin, Emean, and EI before and after NAC were significantly different (p ≤ 0.05). There was statistical significance in Luminal B type and HER2 enriched type in correlation results of the Emax values and RECIST indexes of different molecular subtypes. However, there was no significant difference in the Luminal A type and Triple negative types. There was no significant difference in the Emax values before NAC between the pathologic complete response (pCR) group and the non-pCR group (p > 0.05). CONCLUSION: Emax can be used to predict the response to NAC in women with invasive breast cancer, especially those with the Luminal B type and HER2 enriched type, but it cannot be used to predict pCR to NAC.

The value of preoperative sentinel lymph node contrast-enhanced ultrasound for breast cancer: a large, multicenter trial.

OBJECTIVE: The study conducted a multicenter study in China to explore the learning curve of contrast enhanced ultrasound (CEUS) for sentinel lymph nodes (SLNs), the feasibility of using this technique for the localization of SLNs and lymphatic channels (LCs) and its diagnostic performance for lymph node metastasis. METHOD: Nine hundred two patients with early invasive breast cancer from six tertiary class hospitals in China were enrolled between December 2016 and December 2019. Each patient received general ultrasound scanning and SLN-CEUS before surgery. The locations and sizes of LCs and SLNs were marked on the body surface based on observations from SLN-CEUS. These body surface markers were then compared with intraoperative blue staining in terms of their locations. The first 40 patients from each center were included in determining the learning curve of SLN-CEUS across sites. The remaining patients were used to investigate the diagnostic efficacy of this technique in comparison with intraoperative blue staining and pathology respectively. RESULT: The ultrasound doctor can master SLN-CEUS after 25 cases, and the mean operating time is 22.5 min. The sensitivity, specificity, negative predictive value, and positive predictive value of SLN-CEUS in diagnosing lymph node metastases were 86.47, 89.81, 74.90, and 94.97% respectively. CONCLUSION: Ultrasound doctors can master SLN-CEUS with a suitable learning curve. SLN-CEUS is a feasible and useful approach to locate SLNs and LCs before surgery and it is helpful for diagnosing LN metastases.

Highly penetrating nanobubble polymer enhances LINC00511-siRNA delivery for improving the chemosensitivity of triple-negative breast cancer.

Ultrasound-mediated nanobubble destruction (UMND), which can utilize the physical energy of ultrasound irradiation to improve the transfer efficiency to target cells is becoming one of the most promising carriers for gene delivery. The purpose of this study was to establish cell-penetrating peptide (CPP)-loaded nanobubbles (CNBs) connected with long intergenic nonprotein coding RNA 00511-small interfering RNA (LINC00511-siRNA) and evaluate its feasibility for improving the chemosensitivity of triple-negative breast cancer in vitro. First, fluorescence imaging confirmed the loading of siLINC00511 on CNBs, and the CNBs-siLINC00511 were characterized by the Zetasizer Nano ZS90 analyzer and transmission electron microscopy. Next, cell counting kit 8 assay was used to detect the inhibitory activity of cisplatin on the proliferation of MDA-MB-231 cells, and the 50% inhibition concentration value before and after transfer was calculated. Finally, the silencing effect of siLINC00511 was evaluated in vitro using an apoptosis assay, transwell assay, real time-PCR and western blotting. UMND combined with CNBs could effectively transfer the siRNA to MDA-MB-231 cells, thus evidently reducing the expression of LINC00511. Furthermore, inhibitory activity of cisplatin on MDA-MB-231 cells was enhanced after downregulation of LINC00511 expression. Downregulation of LINC00511 alters expression of cell cycle-related (CDK 6) and apoptosis-related (Bcl-2 and Bax) proteins in MDA-MB-231 cells. These results suggested that siRNA-CNBs may be an ideal vector for the treatment of tumors, with high efficiency RNA interference under the combined action of UMND. It may provide a new therapeutic method for triple negative breast cancer.