Predicting the recurrence-free survival of phyllodes tumor of the breast: a nomogram based on clinicopathology features, treatment, and surgical margin.

Background: Grading based on histopathologic indicators cannot accurately assess the prognosis of phyllodes tumor (PT) of the breast. This article aimed to investigate the correlation between PT prognosis and clinicopathological features, treatment, and surgical margin. Methods: The clinicopathological data of patients with pathologically confirmed PT at our institution were retrospectively collected. Univariate and multivariate Cox proportional risk models were employed to test the effects of different variables on the prognosis of PT. A nomogram to predict the 1-, 3-, 5-, and 10-year recurrence-free survival (RFS) of PT was proposed, and its discriminative ability and calibration were tested using the concordance index (C-index), area under the curve (AUC), and calibration plots. All statistical analyses were performed using R. Results: A total of 342 PT patients were included, including 242 benign (70.8%), 75 borderline (21.9%) and 25 malignant (7.3%) cases. The median follow-up period was 64.5 months (range, 3-179 months), 66 PT patients had local recurrence (LR), and four patients had distant metastasis. The 1-, 3-, 5-, and 10-year RFS of the PT patients were 90.8%, 81.8%, 78%, and 76.7%, respectively. Age, fibroadenoma (FA) surgery history, treatment, mitotic activity, and surgical margin were selected as the independent factors for PT prognosis. The nomogram showed good discriminative ability and calibration, as indicated by the C-index [0.78, 95% confidence interval (CI): 0.75-0.11]. Conclusions: Independent predictors related to PT prognosis were selected to establish a nomogram for predicting the RFS of PT. This nomogram was able to objectively stratify PT patients into prognostic groups and performed well in the internal validation.

Contralateral prophylactic mastectomy for unilateral breast cancer in Chinese female population: a retrospective cohort study.

Background: Due to differences in socioeconomic and cultural backgrounds, the characteristics and prognosis of Asian female patients choosing contralateral prophylactic mastectomy (CPM) are likely to be different from Western patients. To fill the research gap of CPM in Asian populations, this study aims to explore the application trend, survival benefits, decision-making factors, and satisfaction of CPM based on the Chinese patients undergoing CPM. Methods: The 0-III stage unilateral breast cancer (UBC) patients who received breast surgery in the Chinese PLA General Hospital from 2005 to 2017 were selected. The surgical procedures included simple mastectomy (SM), nipple-sparing mastectomy (NSM), breast conserving surgery (BCS), and CPM. Cox proportional regression analyses and Kaplan-Meier (KM) curve were performed to compare the overall survival (OS) and disease-free survival (DFS) rates between CPM group and unilateral mastectomy (UM) group. Proportional propensity score matching (PSM) with a 1:1 ratio was used to match the two groups and secondary survival analysis was performed. Logistic regression models were used to test predictive factors related to patients' CPM surgical decision-making. Results: Four thousand two hundred and seventy-six patients were included in the study, with 73 patients receiving CPM, 3,567 receiving SM, 151 receiving NSM, and 485 receiving BCS. CPM surgery was first used in 2007, with a peak application rate of 3.02% in 2016. Three thousand seven hundred and ninety-one patients were included in the survival analysis, with a median follow-up time of 66.60 months. Compared to UM patients, neither the KM survival curve nor Cox regression hazard analyses of CPM showed better OS (P=0.963; P=0.834). After PSM, CPM also did not exhibit significant survival benefits in OS (P=0.335) and DFS (P=0.409). The logistic regression analyses showed that NSM surgery and lower tumor-node-metastasis (TNM) stage were independent factors to promote the CPM decision-making of patients. The CPM group showed high overall satisfaction (84.9%) and relatively low appearance satisfaction (69.9%). Conclusions: CPM was practiced for the first time since 2007 in our hospital. CPM does not provide any OS and DFS benefits compared to UM and the appearance satisfaction procedure was relatively low. Therefore, clinicians should fully communicate with patients before surgery and be more cautious in giving CPM recommendations.

Breast-conserving therapy versus mastectomy for breast cancer: a ten-year follow-up single-center real-world study.

