Malignant Breast Disease Research Articles

Breast cancer prediction model based on clinical and biochemical characteristics: clinical data from patients with benign and malignant breast tumors from a single center in South China.

Breast cancer is the most prevalent cancer and is second leading cause of death from malignancy among women worldwide. In addition to tumor factors, the host characteristics of tumors have been paid more and more attention by the medical community. This study aimed to develop a breast cancer prediction model for the Chinese population using clinical and biochemical characteristics. This is a retrospective study. From 2012 to 2021, we selected 19,751 patients with breast diseases from the Guangdong Hospital of Traditional Chinese Medicine, which included 5660 patients with breast cancer and 14,091 patients with benign breast diseases-75% of patients were randomly assigned to the training group and 25% to the test group using a total of 34 clinical and biochemical characteristics. Significant clinical signs were investigated, and logistic regression with recursive feature elimination (RFE) model was used to develop a prediction model for distinguishing benign from malignant breast diseases. The prediction model's accuracy, precision, sensitivity, specificity, and area under the ROC curve (AUC) were calculated. Clinical statistics demonstrated that the prediction model comprised 19 clinical characteristics had statistical separability in both the training group and the test group, as well as good sensitivity and prediction. This model based on biochemical parameters demonstrates a significant predictive effect for breast cancer and may be useful as a reference for invasive tissue biopsy in patients undergoing BI-RADS 3 and 4A breast imaging.

Lactation Education for Surgeons: American Society of Breast Surgeons (ASBrS) Survey Demonstrates Strong Member Interest in Expanded Training.

The availability and extent of breastfeeding-specific surgical training has not been previously described. We aimed to survey breast surgeons on their lactation education and desire for additional knowledge. Members of the American Society of Breast Surgeons were invited via email to anonymously complete an electronic survey from 27 October 2021 to 23 January 2022. The survey content included demographic information, sources of lactation education, and desired topics and methods for further training. Descriptive statistics were used to analyze the data. A total of 2698 surveys were delivered and 542 (20.1%) completed. While nearly all respondents (99%) reported treating lactating patients at least once or twice per year, 78% reported that their training was inadequate. The most frequently cited sources of lactation information were peer-to-peer informal knowledge sharing (50%) and personal experience with breastfeeding (44%). Nearly all respondents (99%) agreed that formal lactation education would benefit breast surgeons. Specific topics of interest included management of patients with complications of lactation (48%), management of lactating patients with a new diagnosis of breast cancer (47%), and counseling patients with pregnancy-associated breast cancer who desire to breastfeed (46%). The most frequently recommended educational formats included presentation at a national conference (60%), evidence-based management guidelines (58%), webinar (55%), and workshop/course (47%). Breast surgeons self-report minimal formal training in the management of benign and malignant breast disease in lactating patients and strong desire for expanded education. Development of clinical practice guidelines and additional educational content for surgeons should be considered to meet the needs of this patient population.

Sentinel Lymph Node Detection in Breast Cancer: An Innovative Technique.

(1) Background: Sentinel lymph node biopsy is important in the search for metastases, especially in patients with malignant breast disease. Our study proposed new techniques to prevent complications such as possible postoperative seroma formation, pain or hypoesthesia of the axillary cord and medial arm surface, as well as motor deficits, to avoid disabling outcomes and presents initial data from our experience with the sentinel lymph node biopsy technique. (2) Methods: We mainly used two radioactive tracer detection techniques and a new technique using a radiotracer called Sentimag-magtrace. The positive lymph node was located and removed to perform histologic analysis. In our study, we evaluate 100 patients who underwent breast cancer surgery. (3) Results: We calculated the identification rates of the different methods of sentinel lymph node detection and found that it was 88.9% using radioactive tracers vs. 89.5% using the magnetic tracer technology (Sentimag). (4) Conclusions: Thus, this technique avoids radiation exposure for both patients and health care providers, and can reduce costs and time.

DOG-1 as a Myoepithelial Marker in Discriminating Invasive Breast Carcinomas From Non-Invasive Breast Lesions.

