Construction and validation of a nomogram prediction model for axillary lymph node metastasis of cT1 invasive breast cancer.

OBJECTIVE: Based on the ultrasonic characteristics of the breast mass and axillary lymph nodes as well as the clinicopathological information, a model was developed for predicting axillary lymph node metastasis in cT1 breast cancer, and relevant features associated with axillary lymph node metastasis were identified. METHODS: Our retrospective study included 808 patients with cT1 invasive breast cancer treated at the Second Affiliated Hospital and the Cancer Hospital Affiliated with Harbin Medical University from February 2012 to August 2021 (250 cases in the positive axillary lymph node group and 558 cases in the negative axillary lymph node group). We allocated 564 cases to the training set and 244 cases to the verification set. R software was used to compare clinicopathological data and ultrasonic features between the two groups. Based on the results of multivariate logistic regression analysis, a nomogram prediction model was developed and verified for axillary lymph node metastasis of cT1 breast cancer. RESULTS: Univariate and multivariate logistic regression analysis indicated that palpable lymph nodes (P = 0.003), tumor location (P = 0.010), marginal contour (P < 0.001), microcalcification (P = 0.010), surrounding tissue invasion (P = 0.046), ultrasonic detection of lymph nodes (P = 0.001), cortical thickness (P < 0.001) and E-cadherin (P < 0.001) are independently associated with axillary lymph node metastasis. Using these features, a nomogram was developed for axillary lymph node metastasis. The training set had an area under the curve of 0.869, while the validation set had an area under the curve of 0.820. Based on the calibration curve, the model predicted axillary lymph node metastases were in good agreement with reality (P > 0.05). Nomogram's net benefit was good based on decision curve analysis. CONCLUSION: The nomogram developed in this study has a high negative predictive value for axillary lymph node metastasis in invasive cT1 breast c ancer. Patients with no axillary lymph node metastases can be accurately screened using this nomogram, potentially allowing this group of patients to avoid invasive surgery.

Establishment and validation of an ultrasound-based nomogram with risk stratification for short disease-free survival in breast cancer.

PURPOSE: This retrospective study aimed to develop and validate an Ultrasound (US)-based nomogram to predict short disease-free survival (short-DFS, less than 120 months DFS) in breast cancer (BC). METHODS: Nomogram was established based on a training data of 311 BC patients by multivariable logistic regression, and were assessed by discrimination, calibration, and clinical usefulness. Risk stratification was performed by X-tile. An independent testing data of 200 patients with BC was used for external validation. RESULTS: Nine predictors including three US features and six clinical parameters were screened into the nomogram by Lasso (log λ = -3.594) in training data. Better performance was obtained in the training data (C-index: 0.942) and testing data (C-index: 0.914). Calibration analysis indicated optimal agreement between nomogram predictions and actual observations (p = 0.67). Decision curve analysis showed a great clinical benefit (Youden index: 0.634). Three risk levels are low-risk (<184.0), moderate-risk (184.0-345.3) and high-risk (>345.3). Our nomograms had larger area under the receiver operating characteristic (ROC) curves compared with Magee Equation and Nottingham Prognostic models (0.942 vs. 0.824, 0.790). CONCLUSION: The US-based nomogram and the practical score system facilitate individualized prediction of short-DFS to optimize clinical decisions and improve prognosis in patients with BC.

Assessing Whether Morphological Changes in Axillary Lymph Node Have Already Occurred Prior to Metastasis in Breast Cancer Patients by Ultrasound.

Background and Objectives: Whether the morphological changes in axillary lymph node (ALN) have occurred prior to metastasis remains unclear in breast cancer (BC) patients. The aim of this study is to investigate the influence of BC for the morphology of non-metastasis ALN (N−) and, further, to improve the performance of ultrasound (US) examination for metastasis ALN (N+). Materials and Methods: In this retrospective study, 653 patients with breast mass were enrolled and divided into normal group of 202 patients with benign breast tumor, N− group of 233 BC patients with negative ALN and N+ group of 218 BC patients with positive ALN. US features of ALN were evaluated and analyzed according to long (L) and short (S) diameter, the (L/S) axis ratio, cortical thickness, lymph node edge, replaced hilum and color Doppler flow imaging (CDFI). Results: ALN US features of short diameter, replaced hilum, cortical thickness and CDFI have significant statistical differences in N− group comparing with normal group and N+ group, respectively (p < 0.05). Conclusions: Therefore, BC can affect ALN and lead to US morphological changes whether lymph node metastasis is present, which reduces the sensitivity of axillary US. The combination of US and other examination methods should be applied to improve the diagnostic performance of N+.

