Ziyao Li

Identifying ultrasound and clinical features of breast cancer molecular subtypes by ensemble decision.

Breast cancer is molecularly heterogeneous and categorized into four molecular subtypes: Luminal-A, Luminal-B, HER2-amplified and Triple-negative. In this study, we aimed to apply an ensemble decision approach to identify the ultrasound and clinical features related to the molecular subtypes. We collected ultrasound and clinical features from 1,000 breast cancer patients and performed immunohistochemistry on these samples. We used the ensemble decision approach to select unique features and to construct decision models. The decision model for Luminal-A subtype was constructed based on the presence of an echogenic halo and post-acoustic shadowing or indifference. The decision model for Luminal-B subtype was constructed based on the absence of an echogenic halo and vascularity. The decision model for HER2-amplified subtype was constructed based on the presence of post-acoustic enhancement, calcification, vascularity and advanced age. The model for Triple-negative subtype followed two rules. One was based on irregular shape, lobulate margin contour, the absence of calcification and hypovascularity, whereas the other was based on oval shape, hypovascularity and micro-lobulate margin contour. The accuracies of the models were 83.8%, 77.4%, 87.9% and 92.7%, respectively. We identified specific features of each molecular subtype and expanded the scope of ultrasound for making diagnoses using these decision models.

Early Evaluation of Relative Changes in Tumor Stiffness by Shear Wave Elastography Predicts the Response to Neoadjuvant Chemotherapy in Patients With Breast Cancer

Neoadjuvant chemotherapy plays an important role in comprehensive therapy for breast cancer, but response prediction is imperfect. Shear wave elastography (SWE) is a novel technique that can quantitatively evaluate tissue stiffness. In this study, we sought to investigate the application value of SWE for early prediction of the response to neoadjuvant chemotherapy in patients with breast cancer.

The differences in ultrasound and clinicopathological features between basal-like and normal-like subtypes of triple negative breast cancer.

Purpose The aim of this study was to identify the ultrasound features and clinicopathological characteristics of basal-like subtype of triple negative breast cancers (TNBCs). Materials and Methods This study was approved by the ethical board of the Second Affiliated Hospital of Harbin Medical University. The patients’ clinicopathological information was available. The ultrasound features of 62 tumors from 62 TNBC patients were interpreted. The immunohistochemical results of cytokertain5/6 (CK5/6) and Epidermal Growth Factor Receptor (EGFR) were used to classify the tumor into basal-like and normal-like groups. The association of the ultrasound features interpreted by experienced ultrasound doctors with the immunohistochemical classification was studied. Results Of the 62 TNBC cases, 42 (67.7%) exhibited the basal-like phenotype and 20 (32.3%) exhibited the normal-like phenotype based on the immunohistochemical CK5/6 and EGFR markers. Of all the tumors, 90.3% were invasive carcinomas. The basal-like tumors were significantly associated with a maximum diameter on ultrasound of more than 20 mm (36, 85.7%) (P = 0.0014). The normal-like tumors usually exhibited lateral shadows (15, 75%) (P = 0.0115) as well as microlobulated margins (12, 60%) (P = 0.0204) compared to the basal-like subtype. Other ultrasound features showed no significant differences between the two groups. Conclusions Although ultrasound cannot yet be used to differentiate between the basal-like subtype and normal-like subtype of TNBC, ultrasound can be used to provide some useful information to the clinicians.

Ultrasound Utility for Predicting Biological Behavior of Invasive Ductal Breast Cancers

PURPOSE The aim of the study was to evaluate the correlation of ultrasound features with breast cancer molecular status. MATERIALS AND METHODS A retrospective review was performed of ultrasound findings in 263 patients diagnosed with breast invasive ductal carcinoma for comparison with immunohistochemistric results were obtained from each lesion. Relationships between ultrasound findings and molecular status were investigated by using multiple regression analysis by means of stepwise logistic regression. Differences in ultrasound criteria were assessed among women with different molecular status. RESULTS ER positivity was associated with small size, lobulate, angular or spiculated margin contours, absence of calcification, posterior tumor shadowing and low elasticity score; PR positivity was associated with small size, lobulate or angular or spiculated margin contours and absence of calcification; HER2 positivity was associated with presence of calcification and absence of any echogenic halo. The calculated models of predicted molecular status were accurate and discriminating with AUCs of 0.78, 0.74, and 0.74, respectively. CONCLUSIONS Breast cnacer ultrasound features show some correlation with the molecular status. These models may help to expand the scope of ultrasound in predicting tumor biology.