Introduction The most common cancer in women is, by far, breast cancer. The incidence and mortality of breast cancer must be reduced by a multidisciplinary strategy that includes education campaigns, preventive measures, screening programmes for early diagnosis, and the availability of treatment facilities. The use of immunohistochemical (IHC) stains with relative specificity for myoepithelial markers has become a mainstay of standard diagnostic breast pathology because the presence and distribution of myoepithelial cells might differ greatly amongst the distinct breast proliferation. Although it has also been reported that DOG1 is expressed in other mesenchymal tumours, DOG1 has been demonstrated to be sensitive and specific for the detection of gastrointestinal stromal tumors (GISTs). Both myoepithelial cells (MECs) and luminal epithelial cells have occasionally displayed DOG1 immunoreactivity in the breast. Materials and methods This prospective cross-sectional study was done in the Department of Pathology at Osmania General Hospital, Hyderabad on 60 cases from June 2017 to June 2019. Female patients with different breast lesions including benign proliferating lesions, ductal carcinoma in-situ (DCIS), and invasive carcinoma breast cases were included in the study.Inflammatory lesions, mesenchymal, and metastatic tumors were excluded.IHC expression of DOG1 as a myoepithelial marker to discriminate invasive from non-invasive breast lesions was evaluated and correlated withclinicopathological features. Results The mean age of the study population was 33.67 ± 8.48 in the benign group and 54.43 ± 12.84 in the malignant group. Fifty percent (15) of the patients with benign lesions belonged to the age group 20-30 years, whereas 26.7% (8) of the patients with malignant lesions belonged to the age group 61-70 years. DOG-1 expression was strongly positive in fibroadenoma, ductal hyperplasia, fibrocystic disease, whereas strongly negative in malignant disease of the breast (p< 0.0001). P63 expression was strongly positive in benign breast diseases and strongly negative in malignant diseases (p< 0.0001). Conclusion DOG1 seems to be similar to p63 as a myoepithelial cell marker both in normal breast tissue and in benign lesions. DOG1 is strongly positive in benign breast diseases and strongly negative in malignant breast diseases. Hence, it can be consideredas a useful myoepithelial marker in differentiating invasive breast carcinoma and non-invasive breast lesions.

To Study the Effectiveness of Mofified Triple Test Score in Differentiating Benign Versus Malignant Breast Diseases

To Study the Effectiveness of Mofified Triple Test Score in Differentiating Benign Versus Malignant Breast Diseases

Radiomics Analysis of Breast Lesions in Combination with Coronal Plane of ABVS and Strain Elastography.

Breast cancer is the most common tumor globally. Automated Breast Volume Scanner (ABVS) and strain elastography (SE) can provide more useful breast information. The use of radiomics combined with ABVS and SE images to predict breast cancer has become a new focus. Therefore, this study developed and validated a radiomics analysis of breast lesions in combination with coronal plane of ABVS and SE to improve the differential diagnosis of benign and malignant breast diseases. 620 pathologically confirmed breast lesions from January 2017 to August 2021 were retrospectively analyzed and randomly divided into a training set (n=434) and a validation set (n=186). Radiomic features of the lesions were extracted from ABVS, B-ultrasound, and strain elastography (SE) images, respectively. These were then filtered by Gradient Boosted Decision Tree (GBDT) and multiple logistic regression. The ABVS model is based on coronal plane features for the breast, B+SE model is based on features of B-ultrasound and SE, and the multimodal model is based on features of three examinations. The evaluation of the predicted performance of the three models used the receiver operating characteristic (ROC) and decision curve analysis (DCA). The area under the curve, accuracy, specificity, and sensitivity of the multimodal model in the training set are 0.975 (95% CI:0.959-0.991),93.78%, 92.02%, and 96.49%, respectively, and 0.946 (95% CI:0.913 -0.978), 87.63%, 83.93%, and 93.24% in the validation set, respectively. The multimodal model outperformed the ABVS model and B+SE model in both the training (P < 0.001, P = 0.002, respectively) and validation sets (P < 0.001, P = 0.034, respectively). Radiomics from the coronal plane of the breast lesion provide valuable information for identification. A multimodal model combination with radiomics from ABVS, B-ultrasound, and SE could improve the diagnostic efficacy of breast masses.

The Ratio of Monocyte to Apolipoprotein A1 is an Independent Predictor of Breast Cancer: A Retrospective Study.