Predictive Value of Ultrasound Characteristics for Disease-Free Survival in Breast Cancer.

The main objective of this study was to determine the predictive value of US characteristics for disease-free survival (DFS) in BC patients. We retrospectively analyzed the ultrasonic images and clinical data of BC patients who had previously undergone breast surgery at least 10 years before study enrollment and divided them into a case group and a control group according to the cutoff value of 120 months for DFS. Correlation analysis was performed to identify US characteristics as independent predictors for DFS by multivariable logistic regression and Kaplan−Meier survival analysis. A total of 374 patients were collected, including 174 patients in the case group with short-DFS and 200 patients in the control group with long-DFS. Three US characteristics (size on US, mass shape, mass growth orientation) and two clinical factors (axillary lymph node (ALN), molecular subtypes) were identified as independent predictors for DFS (p < 0.05). The ROC curve showed good performance of the multivariate linear regression model with the area under the curve being 0.777. The US characteristics of large size, irregular shape, and nonparallel orientation were significantly associated with short-DFS, which is a promising supplementary for clinicians to optimize clinical decisions and improve prognosis in BC patients.

Association between VEGF single nucleotide polymorphism and breast cancer in the Northern China Han population.

PURPOSE: To investigate the associations of four commonly studied single nucleotide polymorphisms (SNP) of the vascular endothelial growth factor (VEGF), including -460T/C (rs833061), - 634G/C (rs2010963), - 2578C/A (rs699947), and +936T/C (rs3025039), with the incidence, aggressiveness, and tumor markers expression of breast cancer in the Northern China Han population. METHODS: Followed the genomic DNA extraction, a total of 259 patients with breast cancer (case group) and 273 healthy women (control group) underwent genotyping by PCR-LDR SNP assays. The associations between VEGF gene polymorphisms and the incidence, aggressiveness, and tumor markers expression of breast cancer were analyzed. RESULTS: Significant differences were observed in allele frequency and genotype distribution of - 634G/C between breast cancer cases and healthy controls (p = 0.006, 0.013). Individuals who carry the G allele more likely had a lower risk of breast cancer (OR, 0.866, 95% CI 0.782-0.959). Compared with CC genotype carriers, women who had the CG and GG genotypes demonstrated a relatively lower risk (OR, 0.860, 95% CI 0.757-0.978, p = 0.022; OR, 0.778, 95% CI, 0.656-0.924, p = 0.004, respectively). When we stratified the group of patients according to the status of tumor markers, a significant association of - 634G/C SNP and Ki-67 expression was observed. The CC genotype carriers were more likely to be characterized by high expression of Ki-67 (p = 0.031). Further analysis showed that the - 460T/-634C/-2578C/+936C haplotype was more associated with a higher risk of breast cancer (OR, 1.445, 95% CI 1.123-1.859, p = 0.004), whereas the - 460T/- 634G/- 2578C/+936C one was associated with a lower risk (OR, 0.736, 95% CI 0.563-0.963, p = 0.025). CONCLUSIONS: In the present study, we concluded that VEGF gene - 634G/C polymorphism is related to the incidence of breast cancer in the Han population in Northern China and also might be associated with tumor proliferation index Ki-67.

Application of Contrast-Enhanced Ultrasound in the Differential Diagnosis of Different Molecular Subtypes of Breast Cancer.

