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Krüppel-like zinc-finger transcription factor 5 (KLF5) is a vital regulator of breast cancer (BC) onset and progression. The mechanism by which KLF5 regulates BC is still not clearly known. In this study, bioinformatics analysis shows that BC-affected individuals with elevated KLF5 expression levels have poor clinical outcomes. We further verify that miR-145-5p regulated KLF5 expression to promote cell apoptosis and inhibit cell proliferation in BC via dual-luciferase reporter assay, western blot analysis, qRT-PCR, CCK-8 assay and cell apoptosis assay. In addition, based on bioinformatics analysis, the binding of ENST00000422059 with miR-145-5p is confirmed by dual-luciferase reporter assay. Subsequently, FISH, western blot analysis, qRT-PCR, CCK-8 and cell apoptosis assays verified that ENST00000422059 increases KLF5 protein expression by sponging miRNA to promote cell proliferation and inhibit cell apoptosis. Finally, ENST00000422059 is found to accelerate tumor progression by regulating the miR-145-5p/KLF5 axis in vivo. In conclusion, this study suggests that ENST00000422059 upregulates KLF5 by sponging miR-145-5p to promote BC progression.

Breast cancer, as the most common malignant tumor in women worldwide, has become the focus of global attention. Axillary lymph node tumor burden is an important prognostic indicator of it. Ultrasound is the most commonly used imaging method, but its sensitivity is not high, especially for the diagnosis of small and micro lymph node metastasis. In recent years, the emerging Radiomics in machine learning field has been widely used in the field of medical imaging. Because it can extract high-level information of images that is difficult to be recognized by human eyes, it has been used to establish clinical prediction models. This paper introduced the value of preoperative sonography, sketched Radiomics, and summarized the research progress of this method in predicting lymph node metastasis of breast cancer. This new method is expected to provide a reliable basis for individualized and accurate diagnosis and treatment of breast cancer.

Objectives: To develop and validate a nomogram for predicting ≥ 3 metastatic axillary lymph nodes (ALNs) in early breast cancer with no palpable axillary adenopathy by clinicopathologic data, contrast-enhanced (CE) lymphatic ultrasound (US), and grayscale findings of sentinel lymph nodes (SLNs). Materials and methods: Women with T1-2N0 invasive breast cancer were consecutively recruited for the CE lymphatic US. Patients from Center 1 were grouped into development and internal validation cohorts at a ratio of 2:1. The external validation cohort was constructed from Center 2. The clinicopathologic data and US findings of SLNs were analyzed. A nomogram was developed to predict women with ≥ 3 metastatic ALNs. Nomogram performance was assessed with the area under the receiver operating characteristic curve (AUC) and calibration curve analysis. Results: One hundred seventy-nine from Center 1 were considered the development cohorts. The remaining 90 participants from Center 1 were internal cohorts and 197 participants from Center 2 were external validation cohorts. The US findings of no enhancement (odds ratio (OR), 15.3; p = 0.01), diffuse (OR, 19.1; p = 0.01) or focal eccentric (OR, 27.7; p = 0.003) cortical thickening, and absent hilum (OR, 169.7; p < 0.001) were independently associated with ≥ 3 metastatic ALNs. Compared to grayscale US or CE lymphatic US alone, the nomogram showed the highest AUC of 0.88 (0.85, 0.91). The nomogram showed a calibration slope of 1.0 (p = 0.80–0.81; Brier = 0.066–0.067) in validation cohorts in predicting ≥ 3 metastatic ALNs. Conclusion: Patients likely to have ≥ 3 metastatic ALNs were identified by combining the lymphatic and grayscale US findings of SLNs. Our nomogram could aid in multidisciplinary treatment decision-making. Trial registration: This trial is registered on www.chictr.org.cn: ChiCTR2000031231. Registered March 25, 2020. Critical relevance statement: A nomogram combining lymphatic CEUS and grayscale US findings of SLNs could identify early breast cancer patients with low or high axillary tumor burden preoperatively, which is more applicable to the Z0011 era. Our nomogram could be useful in aiding multidisciplinary treatment decision-making for patients with early breast cancer. Key points: • CEUS can help identify and diagnose SLN in early breast cancer preoperatively. • Combining lymphatic and grayscale US findings can predict axillary tumor burden. • The nomogram showed a high diagnostic value in validation cohorts. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the preoperative diagnostic value of contrast-enhanced lymphatic ultrasound (CEUS) for the sentinel lymph node (SLN) status in early breast cancer. Materials and methods: We prospectively recruited 102 consecutive patients with clinically node-negative early breast cancer from July 2021 to October 2021. All patients underwent conventional US and percutaneous CEUS examinations. The CEUS of SLNs were classified into four enhancement patterns: homogeneous (I), featured inhomogeneous (II), focal defect (III), and no enhancement (IV). The diagnostic performance of conventional US and CEUS for SLN metastasis was assessed by receiver operating characteristic (ROC) curves and decision curves. Results: A total of 78 women were enrolled in this study, including 55, 18, and 5 patients with negative axilla, 1–2, and ≥ 3 metastastic SLNs pathologically, respectively. The identification rate of SLNs by CEUS was 100%. Patterns I and II can select 91.7% (44/48) of patients with disease-free axilla, while patterns III and IV had higher percentages of metastasis (65.2%, p < 0.001 and 57.1%, p < 0.002, respectively). For the SLN metastatic burden, 100% (48/48) of patients with pattern I/II had ≤ 2 metastatic SLNs. Compared with conventional US, the CEUS enhancement patterns showed significant improvement in diagnosing metastatic SLNs (0.813 vs 0.601, p < 0.001). CEUS had greater clinical benefits and correctly reclassified 48% of metastatic SLNs (p < 0.001) without sacrificing the classification accuracy of negative SLNs (p = 0.25), and could improve prediction accuracy by 0.42 (p < 0.001). Conclusions: CEUS demonstrated better diagnostic performance and greater clinical benefits than conventional US for the preoperative diagnosis of SLNs, showing its potential to select candidates for precluding axillary surgery in early breast cancer. Key Points: • The homogeneous and featured inhomogeneous enhancement of SLNs are highly suggestive of negative LNs, while focal defect (p < 0.001) and no enhancement (p < 0.002) patterns had higher percentages of metastasis. • The proportion of SLNs with highly suspicious signs on conventional US increases as the type of enhancement pattern increases (no suspicious signs in pattern I/II, 34.8% in pattern III, and 85.7% in pattern IV). • Compared with conventional US, CEUS improved the area under the receiver operating characteristic curve (0.813 vs. 0.601, p < 0.001) and had greater clinical benefits (IDI = 0.42, p < 0.001) for the diagnosis of axillary metastasis. [ABSTRACT FROM AUTHOR]

