Feasibility and reliability of sentinel lymph node biopsy after neoadjuvant chemotherapy in breast cancer patients with positive axillary nodes at initial diagnosis: An up-to-date meta-analysis of 3,578 patients.

PURPOSE: Neoadjuvant chemotherapy (NACT) is increasingly adopted in the therapy of breast cancer (BC) patients with positive axillary nodes (cN+), but the reliability and feasibility of sentinel lymph node biopsy (SLNB) following NACT are still controversial. The objective of the present study is to conduct an updated meta-analysis on this issue. METHODS: A literature search was performed using PubMed, Cochrane, Embase, and Web of Science to identify papers published from January 1, 2000 to October 22, 2020 to research SLNB after NACT in BC patients. Studies that met the quality standard were enrolled for this meta-analysis. RESULTS: A total of 3578 participants from 27 trials were included in this meta-analysis. The pooled estimate of the identification rate (IR) for SLNB was 91 %, and the false negative rate (FNR) was 15 %. The pooled negative prediction value (NPV), accuracy, specificity, and sensitivity were 82 %, 89 %, 97 %, and 85 %, respectively. In subgroup analysis, the application of dual mapping could clearly decrease the FNR. The FNR was significantly high in the luminal types, and it declined as more sentinel lymph nodes (SLNs) were removed. CONCLUSION: SLNB following NACT is now technically feasible for BC with cN+. However, it must be emphasized that the FNR is unacceptable high.

Long non-coding RNAs lnc-ANGPTL1-3:3 and lnc-GJA10-12:1 present as regulators of sentinel lymph node metastasis in breast cancer.

Long non-coding RNAs (lncRNAs) participate in various biological processed involved in tumorigenesis, metastasis and proliferation. The aim of the present study was to identify candidate long non-coding RNAs (lncRNAs) involved in sentinel lymph node (SLN) metastasis in breast cancer. Specimens of SLNs were collected from patients with SLN metastasis via punch biopsy. Total RNA was extracted and RNA sequencing (RNA-seq) was conducted. Differential expression profiles of mRNAs and lncRNAs were obtained via bioinformatics analysis, and Gene Oncology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed on differentially expressed mRNAs. The expression levels of lncRNAs were analyzed via reverse transcription-quantitative PCR (RT-qPCR), and the regulation network of the lncRNAs to downstream microRNAs (miRs) and mRNAs was predicted. Based on RNA-seq results, six differentially expressed candidate lncRNAs were identified in patients with and without SLN metastasis: lnc-ANGPTL1-3:3, lnc-GJA10-12:1, lnc-ACAN-2:1, lnc-ZPBP2-4:1, lnc-GATA3-16:1 and lnc-ACOX3-5:1. KEGG and GO analysis identified that the mitogen-activated protein kinase (MAPK) and PI3K/Akt signaling pathways were the most enriched pathways. After RT-qPCR analysis, lnc-ANGPTL1-3:3 and lnc-GJA10-12:1 exhibited expression patterns that were consistent with those from RNA-seq. Moreover, receiver operating characteristic curve analysis demonstrated that lnc-ANGPTL1-3:3 and lnc-GJA10-12:1 expression levels had high sensitivity and specificity in the diagnosis of SLN metastasis, and that their expression levels were upregulated in patients with axillary lymph node metastasis. Further analysis revealed that lnc-GJA10-12:1 and lnc-ANGPTL1-3:3 were commonly involved in regulating the miR-302 family, including miR-302d-3p and miR-302c-3p, which together targeted AKT1. Additionally, lnc-ANGPTL1-3:3 was predicted to target miR-520b to regulate MAP3K2 expression. lnc-GJA10-12:1 was also predicted to target miR-34a-5p to regulate MAP2K1 and MAP3K9 expression levels, as well as miR-449a to regulate MAP2K1 expression. The results of the present study suggested that lnc-ANGPTL1-3:3 and lnc-GJA10-12:1 may potentially serve a role in SLN metastasis of breast cancer by regulating the PI3K/Akt and MAPK signaling pathways via targeting the miR-302 family, miR-520a-3p, miR-34a-5p and miR-449a. Thus, lnc-ANGPTL1-3:3 and lnc-GJA10-12:1 in SLN may serve as potential markers of breast cancer metastasis.