To explore the value of contrast-enhanced ultrasound (CEUS) in the differential diagnosis of molecular subtypes of breast cancer. Sixty-two cases of breast cancer were divided into luminal epithelium A or B subtype (luminal A/B), Her-2 over-expression subtype and triple negative subtype (TN). CEUS and routine ultrasonography were performed for all patients before surgery. (1) The luminal epithelium subtype contrast enhancement pattern was more likely to present with radial edge (76.92%, p < 0.05) and low perfusion (69.23%, p < 0.05). The maximum intensity (IMAX) was lower in the luminal epithelium subtype (p < 0.05). (2) The Her-2 over-expression subtype contrast enhancement pattern was more likely to present with centripetal enhancement (93.75%, p < 0.05) and perfusion defect (75.0%, p < 0.05), and the time to peak (TTP) was shorter (80.0%, p < 0.05). (3) The contrast enhancement pattern of the triple negative subtype was shown to have a clear boundary. Compared to the other two subtypes, the triple negative subtype did not have significantly different perfusion parameters (p > 0.05). (4) Our study showed that the areas under the ROC curve for radial edge, low perfusion and IMAX for the luminal epithelium subtype breast lesions were 76.5%, 75.6%, and 82.1%, respectively. Additionally, the areas under the ROC curve for centripetal enhancement, perfusion defect and TTP for the Her-2 over-expression subtype breast lesions were 68.6%, 92.4%, and 97.8%, respectively. The sensitivity, specificity, and diagnostic accuracy of clear boundaries in detecting triple negative subtype breast lesions were 90.5%, 80.0%, and 91.9%, respectively.

Heterogeneity of Triple-Negative Breast Cancer: Differences in Clinicopathologic and Ultrasound Features Between Premenopausal and Postmenopausal Patients.

OBJECTIVES: The aim of this study was to determine whether any salient differences exist in triple-negative breast cancer (TNBC) between premenopausal and postmenopausal patients by comprehensively comparing the ultrasound (US) and clinicopathologic features of these patients. METHODS: A detailed evaluation of the US and clinicopathologic features of 60 tumors from 60 patients with a diagnosis of TNBC (36 premenopausal and 24 postmenopausal women) was conducted in this retrospective study. RESULTS: Triple-negative breast cancer in premenopausal patients was more likely to show a round or oval shape and microlobulated margins, more commonly exerted effects on surrounding tissue, and showed grade 3 blood flow according to the method of Adler et al (Ultrasound Med Biol 1990; 16:553-559) compared with tumors in postmenopausal women. Triple-negative breast cancer in postmenopausal patients showed some similar US features as those observed in estrogen receptor-positive tumors, including irregular shapes, angular or spiculated margins, and nonparallel growth to the skin (P < .05 for all). CONCLUSIONS: Although US cannot be used to unequivocally identify TNBC, it can distinguish some salient US features regarding TNBC between premenopausal and postmenopausal women. Such information can then provide some valuable predictive information on the diagnosis of TNBC for clinicians.

The Value of Elasticity Contrast Index in the Differential Diagnosis of Thyroid Solid Nodules.

OBJECTIVES: To assess the clinical value of elasticity contrast index (ECI) in differentiating malignant thyroid nodules from benign ones. METHODS: Conventional ultrasound and elastography with pulsation of the carotid artery used as the compression source were retrospectively reviewed on 175 patients (143 females and 32 males; mean ± SD age, 45.17 ± 11.45 years) with 236 solid nodules (113 malignant and 123 benign). All nodules were confirmed by fine-needle aspiration or surgery to be accurately diagnosed. Elasticity contrast index values were computed and used to quantify local stiffness contrast within a nodule as determined with elastography. Elasticity contrast index values between the malignant and benign groups were compared and then related with pathological results. Diagnostic performance of this method was evaluated with use of the receiver operating characteristic curve. RESULTS: Mean ± SD ECI values for malignant thyroid nodules were significantly greater than those for benign nodules (3.67 ± 1.20 vs 1.80 ± 0.74, P < 0.01). Area under the receiver operating characteristic curve of ECI values was 0.907 (95% confidence interval, 0.867-0.948), and the best cutoff point was 2.16, leading to a sensitivity of 90.3%, specificity of 82.9%, positive predictive value of 83.7% and negative predictive value of 91.2%. CONCLUSIONS: Elasticity contrast index values can serve as a useful parameter in the differential diagnosis of solid thyroid nodules. With the use of ECI values, objective quantitative information on the tumor stiffness can be achieved to improve diagnostic confidence.

Identification of a correlation between the sonographic appearance and molecular subtype of invasive breast cancer: A review of 311 cases.