Objectives: Interpretation discrepancy is a major disadvantage of breast imaging. This study aimed to determine the clinical benefit of the pre-biopsy second-look breast ultrasound (US). Methods: Patients with suspicious breast masses referred to our tertiary hospital for US-guided breast biopsy were retrospectively reviewed between August 2017 and November 2019. Here, second-look assessments were performed by experienced specialized breast radiologists via performing a bilateral breast US scan plus reviewing former imaging studies, and results were compared with the initial assessment. Interpretation changes in terms of biopsy recommendation and surgical management (i.e., lumpectomy to mastectomy) were analyzed. Results: A total of 537 patients were enrolled in this study. Interpretation discrepancies occurred in 109 patients (20%; 95% CI, 17%–24%). Among them, there were 84 patients (16%; 95% CI, 13%–19%) whose masses were re-classified as BI-RADS 3 by the second-look US and underwent 2-year follow-up, showing 82 benign, 1 malignant, and 1 high-risk lesions. On the other hand, 16 patients (3%; 95% CI, 2%–5%) undertook biopsy at an additional site, identifying 10 new malignant lesions, 3 high-risk lesions, and 3 benign lesions, resulting in surgical management changes in 12 patients. In addition, nine (2%; 95% CI, 1%–3%) patients received discrepant disease ranges, which also altered surgical management. Overall, 21 patients (4%; 95% CI, 3%–6%) got their surgical management altered by the second-look US. Conclusion: Pre-biopsy second-look assessment of breast US can reduce unnecessary biopsies in 16% of patients and alter surgical management in 4% of patients, suggesting it is a practical and valuable method for patient care improvement. [ABSTRACT FROM AUTHOR]