Background: The rapid development of early diagnostic methods and systematic treatment for breast cancer have shed lights on the insight of prognosis of breast-conserving therapy versus mastectomy. However, there are relatively few studies with long-term follow-up, large patient cohort and under the contemporary setting in China on the subject of survival of patients undergoing breast conserving therapy versus mastectomy. Methods: Data on the cases of breast-conserving therapy and mastectomy for breast cancer from October 1, 2005 to September 31, 2010 were retrieved from the breast cancer database of Chinese PLA General Hospital. The clinicopathological characteristics of patients were compared by chi-square test or Fisher's exact test. Breast cancer-specific survival, disease-free survival, local recurrence-free survival, loco-regional recurrence-free survival, and distant metastasis-free survival were calculated and compared by Kaplan-Meier survival analysis and log-rank test firstly. And then Cox Proportional-Hazards model was used for multivariate analysis. Results: There were 296 patients in the breast-conserving surgery group and 675 patients in the mastectomy group. For patients with invasive breast cancer in the entire cohort, the 10-year breast cancer-specific survival rate of patients in the breast-conserving surgery group at stage I-II was significantly higher than that of the mastectomy group. However, surgical method was not an independent prognostic factor for breast cancer-specific survival, disease-free survival and local recurrence-free survival. Moreover, N stage and luminal B-like subtype were independent prognostic factors for the breast cancer-specific survival of invasive breast cancer in the entire cohort. Conclusions: This study suggests that there is no significant difference in breast cancer-specific survival between breast cancer patients undergoing breast-conserving surgery and mastectomy after adjusting for confounding factors. Lymph node staging is the major risk factor affecting patients' survival. In this case, choosing patients with smaller tumor size, avoiding patients with stage N3, and removing a smaller volume of breast tissue including tumors while ensuring negative margins may reduce the patient's risk of local recurrence and loco-regional recurrence.

Clinicopathological features and prognosis of bilateral breast cancer: a single-center cohort study based on Chinese data.

Background: The incidence of bilateral breast cancer (BBC) is low, accounting for 5% of patients with breast cancer. This study aimed to investigate the clinicopathological features and prognosis of synchronous bilateral breast cancer (SBBC) and metachronous bilateral breast cancer (MBBC) in the Chinese population. Methods: Patients with BBC, including SBBC and MBBC, were selected from 6,162 breast cancer patients who underwent surgery at the Chinese People's Liberation Army (PLA) General Hospital between January 2007 and December 2019. Furthermore, patients with unilateral breast cancer (UBC) who underwent surgery at the same time were randomly selected at a ratio of 1:2 as the control group. Clinicopathological features and prognosis were compared between the groups. Results: In all, 123 (2.0%) patients with BBC were enrolled in this study, including 98 (1.6%) SBBC and 25 (0.4%) MBBC patients. A total of 280 patients with UBC were selected for the control group. Compared with patients with UBC, patients with SBBC were more likely to be older and have a family history of breast cancer, non-infiltrative carcinoma, lower pathological tumor-node-metastasis (pTNM) stage, and luminal A type breast cancer as their first tumor. Patients with MBBC were more likely to be postmenopausal and have hormone receptor [estrogen receptor (ER)/progesterone receptor (PR)] negativity, a higher pTNM stage, and a triple-negative first tumor. Patients with UBC with ER/PR (-) were more likely to develop contralateral breast cancer (CBC) than those with ER/PR (+). There was no significant difference in overall survival (OS) and disease-free survival (DFS) between patients with SBBC and patients with UBC. Patients with MBBC had worse DFS than those with UBC, but OS was similar for both types of patients. Patients with MBBC <55 years at first diagnosis had significantly shorter DFS compared to those with SBBC and UBC. A multivariate Cox proportional hazards model revealed that age ≥55 years and ER/PR negativity of the first tumor were independent risk factors for OS. Independent risk factors for DFS included MBBC, age <55 years, family history of other malignant tumors, ER/PR (-), lymphovascular invasion, and N stage ≥2 of the first tumor. Conclusions: The OS and DFS of patients with SBBC and UBC were similar. The MBBC patients, especially those <55 years old at first diagnosis, had shorter DFS than patients with UBC.

External verification and improvement of the Neo-Bioscore staging system in a Chinese cohort.