Identification of Personalized Chemoresistance Genes in Subtypes of Basal-Like Breast Cancer Based on Functional Differences Using Pathway Analysis.

Breast cancer is a highly heterogeneous disease that is clinically classified into several subtypes. Among these subtypes, basal-like breast cancer largely overlaps with triple-negative breast cancer (TNBC), and these two groups are generally studied together as a single entity. Differences in the molecular makeup of breast cancers can result in different treatment strategies and prognoses for patients with different breast cancer subtypes. Compared with other subtypes, basal-like and other ER+ breast cancer subtypes exhibit marked differences in etiologic factors, clinical characteristics and therapeutic potential. Anthracycline drugs are typically used as the first-line clinical treatment for basal-like breast cancer subtypes. However, certain patients develop drug resistance following chemotherapy, which can lead to disease relapse and death. Even among patients with basal-like breast cancer, there can be significant molecular differences, and it is difficult to identify specific drug resistance proteins in any given patient using conventional variance testing methods. Therefore, we designed a new method for identifying drug resistance genes. Subgroups, personalized biomarkers, and therapy targets were identified using cluster analysis of differentially expressed genes. We found that basal-like breast cancer could be further divided into at least four distinct subgroups, including two groups at risk for drug resistance and two groups characterized by sensitivity to pharmacotherapy. Based on functional differences among these subgroups, we identified nine biomarkers related to drug resistance: SYK, LCK, GAB2, PAWR, PPARG, MDFI, ZAP70, CIITA and ACTA1. Finally, based on the deviation scores of the examined pathways, 16 pathways were shown to exhibit varying degrees of abnormality in the various subgroups, indicating that patients with different subtypes of basal-like breast cancer can be characterized by differences in the functional status of these pathways. Therefore, these nine differentially expressed genes and their associated functional pathways should provide the basis for novel personalized clinical treatments of basal-like breast cancer.

Ultrasound Features of Breast Cancer for Predicting Axillary Lymph Node Metastasis

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.

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.

Intravoxel incoherent motion magnetic resonance imaging for breast cancer: A comparison with benign lesions and evaluation of heterogeneity in different tumor regions with prognostic factors and molecular classification

The objective of the present study was to compare the differentiation between breast cancer and benign breast lesions and study regional distribution characteristics in various subtypes of breast cancer using intravoxel incoherent motion (IVIM) parameters. This retrospective study involved 119 patients with breast cancer and 22 patients with benign breast lesions, who underwent 3.0T breast magnetic resonance imaging examinations. The apparent diffusion coefficient (ADC) and IVIM parameters (slow ADC, fast ADC and fraction of fast ADC) were obtained from patients with breast cancer and benign lesions using diffusion-weighted imaging (DWI) with b-values of 0, 50, 100, 150, 200, 400, 500, 1,000 and 1,500 sec/mm2. Compared with patients with benign breast lesions, patients with breast cancer exhibited decreased ADC (P<0.001), slow ADC (P<0.001) and fast ADC (P<0.001) values, and higher fraction of fast ADC (P<0.001) values. Tumors with metastatic axillary lymph nodes demonstrated increased fraction of fast ADC values (P<0.001) and decreased slow ADC values (P<0.001) compared with tumors without metastatic axillary lymph nodes. The Fast ADC values of tumor tissues in estrogen receptor (ER) and progesterone receptor (PR) negative groups were higher than in positive groups (P<0.001), and the slow ADC values of tumor tissues were lower in ER and PR negative groups than positive groups (P<0.001). Luminal B (HER2- negative) tumor (P<0.001) and peritumor (P<0.001) tissues exhibited decreased fraction of fast ADC values, in comparison with other subtypes. Triple-negative breast cancer (TNBC) tumor tissue exhibited increased fast ADC (P<0.001) and fraction of fast ADC values (P<0.001), and decreased slow ADC values (P<0.001), when compared with other subtypes. The TNBC tumor edge tissues had increased fraction of fast ADC values compared with other subtypes (P<0.01) and TNBC tumor tissues (P<0.05). Therefore, the IVIM parameters of tumor, tumor edge and peritumor tissues in various subtypes of breast cancer may be useful for differentiation of breast cancer subtypes and to assess the invasive extent of the tumors.