Purpose: To validate the feasibility of S-Detect, an ultrasound computer-aided diagnosis (CAD) system using deep learning, in enhancing the diagnostic performance of breast ultrasound (US) for patients with opportunistic screening-detected breast lesions. Methods: Nine medical centers throughout China participated in this prospective study. Asymptomatic patients with US-detected breast masses were enrolled and received conventional US, S-Detect, and strain elastography subsequently. The final pathological results are referred to as the gold standard for classifying breast mass. The diagnostic performances of the three methods and the combination of S-Detect and elastography were evaluated and compared, including sensitivity, specificity, and area under the receiver operating characteristics (AUC) curve. We also compared the diagnostic performances of S-Detect among different study sites. Results: A total of 757 patients were enrolled, including 460 benign and 297 malignant cases. S-Detect exhibited significantly higher AUC and specificity than conventional US (AUC, S-Detect 0.83 [0.80–0.85] vs. US 0.74 [0.70–0.77], p < 0.0001; specificity, S-Detect 74.35% [70.10%–78.28%] vs. US 54.13% [51.42%–60.29%], p < 0.0001), with no decrease in sensitivity. In comparison to that of S-Detect alone, the AUC value significantly was enhanced after combining elastography and S-Detect (0.87 [0.84–0.90]), without compromising specificity (73.93% [68.60%–78.78%]). Significant differences in the S-Detect's performance were also observed across different study sites (AUC of S-Detect in Groups 1–4: 0.89 [0.84–0.93], 0.84 [0.77–0.89], 0.85 [0.76–0.92], 0.75 [0.69–0.80]; p [1 vs. 4] < 0.0001, p [2 vs. 4] = 0.0165, p [3 vs. 4] = 0.0157). Conclusions: Compared with the conventional US, S-Detect presented higher overall accuracy and specificity. After S-Detect and strain elastography were combined, the performance could be further enhanced. The performances of S-Detect also varied among different centers. [ABSTRACT FROM AUTHOR]

Objective: To develop a nomogram for predicting axillary lymph node (ALN) metastases using the breast imaging reporting and data system (BI-RADS) ultrasound lexicon. Methods: A total of 703 patients from July 2015 to January 2018 were included in this study as a primary cohort for model construction. Moreover, 109 patients including 51 pathologically confirmed N1 patients (TNM staging) and 58 non-metastatic patients were recruited as an external validation cohort from March 2018 to August 2019. Ultrasound images and clinical information of these patients were retrospectively reviewed. The ultrasonic features based on the BI-RADS lexicon were extracted by two radiologists. The features extracted from the primary cohort were used to develop a nomogram using multivariate analysis. Internal and external validations were performed to evaluate the predictive efficacy of the nomogram. Results: The nomogram was based on two features (size, lesion boundary) and showed an area under the curve of 0.75 (95% confidence interval [CI], 0.70–0.79) in the primary cohort and 0.91 (95% CI, 0.84–0.97) in the external validation cohort; it achieved an 88% sensitivity in N1 patients. Conclusion: The nomogram based on BI-RADS ultrasonic features can predict breast cancer ALN status with relatively high accuracy. It has potential clinical value in improving the sensitivity and accuracy of the preoperative diagnosis of ALN metastases, especially for N1 patients. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the correlation among ultrasound‐guided diffuse optical tomography (DOT), microvessel density, and breast cancer prognosis. Methods: Before surgery, the total hemoglobin (Hb) concentrations of 184 female patients with breast cancer with only a single lesion were measured. During follow‐up, 23 patients had recurrence or metastatic disease after surgery. Among these patients, 18 with recurrence or metastatic disease within 3 years after surgery were paired with 18 patients without recurrence or metastatic disease. We retrospectively reviewed the pathologic sections of those 36 patients, conducted immunohistochemical staining, and counted the microvessel densities. Then we analyzed the correlation between microvessel density and total Hb, compared total Hb and microvessel density among breast cancers with different prognoses, and tested the value of DOT in predicting the prognosis of breast cancer. Results: Microvessel density and total Hb were linearly correlated (r = 0.584; P < .001). Total Hb and microvessel density were significantly increased in the metastasis group (P = .001 and .027, respectively). A receiver operating characteristic curve analysis showed that at a total Hb cutoff value of 221.7 μmol/L, the sensitivity, specificity, and area under the curve of DOT for predicting recurrence or metastasis were 0.826, 0.516, and 0.660, respectively. Conclusions: The total Hb concentration can reflect a tumor's blood supply. Patients with a high total Hb concentration and microvessel density have a higher risk for a poorer prognosis. Total Hb can be used as an indicator of breast cancer prognosis. Diffuse optical tomography can help physicians identify patients with a high risk of metastasis and make clinical decisions. [ABSTRACT FROM AUTHOR]