Background: Accurately predicting outcomes for patients with breast cancer receiving neoadjuvant chemotherapy (NAC) is critical for clinical decisions. Prognostic models applicable to the Chinese population remain limited. The Neo-Bioscore staging system has been utilized as a predictive model for survival of breast cancer patients after NAC. This study aimed to validate the applicability of Neo-Bioscore in a Chinese population and develop an improved staging system based on it to predict prognosis of Chinese patients more accurately. Methods: This study retrospectively collected clinicopathological and survival data in patients receiving NAC from February 2005 to August 2018 in PLA General Hospital. Discrimination, calibration and clinical usefulness were used to assess model performance. Univariate and multivariate analyses assessed relationships between clinicopathological factors and disease-specific survival. For model modification, postoperative pathological staging in the Neo-Bioscore was substituted with the posttreatment pathological tumor (ypT) stage and posttreatment pathological lymph node (ypN) stage. Neo-Bioscore and Modified Neo-Bioscore were compared with the American Joint Committee on Cancer (AJCC) staging system. Results: A total of 436 patients with a median follow-up of 67 months were included. Five-year disease-specific survival (DSS), overall survival, and disease-free survival rates were 88.0%, 87.9%, and 76.8%, respectively. The concordance index (C-index) of the Neo-Bioscore staging system, posttreatment pathological stage (PS), and pretreatment clinical stage (CS) for DSS were 0.78 [95% confidence interval (CI): 0.72-0.83], 0.75 (95% CI: 0.69-0.82), and 0.68 (95% CI: 0.62-0.74), respectively. No significant difference between the Neo-Bioscore and PS was observed in the C-index (P=0.399). ypT and ypN were included in Neo-Bioscore to replace PS and create a modified staging system named MNeo-Bioscore. The C-index for DSS of the MNeo-Bioscore was 0.82 (95% CI: 0.78-0.87), and the calibration curve and decision curve analysis (DCA) curve performed well in internal validation. Conclusions: The Neo-Bioscore staging system provided precise prognostic stratification for Chinese breast cancer patients receiving NAC; ypN and ypT stage may be substituted for PS to add significant prognostic value for Neo-Bioscore.

Surgical management and prognosis of phyllodes tumors of the breast.

Background: Regardless of histological grade, phyllodes tumors (PTs) exhibit the potential of local recurrence. The National Comprehensive Cancer Network (NCCN) recommends wide local excision (WLE) with a 1 cm margin or more for borderline/malignant PTs but excisional biopsy for benign PTs. However, the treatment of benign PTs remains controversial and the clinicopathologic risk factors for the local recurrence is still unclear. Methods: We retrospectively analyzed 238 patients with PTs who underwent surgery at the Chinese PLA General Hospital from January 1, 2006 and April 30, 2020. We stratified our analysis according to histologic grade and explored the clinicopathologic factors to influence local recurrence (LR), including age, histologic grade, history of fibroadenoma, type of surgery [vacuum-assisted biopsy system (VABS), local excision (LE), wide local excision (WLE) and mastectomy]. Results: All 238 cases were categorized as benign (171, 71.8%), borderline (38, 16.0%), or malignant (29, 12.2%). The median follow-up was 50.2 months. In multivariate analysis, histologic grade (P<0.01) and history of fibroadenoma (P<0.01) were independent prognostic factors for LR. No difference existed in the recurrence rate of BPT treated with different surgical procedures (P=0.397), whereas a higher recurrence rate was found in VABS and LE subgroups than in WLE and mastectomy subgroups for borderline/malignant tumors (P<0.01). Conclusions: No association found between surgical modalities and LR rate for BPT. We suggested a "wait-and-watch" policy for patients with unexpected benign subtypes, instead of unnecessary re-excision. In addition, VABS or LE can be treated for BPT with small mass, whereas WLE or even mastectomy should be conducted for borderline/malignant PTs with large mass.

A simplified scoring protocol to improve diagnostic accuracy with the breast imaging reporting and data system in breast magnetic resonance imaging.