PURPOSE: To identify the ultrasound and clinical features related to the different molecular subtypes of invasive breast cancer. METHODS: Sonographic and clinical data of 311 surgically confirmed breast cancer cases were retrospectively reviewed and compared based on various subtypes. RESULTS: Luminal A (LA) breast cancers were associated with a low histologic grade, spiculated margins, an echogenic rim and posterior acoustic attenuation. The human epidermal growth factor receptor 2-positive (HER2+) subtype was characterized by a high grade, indistinct and spiculated margins, enhanced posterior acoustics, calcifications, and vascularity. Triple negative breast cancers (TNBCs) were more likely to present with a high tumor grade, circumscribed and microlobulated margins, and the absence of an echogenic rim and calcifications; to be markedly hypoechoic; and to have posterior acoustic enhancement and hypovascularity. Luminal B (LB) cancers were more likely to be associated with an indistinct margin and relative vascularity. CONCLUSION: Our study demonstrated that the sonographic and clinical features of breast cancer were significantly correlated with the molecular subtype. The imaging findings of the different subtypes and their biological implications may provide additional auxiliary information for clinical diagnosis, systemic treatment and prognosis prediction.

Clinicopathological and Ultrasonic Features of Triple-Negative Breast Cancers: A Comparison with Hormone Receptor-Positive/Human Epidermal Growth Factor Receptor-2-Negative Breast Cancers.

The purpose of this study was to analyze the clinicopathological and ultrasound characteristics of triple-negative breast cancers (TNBCs) and compare these findings with those for hormone receptor-positive (HR-positive)/human epidermal growth factor receptor-2-negative (HER-2-negative) tumors. Seventy-five TNBCs and 135 HR-positive/HER-2-negative breast cancers were reviewed. Data from conventional ultrasound, Doppler vascularity and elastography were included in the analysis. TNBCs had a higher histologic grade and Ki-67 level. On ultrasound, TNBCs often appeared as microlobulated, markedly hypo-echoic masses with an abrupt interface boundary, posterior acoustic enhancement, absence of calcifications and more characteristics of surrounding tissue. Results from multivariate regression analysis revealed that margin, posterior acoustic features and surrounding tissue features of tumors were independent predictive factors in differentiating TNBCs from HR-positive/HER-2-negative tumors. Our results suggest that a thorough evaluation of sonographic findings might be useful in discriminating between TNBCs and HR-positive/HER-2-negative tumors, which may provide accurate evidence for clinical early diagnosis.

Assessing Risk Category of Breast Cancer by Ultrasound Imaging Characteristics.

The purpose of our study was to assess the potential clinical value of ultrasound imaging in predicting risk category in patients with breast cancer. Three hundred thirty-six patients were enrolled and divided into a high-risk group (99, 29.5%) and mid- to low-risk group (237, 70.5%) according to the St. Gallen risk criteria. All data were retrospectively collected to analyze correlations between ultrasound features and risk category. The results revealed that the ultrasound features of irregular shape (p= 0.002), vertical growth orientation (p= 0.002), angular contour (p= 0.022) and high color Doppler flow imaging grade (p= 0.001) tended to be present in images of the high-risk group. Therefore, tumor ultrasound features should be recognized as an ideal option for determination of risk category in patients with breast cancer.

Ultrasound Features of Breast Cancer for Predicting Axillary Lymph Node Metastasis.

OBJECTIVES: The purpose of this study was to assess the clinical value of ultrasound (US) features of breast lesions for predicting the risk of axillary lymph node metastasis in patients with breast cancer. METHODS: In this retrospective study, 425 patients with breast cancer were recruited, and their preoperative US features and postoperative pathologic results were collected. The association of these US features of breast cancer with axillary lymph node metastasis was determined by univariate and multivariate analyses. RESULTS: Among the 425 patients, 200 (47.1%) had axillary lymph node metastasis, and 225 (52.9%) did not. The parameters of tumor shape, color Doppler flow imaging grades, histologic grade, and E-cadherin level were significantly and independently associated with axillary lymph node metastasis (P < .05 for all). CONCLUSIONS: Axillary lymph node metastasis was prone to happen in patients with US features of an irregular tumor shape and higher color Doppler flow imaging grades. Ultrasound imaging provides a promising tool for predicting axillary lymph node metastasis in patients with breast cancer.