Abstract: There is little evidence of an association between peripheral enhancement on contrast-enhanced ultrasound and histopathologic prognostic factors in breast cancer. The purpose of our study was to investigate the relationship of peripheral enhancement on contrast-enhanced ultrasound with microvessel density, vascular endothelial growth factor (VEGF) expression and other prognostic factors in patients with breast cancer. In 51 patients with BI-RADS (Breast Imaging Reporting and Data System) category 5 lesions scheduled for surgery, contrast-enhanced ultrasound with an 8-4 linear transducer and B-mode pulse inversion harmonic imaging was performed after administration of SonoVue. Forty-three histologically confirmed breast cancers were included in the study and divided into the peripheral enhancement group and non-peripheral enhancement group on the basis of their features on contrast-enhanced ultrasound. The ratio of peripheral to central microvessel density, VEGF expression, tumor size, histopathologic type, stage, lymph node metastasis and expression of estrogen receptor, progesterone receptor, c-erb-B2 and p53 were compared between the two groups. The ratio of peripheral to central microvessel density and a peripherally positive/centrally negative VEGF expression pattern were significantly higher in the peripheral enhancement group than in the non-peripheral enhancement group (t-test, p = 0.023, and χ2 test, p = 0.035, respectively). There were no significant differences in breast cancer size, histopathologic type, stage, lymph node metastasis or expression of estrogen receptor, progesterone receptor, c-erb-B2 and p53 between the two groups (χ2 test, p = 0.416, 0.877, 0.543, 0.124, 0.453, 0.554, 0.350 and 0.479 respectively). The peripheral enhancement pattern of breast cancer on contrast-enhanced ultrasound may be valuable in the evaluation of peripheral/central tumor angiogenesis and VEGF expression. [Copyright &y& Elsevier]

Abstract: We investigated the correlation between color Doppler flow imaging (CDFI) and ultrasound (US)-guided diffuse optical tomography (DOT) for detection of breast tumor angiogenesis. Both CDFI and DOT were performed in 214 breast lesions scheduled for biopsy. The lesions were classified as vascular or nonvascular on CDFI and total hemoglobin concentration (THC) was measured by DOT. Sonographic results were correlated with the THC measurements. Pathologic examination showed 118 breast cancers and 96 benign breast masses. When vascularization on CDFI as a sign of malignancy and a cutoff of 140 μmol/L was used, the sensitivity, specificity and accuracy were 83.9, 50.0 and 68.7% for CDFI and 83.9, 66.7 and 76.2% for DOT, respectively. Thirteen (11.0%) nonvascular breast cancers presented high THC levels. Twenty-five (52.1%) vascular benign tumors demonstrated low THC levels. Mean THC did not differ significantly in malignancies with vascular or without vascular (228.14 ± 85.37 μmol/L vs. 191.42 ± 92.59 μmol/L; p > 0.05). Likewise, for benign lesions, the difference between THC values in vascular lesions and nonvascular lesions was not statistically significant (140.86 ± 79.63 μmol/L vs. 110.13 ± 85.05 μmol/L; p > 0.05). Our results suggest that the addition of DOT to CDFI could be helpful for characterizing CDFI nonvascular lesions that are suspicious for malignancy or vascular lesions that are probably benign. [Copyright &y& Elsevier]

Abstract: Objectives: To prospectively study the ultrasound-guided near-infrared diffuse optical tomography (DOT) findings of the total haemoglobin concentration (THC) detected in invasive breast carcinomas and its contribution to the prediction of axillary lymph node (LN) status. Methods: A total of 195 invasive breast carcinomas were prospectively studied with DOT before surgery. Lumpectomy or mastectomy with full axillary nodal dissection was performed. Tumour size and THC level were correlated with LN status by a logistic regression analysis. Results: One hundred twenty-four patients (63.59%) was LN(−) and 71 (36.41%) was LN(+). The average THC was significantly higher in the LN(+) group than in the LN(−) group (252.94±69.19μmol/L versus 203.86±83.13μmol/L, P =0.01). A multivariate analysis showed an independent relationship between the probability of axillary metastasis, elevated THC level (P =0.01), and tumour size (P =0.001). The odds ratio with THC≥140μmol/L was 13.651 (1.781–104.560), whereas that of tumour size with a 1cm increment was only 1.777 (1.283–2.246). Conclusions: The THC level and the tumour size are independent and preoperative predictors of axillary nodal status; these variables may improve the diagnosis of patients with lymph node metastasis. [Copyright &y& Elsevier]