Background: The breast imaging reporting and data system (BI-RADS) lexicon provides a standardized terminology for describing leision characteristics but does not provide defined rules for converting specific imaging features into diagnostic categories. The inter-reader agreement of the BI-RADS is moderate. In this study, we explored the use of a simplified protocol and scoring system for BI-RADS categorization which integrates the morphologic features (MF), kinetic time-intensity curve (TIC), and apparent diffusion coefficient (ADC) values with equal weights, with a view to providing a convenient and practical method for breast magnetic resonance imaging (MRI) and improving the inter-reader agreement and diagnostic performance of BI-RADS. Methods: This cross-sectional, retrospective, single-center study included 879 patients with 898 histopathologically verified lesions who underwent an MRI scan on a 3.0 Tesla GE Discovery 750 MRI scanner between January 1, 2017, and June 30, 2020. The BI-RADS categorization of the studied lesions was assessed according to the sum of the assigned scores (the presence of malignant MF, lower ADC, and suspicious TIC each warranted a score of +1). Total scores of +2 and +3 were classified as category 5, scores of +1 were classified as category 4, and scores of +0 but with other lesions of interest were classified as category 3. The receiver operating characteristic (ROC) curves were plotted, and the sensitivity, specificity, and accuracy of this categorization were investigated to assess its efficacy and its consistency with pathology. Results: There were 472 malignant, 104 risk, and 322 benign lesions. Our simplified scoring protocol had high diagnostic accuracy, with an area under curve (AUC) value of 0.896. In terms of the borderline effect of pathological risk and category 4 lesions, our results showed that when risk lesions were classified together with malignant ones, the AUC value improved (0.876 vs. 0.844 and 0.909 vs. 0.900). When category 4 and 5 lesions were classified as malignant, the specificity, accuracy, and AUC value decreased (82.3% vs. 93.2%, 89.3% vs. 90.2%, and 0.876 vs. 0.909, respectively). Therefore, to improve the diagnostic accuracy of the protocol for BI-RADS categorization, only category 5 lesions should be considered to be malignant. Conclusions: Our simplified scoring protocol that integrates MF, TIC, and ADC values with equal weights for BI-RADS categorization could improve both the diagnostic performance of the protocol for BI-RADS categorization in clinical practice and the understanding of the benign-risk-malignant breast diseases.

Comparative healing of swine skin following incisions with different surgical devices.

BACKGROUND: Electrosurgical technology is widely used in surgical dissection and hemostasis, but the generated heat creates thermal injury to adjacent tissues and delays wound healing. The plasma blade (PB) applies pulsed radiofrequency (RF) to generate electrical plasma along the edge of a thin, flat, insulated electrode, minimizing collateral tissue damage. This study aimed to evaluate wound healing in swine skin following incision with a new surgical system that applies low-temperature plasma (NTS-100), a foreign PB, conventional electrosurgery (ES), and a scalpel blade. METHODS: In vitro porcine skin and an in vivo porcine skin model were used in this study. Full-thickness skin incisions 3 cm in length were made on the dorsum of each animal for each of the 5 surgical procedures at 0, 21, 28, 35, and 42 days. The timing of the surgical procedures allowed for wound-healing data points at 1, 2, 3, and 6 weeks accordingly. Local operating temperature and blood loss were quantified. Wounds were harvested at designated time points, tested for wound tensile strength, and examined histologically for scar formation and tissue damage. RESULTS: Local operating temperature was reduced significantly with NTS-100 (cut mode 83.12±23.55 °C; coagulation mode 90.07±10.6 °C) compared with PB (cut mode 94.46±11.48 °C; coagulation mode 100.23±6.58 °C, P<0.05) and ES (cut mode 208.99±34.33 °C, P<0.01; coagulation mode 233.37±28.69 °C, P<0.01) in vitro. Acute thermal damage from NTS-100 was significantly less than ES incisions (cut mode: 247.345±42.274 versus 495.295±103.525 µm, P<0.01; coagulation mode: 351.419±127.948 versus 584.516±31.708 µm, P<0.05). Bleeding, histological scoring of injury, and wound strength were equivalent for the NTS-100 and PB incisions. CONCLUSIONS: The local operating temperature of NTS-100 was lower than PB, and NTS-100 had similarly reliable safety and efficacy.

Inverted-T pattern reduction mammoplasty in bilateral breast ptosis: cosmetic and oncological outcomes.

