Axillary ultrasound after neoadjuvant therapy reduces the false-negative rate of sentinel lymph node biopsy in patients with cytologically node-positive breast cancer.

OBJECTIVES: This study aimed to determine whether post-neoadjuvant therapy (NAT) axillary ultrasound (AUS) could reduce the false-negative rate (FNR) of sentinel lymph node biopsy (SLNB). We also performed subgroup analyses to identify the appropriate patient for SLNB. METHODS: A total of 220 patients with cytologically proven axillary node-positive breast cancer who underwent both SLNB and axillary lymph node dissection (ALND) after NAT were included. We calculated the FNR of SLNB. In the case of post-NAT AUS results available, AUS was classified as negative or positive. Then the FNR of post-NAT AUS combined with SLNB was evaluated. Subgroup analyses based on the number of sentinel lymph nodes removed, molecular subtypes, and the clinical N stage were also performed. RESULTS: The overall axillary lymph node pathological complete response rate was 45.5% (100/220). The FNR of SLNB alone was 15.8% (95%CI: 9.2 to 22.5%). Post-NAT AUS results were available for 181 patients. When combined negative post-NAT AUS results and SLNB, the FNR was reduced to 7.5% (95%CI: 2.4 to 12.7%). Subgroup analyses of the FNR for SLNB alone and negative post-NAT AUS combined with SLNB were shown as follows: in cases patients with less than three sentinel lymph nodes (SLNs) and at least three SLNs removed, the FNR was decreased from 24.5 to 13.2%, and 9.0 to 5.0%, respectively. The FNR was decreased from 20.8 to 10.5% in HR+/HER2+subgroup, 21.4 to 16.7% in HR-/HER2+subgroup, 15.9 to 7.0% in HR+/HER2- subgroup, and 0% in HR-/HER2- subgroup, respectively. For cN1 patients, the FNR was decreased from 18.1 to 12.1% while 17.1 to 3.6% for cN2 patients and 0% for cN3 patients. CONCLUSION: Using negative post-NAT AUS may help to decrease the FNR and improve patient selection for SLNB.

Early prediction of treatment response to neoadjuvant chemotherapy based on longitudinal ultrasound images of HER2-positive breast cancer patients by Siamese multi-task network: A multicentre, retrospective cohort study.

Background: Early prediction of treatment response to neoadjuvant chemotherapy (NACT) in patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer can facilitate timely adjustment of treatment regimens. We aimed to develop and validate a Siamese multi-task network (SMTN) for predicting pathological complete response (pCR) based on longitudinal ultrasound images at the early stage of NACT. Methods: In this multicentre, retrospective cohort study, a total of 393 patients with biopsy-proven HER2-positive breast cancer were retrospectively enrolled from three hospitals in china between December 16, 2013 and March 05, 2021, and allocated into a training cohort and two external validation cohorts. Patients receiving full cycles of NACT and with surgical pathological results available were eligible for inclusion. The key exclusion criteria were missing ultrasound images and/or clinicopathological characteristics. The proposed SMTN consists of two subnetworks that could be joined at multiple layers, which allowed for the integration of multi-scale features and extraction of dynamic information from longitudinal ultrasound images before and after the first /second cycles of NACT. We constructed the clinical model as a baseline using multivariable logistic regression analysis. Then the performance of SMTN was evaluated and compared with the clinical model. Findings: The training cohort, comprising 215 patients, were selected from Yunnan Cancer Hospital. The two independent external validation cohorts, comprising 95 and 83 patients, were selected from Guangdong Provincial People's Hospital, and Shanxi Cancer Hospital, respectively. The SMTN yielded an area under the receiver operating characteristic curve (AUC) values of 0.986 (95% CI: 0.977-0.995), 0.902 (95%CI: 0.856-0.948), and 0.957 (95%CI: 0.924-0.990) in the training cohort and two external validation cohorts, respectively, which were significantly higher than that those of the clinical model (AUC: 0.524-0.588, P all < 0.05). The AUCs values of the SMTN within the anti-HER2 therapy subgroups were 0.833-0.972 in the two external validation cohorts. Moreover, 272 of 279 (97.5%) non-pCR patients (159 of 160 (99.4%), 53 of 54 (98.1%), and 60 of 65 (92.3%) in the training and two external validation cohorts, respectively) were successfully identified by the SMTN, suggesting that they could benefit from regime adjustment at the early-stage of NACT. Interpretation: The SMTN was able to predict pCR in the early-stage of NACT for HER2-positive breast cancer patients, which could guide clinicians in adjusting treatment regimes. Funding: Key-Area Research and Development Program of Guangdong Province (No.2021B0101420006); National Natural Science Foundation of China (No.82071892, 82171920); Guangdong Provincial Key Laboratory of Artificial Intelligence in Medical Image Analysis and Application (No.2022B1212010011); the National Science Foundation for Young Scientists of China (No.82102019, 82001986); Project Funded by China Postdoctoral Science Foundation (No.2020M682643); the Outstanding Youth Science Foundation of Yunnan Basic Research Project (202101AW070001); Scientific research fund project of Department of Education of Yunnan Province(2022J0249). Science and technology Projects in Guangzhou (202201020001;202201010513); High-level Hospital Construction Project (DFJH201805, DFJHBF202105).

Amplification of RAD54B promotes progression of hepatocellular carcinoma via activating the Wnt/ß-catenin signaling.

Liver cancer was reported to be the sixth most frequently diagnosed cancer, and hepatocellular carcinoma (HCC) accounts for 75%-85% of primary liver cancer. Nevertheless, the concrete molecular mechanisms of HCC progression remain obscure, which is essential to elucidate. The expression profile of RAD54B in HCC was measured using qPCR and western blotting. Moreover, the levels of RAD54B in paraffin-embedded samples were evaluated using immunohistochemistry (IHC). The effect of RAD54B on HCC progression was testified by in vitro experiments, and in vivo orthotopic xenograft tumor experiments. The mechanisms of RAD54B promoting HCC progression were investigated through molecular and function experiments. Herein, RAD54B are dramatically upregulated in HCC tissues and cell lines both on mRNA and protein levels, and RAD54B can servers as an independent prognostic parameter of 5-year overall survival and 5-year disease-free survival for patients with HCC. Moreover, up-regulation of RAD54B dramatically increases the capacity for in vitro cell viability and motility, and in vivo intrahepatic metastasis of HCC cells. Mechanistically, RAD54B promotes the HCC progression through modulating the wnt/ß-catenin signaling. Notably, blocking the wnt/ß-catenin signaling axis can counteract the activating effects of RAD54B on motility of HCC cells. Besides, further analysis illustrates that DNA amplification is one of the mechanisms leading to mRNA overexpression of RAD54B in HCC. Our findings indicate that RAD54B might be a promising potential prognostic marker and a candidate therapeutic target to therapy HCC.