To explore the predictive value of the ratio of monocyte to apolipoprotein A1 (MAR) (a new index related to inflammation and lipid in breast cancer (BC)) and its relationship with clinicopathological staging. The hematological test results of 394 patients with breast diseases, including 276 cases of BC, 118 cases of benign breast disease (BBD), and 219 healthy volunteers (HV), were retrospectively collected. The clinical value of MAR was analyzed with binary logistic regression. Using statistical software analysis, the results showed that MAR level (P<0.001) was the largest in the BC group, followed by BBD, and the lowest in the HV group, and it was found to be an indicator to distinguish BC from BBD, also an independent risk factor for BC. The increase in MAR level showed that the risk of BC was 3.733 times higher than that of HV (P<0.001). In addition, there was a notable difference in MAR between early, middle and late stages of BC patients (P=0.047), with the highest MAR level in late stage (0.510±0.078) and the lowest MAR level in early stage (0.392±0.011); the MAR level of those with tumor invasion depth of Phase 4 was the highest (0.484±0.072), and that of Phase 1/2 was the lowest (0.379±0.010), with a statistically significant difference (P<0.001). MAR was positively correlated with tumor invasion depth (P<0.001, r=0.210), that's, the size of MAR increased when there was more deeper tumor invasion. MAR is a new indicator for the auxiliary differential diagnosis of benign and malignant breast diseases, and is also an independent risk factor for BC. High-level MAR is closely related to late staging and tumor invasion depth of BC. It can be seen that MAR is a potentially valuable predictor of BC, and this is the first study to explore the clinical value of MAR in BC.

Potential Early Markers for Breast Cancer: A Proteomic Approach Comparing Saliva and Serum Samples in a Pilot Study.

Breast cancer is the second leading cause of death for women in the United States, and early detection could offer patients the opportunity to receive early intervention. The current methods of diagnosis rely on mammograms and have relatively high rates of false positivity, causing anxiety in patients. We sought to identify protein markers in saliva and serum for early detection of breast cancer. A rigorous analysis was performed for individual saliva and serum samples from women without breast disease, and women diagnosed with benign or malignant breast disease, using isobaric tags for relative and absolute quantitation (iTRAQ) technique, and employing a random effects model. A total of 591 and 371 proteins were identified in saliva and serum samples from the same individuals, respectively. The differentially expressed proteins were mainly involved in exocytosis, secretion, immune response, neutrophil-mediated immunity and cytokine-mediated signaling pathway. Using a network biology approach, significantly expressed proteins in both biological fluids were evaluated for protein-protein interaction networks and further analyzed for these being potential biomarkers in breast cancer diagnosis and prognosis. Our systems approach illustrates a feasible platform for investigating the responsive proteomic profile in benign and malignant breast disease using saliva and serum from the same women.

Same Day Discharge After Mastectomy and Immediate Implant-Based Breast Reconstruction: A Retrospective Cohort Comparison Using the National Surgical Quality Improvement Program Database.

Currently, overnight admission after immediate implant-based breast reconstruction (IBR) is the standard of care. Our study aims to analyze the safety, feasibility, and outcomes of immediate IBR with same-day discharge as compared with the standard overnight stay. The 2015-2020 National Surgical Quality Improvement Program database was reviewed to identify all patients undergoing mastectomy with immediate IBR for malignant breast disease. Patients were stratified into study (patients discharged day of surgery) and control (patients admitted after surgery) groups. Patient demographics, comorbidities, surgical characteristics, implant type, wound complications, readmission, and reoperation rates were collected and analyzed. Univariate and multivariate logistic regression was used to determine independent predictors of same-day discharge versus admission. In addition, Pearson χ2 test was used for comparison of proportions and t test was used for continuous variables unless distributions required subsequent nonparametric analyses. Statistical significance was defined as a P value less than 0.05. A total of 21,923 cases were identified. The study group included 1361 patients discharged same day and the control group included 20,562 patient s admitted for average of 1.4 days (range, 1-86). Average age was 51 years for both groups. Average body mass index for the study group 27 and 28 kg/m2 for the control group, respectively. Total wound complication rates were similar (4.5% study, 4.3% control, P = 0.72). Reoperation rates were lower with same-day discharge (5.7% study, 6.8% control, P = 0.105), though not statistically significant. However, same-day discharge patients had a significantly lower readmission rate compared with the control (2.3% study, 4.2% control, P = 0.001). National Surgical Quality Improvement Program data analysis over a 6-year period reveals that immediate IBR with same-day discharge is associated with a significantly lower readmission rate when compared with the standard overnight stay. The comparable complication profiles show that immediate IBR with same-day discharge is safe, potentially benefiting both patients and hospitals.

Nuclear Deformability of Breast Cells Analyzed from Patients with Malignant and Benign Breast Diseases.