BACKGROUND: Breast ptosis is directly caused by Cooper's ligament laxity, with the decline of nipple areola complex (NAC) and mammary parenchyma. Breast cancer with ptosis is always a knotty problem that can hardly be repaired by classic breast conservation surgery (BCS) ending up with a pleasing appearance. We analyzed our 12 years' experience of performing inverted-T pattern techniques to treat bilateral breast ptosis, with or without breast cancer. METHODS: One hundred forty-eight breasts in 74 patients undergoing inverted-T pattern reduction mammoplasty were included in this study. Information about patients' clinical and surgical characteristics, complications, NAC sensitivity, cosmetic and oncological outcomes were collected and retrospectively analyzed. RESULTS: In the cohort of 57 patients with pure breast ptosis, the mean body mass index (BMI) was 25.2 kg/m2, and the mean weight of resected tissue from the left and right breast reductions were 744.9 and 756.7 g. In the cohort of 17 patients diagnosed as breast cancer with ptosis, the mean BMI was 25.1 kg/m2, and the mean weight of resected tissue were 504.1 g for left and 535.6 g for right side. The majority of repairs were performed for tumors located in the upper outer (58.8%), mostly with inferior or superomedial pedicles (90%). All the upper inner tumors were repaired with inferior pedicles. Minor complications such as seroma (8.1%), NAC epidermolysis (8.1%), delayed wound healing (4.1%) were detected postoperatively. Partial NAC necrosis occurred in one patient (1.4%). 82.4% of all the patients rated "very satisfied" or "satisfied" as the final cosmetic outcomes. NAC sensitivity was "very high" and "high" in 82.4% patients. No local occurrence, distant metastasis and mortality occurred in tumor patients. CONCLUSIONS: The inverted-T pattern reduction mammoplasty is a reliable technique to treat bilateral breast ptosis with a low complication rate. For cases with breast cancer, this technique can achieve both satisfying cosmetic outcomes and oncological safety.

Advancement of prognostic models in breast cancer: a narrative review.

OBJECTIVE: To provide a reference for clinical work and guide the decision-making of healthcare providers and end-users, we systematically reviewed the development, validation and classification of classical prognostic models for breast cancer. BACKGROUND: Patients suffering from breast cancer have different prognosis for its high heterogeneity. Accurate prognosis prediction and risk stratification for breast cancer are crucial for individualized treatment. There is a lack of systematic summary of breast cancer prognostic models. METHODS: We conducted a PubMed search with keywords "breast neoplasm", "prognostic model", "recurrence" and "metastasis", and screened the retrieved publications at three levels: title, abstract and full text. We identified the articles presented the development and/or validation of models based on clinicopathological factors, genomics, and machine learning (ML) methods to predict survival and/or benefits of adjuvant therapy in female breast cancer patients. CONCLUSIONS: Combining prognostic-related variables with long-term clinical outcomes, researchers have developed a series of prognostic models based on clinicopathological parameters, genomic assays, and medical figures. The discrimination, calibration, overall performance, and clinical usefulness were validated by internal and/or external verifications. Clinicopathological models integrated the clinical parameters, including tumor size, histological grade, lymph node status, hormone receptor status to provide prognostic information for patients and doctors. Gene-expression assays deeply revealed the molecular heterogeneity of breast cancer, some of which have been cited by AJCC and National Comprehensive Cancer Network (NCCN) guidelines. In addition, the models based on the ML methods provided more detailed information for prognosis prediction by increasing the data dimension. Combined models incorporating clinical variables and genomics information are still required to be developed as the focus of further researches.

PCDHB17P/miR-145-3p/MELK/NF-κB Feedback Loop Promotes Metastasis and Angiogenesis of Breast Cancer.

Breast cancer is one of the most common life-threatening cancers, mainly because of its aggressiveness and metastasis. Accumulating evidence indicates that long non-coding RNAs (lncRNAs) participate in the development and progression of breast cancer. Nevertheless, the function and expression level of lncRNAs in breast cancer are still not fully understood. Here, we demonstrated that lncRNA PCDHB17P was up-expressed in human breast cancer tissues and cell lines. Knockdown of PCDHB17P remarkably suppressed migration and invasion, as well as tube formation ability of breast cancer cells. MiR-145-3p was significantly decreased in breast cancer samples, which was negatively correlated to the expression of PCDHB17P. In addition, we identified that MELK was a direct target gene of miR-145-3p, which was higher expressed in breast cancer tissues than that in adjacent normal tissues. Mechanistic investigation indicated that PCDHB17P acted as a cancer-promoting competing endogenous RNA (ceRNA) by binding miR-145-3p and upregulating MELK. Interestingly, MELK could in turn increase the promoter activity and expression of PCDHB17P via NF-κB, thus forming a positive feedback loop that drives the metastasis and angiogenesis of breast cancer. Overall, the results demonstrated that the constitutive activation of PCDHB17P/miR-145-3p/MELK/NF-κB feedback loop promotes the metastasis and angiogenesis of breast cancer, suggesting that this lncRNA might be a promising prognostic biomarker and therapeutic target for breast cancer.

Pulmonary sarcoidosis: from clinical features to pathology- narrative review.