Preoperative Axillary Ultrasound Helps in the Identification of a Limited Nodal Burden in Breast Cancer Patients.

Since the Z0011 trial, the clinical evaluation of axillary status has been redirected to predicting nodal tumor burden rather than nodal metastases. Our study aimed to evaluate the value of clinicopathological factors and axillary ultrasound (US) for the prediction of a high nodal burden (≥3 metastatic lymph nodes) in breast cancer patients. A total of 532 consecutive patients who underwent preoperative axillary US and subsequent surgery for clinical T1-2 breast cancer with a final pathologic analysis were included. Clinical and pathologic variables were retrospectively evaluated. Univariate and multivariate statistical analyses were performed to identify the variables that were associated with a high nodal burden. Among the 532 patients, 110 (20.7%) had a high axillary nodal burden and 422 (79.3%) had a limited nodal burden. The multivariate analysis showed that suspicious axillary US findings (P < 0.001), clinical T2 stage (P = 0.011), the presence of lymphovascular invasion (P < 0.001), and estrogen receptor positivity (P < 0.001) were significantly associated with a high nodal burden. Patients with negative axillary US findings seldom had a high nodal burden, with a negative predictive value of 93.0% (294/316). Patients with suspicious axillary US findings, clinical T2 stage, lymphovascular invasion, and estrogen receptor positivity are more likely to have a high nodal burden, which may provide additional information for the treatment plan of breast cancer patients. Preoperative axillary US helps identify a limited nodal burden in breast cancer patients and has implications for axillary lymph node dissection and adjuvant treatment.

Identification of microRNA expression in sentinel lymph nodes from patients with breast cancer via RNA sequencing for diagnostic accuracy.

BACKGROUND: Sentinel lymph node (SLN) property assessment (with or without metastasis) is important when deciding the surgery for breast cancer; however, the current diagnosis of SLN metastasis remains to be studied. microRNAs (miRNAs) have been confirmed previously as a molecular marker for the diagnosis, development and prognosis of tumors. However, the detailed role of miRNAs in the diagnosis of SLN metastasis has not been reported. METHODS: The present study aimed to explore the potential use of miRNAs in the diagnosis of SLN using RNA sequencing (RNA-seq) and a quantitative real-time polymerase chain reaction (qRT-PCR) to compare the expression profiles of miRNAs in patients with breast cancer with or without SLN metastasis. RESULTS: The RNA-seq results revealed that 1993 miRNAs were differentially expressed in patients with breast cancer with SLN metastasis. Among these miRNAs, 1960 were up-regulated and 33 were down-regulated. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses revealed that these differentially expressed miRNAs were associated with tumor growth and metastasis and were also predicted to regulate a series of tumorigenesis and metastasis genes. In particular, the most differentially expressed miRNAs were validated by qRT-PCR, such that miR-200a-3p and miR-96-5p were up-regulated and miR-1-3p and miR-486-3p were down-regulated in patients with breast cancer with SLN metastasis. CONCLUSIONS: The findings of the present study suggest that there is an association of miRNAs with SLN metastasis and also that miRNAs function as biomarkers with respect to the choice of therapy and disease prognosis.

Contrast-Enhanced Ultrasound-Guided Fine-Needle Aspiration for Sentinel Lymph Node Biopsy in Early-Stage Breast Cancer.

The purpose of this study was to assess whether translymphatic contrast-enhanced ultrasound (CEUS) combined with fine-needle aspiration (FNA) can be used pre-operatively to assess the status of axillary lymph nodes in early-stage breast cancer patients. Furthermore, we wanted to determine whether this less invasive method could potentially be a pre-operative surgical strategy. One hundred sixty-four sentinel lymph nodes (SLNs) were detected by CEUS after intradermal injection of microbubbles in 126 cases. One hundred twenty of 126 cases (95.24%) were accurately diagnosed with the SLN-FNA method. All 6 false-negative cases were due to micrometastasis or macrometastasis. There were no false-positive results after CEUS-guided FNA biopsy based on post-operative histopathological results. In conclusion, translymphatic CEUS combined with SLN-FNA is a less traumatic approach that has high accuracy in the pre-operative evaluation of axillary lymph node status. It might have the potential to be as reliable an indicator for axillary lymph node dissection as SLN biopsy.