Breast cancer is a heterogeneous and dynamic disease, in which cancer cells are highly responsive to alterations in the microenvironment. Today, conventional methods of detecting cancer give a rather static image of the condition of the disease, so dynamic properties such as invasiveness and metastasis are difficult to capture. In this study, conventional molecular-level evaluations of the patients with breast adenocarcinoma were combined with in vitro methods on micropatterned poly(methyl methacrylate) (PMMA) biomaterial surfaces that deform cells. A correlation between deformability of the nuclei and cancer stemness, invasiveness, and metastasis was sought. Clinical patient samples were from regions of the breast with different proximities to the tumor. Responses at the single-cell level toward the micropatterned surfaces were studied using CD44/24, epithelial cell adhesion marker (EpCAM), MUC1, and PCK. Results showed that molecular markers and shape descriptors can discriminate the cells from different proximities to the tumor center and from different patients. The cells with the most metastatic and invasive properties showed both the highest deformability and the highest level of metastatic markers. In conclusion, by using a combination of molecular markers together with nuclear deformation, it is possible to improve detection and separation of subpopulations in heterogenous breast cancer specimens at the single-cell level.

Pattern of Various Male Breast Diseases in a Tertiary Care Centre of Aurangabad District, Maharashtra, India- A Prospective Interventional Study

Introduction: A small percentage of men are affected by breast diseases and awareness of male breast disease is less and presentation is often delayed due to embarrassment. The most common presentation is gynaecomastia, where cosmetic correction is sought. Over the last two decades the rate of male breast complaints increased from 0.8% to 2.4%, while 1% of all breast cancer occur in males. Aim: To study the pattern of various male breast diseases in a tertiary care centre of Aurangabad District in Maharashtra, India. Materials and Methods: This prospective clinical interventional study was carried out in 44 male patients above age of 12 years coming with complaints related to breast to Department of General Surgery of Government Medical College, Aurangabad from 1st August 2017 to 31st July 2019. Detailed history was taken and any underlying causative disease/risk factor or medication if any was noted. Thorough clinical examination and laboratory investigations were done. Ultra-sonography of breast was done in all patients. Mammography was done in three patients who were having clinical suspicion of malignancy. Continuous variables were presented as mean, Standard Deviation (SD) or median if the data is unevenly distributed. Categorical variables are expressed as absolute numbers and percentages. Data was analysed using Statistical Package for the Social Sciences (SPSS) version 17.0. Results: The youngest patient was 12 years old and eldest was 85 years old. In the present study, 38 benign and 6 malignant male breast diseases were diagnosed. Out of total, 33 had gynaecomastia, 2 had breast abscess, 5 Infiltrating duct carcinoma and 1 each of mastitis, eczema of nipple, sebaceous cyst of areola and primary breast sarcoma. Out of 44 patients, 12 patients underwent surgery for benign and malignant breast diseases, 24 patients of gynaecomastia were managed by reassurance, 5 males with infiltrating ductal carcinoma were managed by modified radical mastectomy and 3 patients by medical therapy. Conclusion: It was concluded that benign male breast diseases were more common and ultrasound together with mammography should be used to differentiate characteristics of benign and malignant male breast lesions.

Mastalgia and associated breast diseases in a tertiary care center, Tamil Nadu: A cross-sectional study

Background: Mastalgia is the common breast condition among women. Mastalgia has highly variable prevalence which ranges 41–79%. It is more common in age group between 30 and 50 years. Mastalgia is approached according to its classification into three major categories, that is, cyclical pain, non-cyclical pain, and extra mammary pain. Breast pain ranges from mild to severe influencing the lifestyle of women affecting sexual relations, sleep pattern, and decreasing their daily life activities. Aim and Objectives: The aim of the study was to determine the incidence of benign and malignant breast disease in mastalgia. Materials and Methods: This cross-sectional study was conducted in Government Medical College, Sivagangai. Patients complaining of breast pain were examined. The data were compiled in an Excel worksheet, Epiinfo version 7.0 was used to analyze the data. Results: In our study, 100 patients complaining of breast pain were examined ranging from age 18 to 68 years. The mean age of the study population was 37.54 years and standard deviation of 9.077. Among 100 patients with mastalgia only 1 (1.64%) had malignancy which is insignificant and among rest 99 patients with mastalgia, 60.61% had benign breast diseases and 39.39% had no any breast lesions. Benign breast diseases are more commonly found in patients with mastalgia. Conclusion: Women having mastalgia can be reassured and some lifestyle modifications may aid the women. Hence, early detection of any breast disease in women having mastalgia and treating accordingly has considerable importance. Lifestyle modifications are needed in patients with mastalgia and they should come to facility to check and identify the issues and solve soon.