Sarcoidosis is a multisystem disease with unknown causes. The prevalence of sarcoidosis that occurs worldwide is highly variable. It is pathologically characterized by the formation of non-necrotizing epithelioid cell granuloma, mainly affecting the respiratory tract and involving extrapulmonary organs including the skin, heart, extrathoracic lymph nodes, central nerves and eyes. A correct diagnosis of sarcoidosis depends on the clinical symptoms, imaging observations, and characteristic histopathological findings. This study aims to review the recent contributions of pulmonary sarcoidosis. It is based on a search of a published article and review on pulmonary sarcoidosis. PubMed, Embase and CNKI were searched for latest developments from 1977. The most common clinical symptoms of sarcoidosis include dry cough, dyspnea, and chest discomfort. The imaging manifestations of sarcoidosis can be divided into typical and atypical findings. Lymphadenopathy is a typical imaging manifestation of sarcoidosis. Sarcoidosis is also a highly variable multisystem disease with an unpredictable clinical course. Clinically encountered cases cover a wide range from asymptomatic patients with incidental findings in radiographic images to chronic progressive diseases. Corticosteroids are the most widely recommended as the first-line treatment for symptomatic or organ-threatening disease in sarcoidosis, but they are associated with substantial toxic effects. Meanwhile, for sarcoidosis, the follow-up is also an important part of the diagnosis and treatment. Pulmonary sarcoidosis needs further recognition. In this paper, the clinical features, imaging observations, pathology, and treatment modalities for pulmonary sarcoidosis are presented and discussed vis-à-vis the current dilemma in diagnosis and therapy.

Glutathione ethyl ester supplementation prevents airway hyper-responsiveness in mice.

BACKGROUND: Oxidative stress plays an important role in the pathogenesis of asthma. Glutathione (GSH) is considered to be one of the most important antioxidants. Our study systematically investigated the effect of the GSH alternative, glutathione ethyl ester (GSH-EE), on airway hyper-responsiveness (AHR) in mice. METHODS: Sixty-three male specific pathogen-free mice were used. Asthma was induced using a single dose of ovalbumin (OVA). The normal group (n=15) received vehicle only [Al(OH)3 in saline]. Then, 48 mice were divided into two groups, including a control group who received sodium phosphate buffer (pH =7.4), and the GSH-EE group who received 0.1% GSH-EE. AHR was measured 2, 6, and 12 hours after exposure to nebulized OVA (0.01%). The animals were then sacrificed, and lung tissue and the bronchi-alveolar lavage fluid (BALF) were harvested. Factors involved in the antioxidant response to asthma were then measured in these tissues, including thiol content (from GSH and protein), γ-glutamylcysteine synthetase (γ-GCS) activity and expression, and nuclear factor-erythroid-2-related factor (Nrf2) expression. RESULTS: The GSH-EE group showed a significant attenuation of AHR (P<0.01) 2 hours after OVA challenge, and significantly enhanced thiol contents by approximately 45% (P<0.05) at 2 and 6 hours after the last OVA challenge, compared to the control group. γ-GCS activity was also higher in the GSH-EE group compared to the control group at different time points (P<0.01). γ-GCSh and Nrf2 protein expression increased in the GSH-EE group and the control group compared with the normal group, but there was no statistically significant difference (P>0.05) between the GSH-EE group and the control group. CONCLUSIONS: GSH-EE supplementation can prevent AHR in asthmatic mice during the early stages. It may function by serving as a precursor for GSH biosynthesis and by protecting sulfhydryl groups from oxidation.

Snail promotes the generation of vascular endothelium by breast cancer cells.

A further understanding of tumor angiogenesis is urgently needed due to the limited therapeutic efficacy of anti-angiogenesis agents. However, the origin of endothelial cells (EC) in tumors remains widely elusive and controversial. Snail has been thoroughly elucidated as a master regulator of the epithelial-mesenchymal transition (EMT), but its role in endothelium generation is not yet established. In this study, we reported a new and unexpected function of Snail in endothelium generation by breast cancer cells. We showed that high Snail-expressing breast cancer cells isolated from patients showed more endothelium generated from these cells. Expression of Snail was positively correlated with endothelial markers in breast cancer patients. The ectopic expression of Snail induced endothelial marker expression, tube formation and DiI-AcLDL uptake of breast cancer cells in vitro, and enhanced tumor growth and microvessel density in vivo. Snail-mediated endothelium generation depended on VEGF and Sox2. Mechanistically, Snail promoted the expression of VEGF and Sox2 through recruiting the p300 activator complex to these promoters. We showed the dual function of Snail in tumor initiation and angiogenesis in vivo and in vitro through activation of Sox2 and VEGF, suggesting Snail may be an ideal target for cancer therapy.

Clinical features, prognosis, and influencing factors of contralateral prophylactic mastectomy in 58 patients with breast cancer.

BACKGROUND: The past two decades have witnessed the increasing application of contralateral prophylactic mastectomy (CPM) for women with breast cancer in the western countries. Over 30% of young patients choose to underwent CPM up to 2015. However, the adoption rate of CPM has not shown a remarkably increasing in Asian countries. In China, only a few centers have introduced CPM, and no relevant literature has been published. In this study, we look forward to identify the clinical features and prognostic factors of women who underwent CPM in our hospital, to inform decision-making processes for both doctors and patients. METHODS: The clinical data of 58 eligible patients were retrospectively analyzed. Intergroup comparisons were based on independent samples t-test and chi square test. The 5-year disease-free survival (DFS) and overall survival (OS) were obtained by using life tables, and factors affecting the survivals were analyzed by using the Kaplan-Meier method. RESULTS: The mean age of these women was 40.14±11.17 years, with 30 patients (51.7%) being ≤40 years; 13 patients (22.4%) had a family history of breast cancer; and 49 (69.0%) had known risk factors for breast cancer. The median follow-up period was 66.77 months, the 5-year OS was 89% and the 5-year DFS was 74%. The average age of onset was 41.53 (±10.964) in the disease-free survival group and 34.18 (±10.4) years in the recurrence/metastasis group, and t-test revealed a significant difference in the average age between these two groups (P=0.049). Chi-square test showed that the disease progression rate significantly differed among the different age subgroups and among subjects with different body mass index (BMI) (all P≤0.05). Moreover, surgical procedure, family history of breast cancer, and some other factors showed no significant correlation with disease progression (all P>0.05). Kaplan-Meier survival analysis and log rank test further confirmed the above findings. CONCLUSIONS: The majority of patients who choose CPM are young and with known risk factors for breast cancer. Part of the young patients (≤40 years of age) are at a higher risk of disease progression.

A direct immunohistochemistry (IHC) method improves the intraoperative diagnosis of breast papillary lesions including breast cancer.

AIMS: The goal of this study is to evaluate a novel direct immunohistochemistry staining method on frozen tissues for the intraoperative diagnosis of breast papillary lesions. METHODS AND RESULTS: Keratin 5 (CK5) and smooth muscle myosin heavy chain (SMMHC) antibodies were labeled with horseradish peroxidase polymers and used for direct immunohistochemistry (IHC) staining on frozen sections of breast tissues during surgical operations. The results from direct IHC on 102 cases of breast papillary lesions were compared with those obtained by the conventional staining method on formalin-fixed paraffin-embedded tissues (FFPE). Compared to the conventional method, direct IHC staining can significantly improve the accuracy of intraoperative diagnosis of breast papillary lesions from 70% to 97% (p < 0.01). No false negative cases were found with direct IHC in this study. In comparison, 53% of cases with the conventional method were found false negative. Direct IHC also significantly reduced the deferred diagnosis rate from 21% to 3% (p < 0.01). Furthermore, the entire procedure of direct IHC can be finished within 10 minutes, which makes it more feasible for the use of intraoperative frozen section diagnosis. CONCLUSION: The direct IHC staining method can significantly improve the efficiency and accuracy of intraoperative diagnosis of breast papillary lesions. It also fits better for the quick turnaround time required for intraoperative diagnosis.

A Novel Anti-EGFR mAb Ame55 with Lower Toxicity and Better Efficacy than Cetuximab When Combined with Irinotecan.

To improve efficacy and minimize toxicity of EGFR inhibition treatment, we developed Ame55, a novel anti-EGFR IgG1 with lower affinity to EGFR than cetuximab (C225) from a human phage library. Ame55 had lower bioactivity than cetuximab in vitro but similar antitumor efficacy as cetuximab in vivo. Moreover, Ame55 was more efficacious than cetuximab in a Lovo cell xenograft tumor model when combined with irinotecan (CPT-11). Ame55 concentrates in the mouse xenograft tumor and has less toxicity than cetuximab in cynomolgus monkeys in an overdose study.

The role of magnetic resonance imaging in detection and surgical treatment of breast intraductal papillomas.

BACKGROUND: Intraductal papillomas are discrete benign tumors of the breast duct epithelium. Due to the risk of subsequent carcinoma, a surgical excision is generally recommended as a precaution. However, it is difficult to initially diagnose and accurately locate the lesions both in pre-surgery and surgery periods. METHODS: Retrospectively analyzed 245 patients, with a pathologically proven breast intraductal papillomas. All the patients underwent magnetic resonance imaging (MRI) scans and ultrasound examination(s) pre-surgery and/or in surgery. All the patients who underwent surgery were divided into four groups according to the following operation method type(s): ultrasound & clinical examination excision, methylene blue notation excision, methylene blue notation & MRI guide excision, and MRI guide excision. Then, the differences between the last two MRI guide excisions and the first two conventional methods were analyzed. Afterwards, 238 patients were followed up for recurrence checks. SPSS 19.0 statistical software was used and the results of P<0.05 being considered statistically significant. RESULTS: A total of 161 (65.7%) and 48 (19.6%) patients were pathological diagnosed of solitary and multiple papilloma separately, and 36 (14.7%) patients had papillomatosis; 168 and 243 cases with positive signs, which were detected in all 245 patients who had underwent ultrasound and MRI examination(s), with the detection rate being 68.6% and 99.0% respectively. MRI imaging could clearly present mass-like lesions (solitary and multiple mass) and non-mass like lesions (ductal and regional). Whereas, ultrasound imaging could barely show mass-like (solitary and multiple mass) lesions. In surgery, when compared with traditional methods, MRI imaging could also more accurately locate the lesions and guide the excision. MRI guidance is both applicable to patients with and without nipple discharge, in addition to those who show no abnormal signs in ultrasound imaging. The recurrence-free survival time with traditional surgery methods was significantly lower than those in the MRI guide groups. CONCLUSIONS: MRI is accurate at the detection, localization and resection range of intraductal papilloma lesions; all capabilities which are critical to successful breast surgery.

Kindlin-2 could influence breast nodule elasticity and improve lymph node metastasis in invasive breast cancer.

This study investigated the relationship between quantitative parameters of shear wave elastography (SWE, maximum elasticity [Emax], minimum elasticity [Emin], mean elasticity [Emean]), collagen intensity and Kindlin-2 expression in benign and malignant breast nodules, and if Kindlin-2 expression is related with lymph node metastasis. A total of 102 breast nodules from 102 patients were included in our study who underwent ultrasound elastography before surgery or core needle biopsy. There was a significant difference between benign and malignant breast nodules in Emax, Emean, collagen intensity and Kindlin-2 expression, but it had no difference in Emin. Collagen intensity and Kindlin-2 expression both correlated positively with Emax, but not with Emean. Among 38 malignant breast nodules, the average Emax of the metastasis group was higher than that of the non-metastasis group, but it had no statistical significance. Compared with the non-metastasis group, Kindlin-2 expression was considerably higher in the metastasis group. However, there was no difference in collagen intensity between the metastasis group and the non-metastasis group. In conclusion, Kindlin-2 and collagen might contribute to breast nodule elasticity through molecular mechanisms. In breast cancer, overexpression of Kindlin-2 might be a risk factor for lymph node metastasis.

Application of immediate breast reconstruction with silicon prosthetic implantation following bilateral mammary gland excision in treatment of young patients with early breast cancer.

OBJECTIVE: To evaluate the application of immediate breast reconstruction (IBR) with silicon prosthetic implantation following bilateral nipple-preserving subcutaneous mammary gland excision in the treatment of young patients with early breast cancer. METHODS: We retrospectively analyzed the clinical data of 21 patients with breast cancer who were performed on IBR following bilateral nipple-preserving subcutaneous mammary gland excision in our hospital from January 2006 to March 2011. RESULTS: The operations were successful in all the 21 patients. Also, the treatment provided a good cosmetic effect. No local recurrence or distant metastasis was found in these 21 patients during the 6-66-month follow-up. CONCLUSIONS: For the young patients with early breast cancer, mammary gland excision on the affected side along with prophylactic excision of the contralateral side, namely IBR following bilateral nipple-preserving subcutaneous mammary gland excision, provides good clinical effectiveness and cosmetological effects.