Diagnostics Role of Haematological Parameters in Benign and Malignant Breast Lesions: A Retrospective Observational Study from a Tertiary Healthcare Centre in Tamil Nadu, India

Introduction: Breast cancer is the most common malignancy diagnosed in women, and despite advancements in diagnosis and treatment, it still leads to significant morbidity and mortality. Distinguishing between benign and malignant breast disease is clinically challenging, and there is currently no serum biomarker available for early breast cancer detection. As part of the preoperative work-up for breast lesions, a Complete Blood Count (CBC) analysis is typically performed. Aim: This study aimed to evaluate the utility of CBC parameters in diagnosing malignant breast lesions and to analyse the diagnostic role of haematological parameters within benign and malignant breast lesions, as well as different histological breast cancer stages. Materials and Methods: This retrospective observational study was conducted for one year, from January to December 2021, at the Department of Pathology of PSG Institute of Medical Sciences and Research in Coimbatore, Tamil Nadu, India. The study included 60 female patients with both benign and malignant breast lesions. Histopathological examination confirmed the diagnoses of these lesions. CBC parameters, including haemoglobin, Total White Cell Count (TWBC), neutrophil count, lymphocyte count, monocyte count, platelet count, and Mean Platelet Volume (MPV), were collected from a total of 120 cases. Additionally, the Neutrophil-Lymphocyte Ratio (NLR), MonocyteLymphocyte Ratio (MLR), and Platelet-Lymphocyte Ratio (PLR) were calculated from the obtained CBC parameters for all cases. The values were expressed as mean and standard deviation, and an independent t-test was used to compare the two groups. A p-value less than 0.05 was considered significant. Results: Malignant breast lesions showed a significant increase in neutrophils (64.1±8.4%) and a significant decrease in lymphocytes (25.9±8%) and MPV (7.6±0.76 pg) compared to benign breast cases. The calculated ratios, such as NLR (2.9±1.7), MLR (0.32±0.2), and PLR (14.4±8), were also found to be increased in malignant cases. However, there were no significant variations in CBC parameters across the various stages of breast malignancy. Conclusion: Among the CBC parameters evaluated, neutrophil count, lymphocyte count, MPV, NLR, MLR, and PLR were significantly altered in breast malignancy compared to benign breast masses. Measuring CBC parameters and their derived ratios are fast, simple, inexpensive, and readily available method that can assist physicians in predicting breast malignancy.

Identification of Risk Factors for Mastalgia and Its Relationship with Benign or Malignant Breast Diseases.

Mastalgia is a medical condition that primarily affects women of all age groups. Affected individuals experience excruciating pain, tightness, or a burning sensation in the breast tissue. The aim of this study is to observe the clinicopathologic features of women with mastalgia and compare these features with asymptomatic cases. A total of 524 female patients who applied to the general surgery outpatient clinic were prospectively evaluated. The patients were divided into two groups. Group 1 (G1) included patients with mastalgia, while Group 2 (G2) included asymptomatic patients. The two groups were compared in terms of clinical, radiological, and pathological features. This study was conducted on 524 women, among whom the prevalence of mastalgia was found to be 61.45%. There were 322 patients in G1 and 202 patients in G2. The mean age was significantly higher in G2 compared to G1 (46.33±10.33 vs. 43.58±10.33, respectively; p=0.001). Premenopausal women rates for G1 and G2 were 73.91% and 59.4%, respectively (p=0.001). The regular exercise rate in G1 was 18.01%, while it was 25.74% in G2 (p=0.034). The past history of breast cancer rate was significantly higher in G2 than in G1 (p=0.015). The consumption of analgesics was significantly lower in G2 compared to G1 (p=0.05). Non-steroidal anti-inflammatory drugs were the most commonly used analgesic drug class in both groups, with significant intergroup differences (G1: 27.63%, G2: 19.8%, p=0.043). Screening mammography with or without ultrasound examination was performed significantly more often in G2 compared to G1 (66.33% vs. 55.27% and 82.17% vs. 72.98%, p=0.012 and p=0.016, respectively). No significant difference was found concerning the frequency of benign or malignant pathologies between the groups. Breast pain is common and should be considered physiological without other breast symptoms and after excluding non-breast causes. It is safe to provide symptom control advice and reassurance to patients who have breast pain but do not have signs or symptoms indicating a possible serious underlying condition requiring further medical intervention.

Bone Marrow Mesenchymal Stem Cells Restrain the Migration and Invasion of Breast Cancer Cells by Up-Regulating miR-2158 and Inactivating RAI2/NLRP3 Pathway

Exosomes are the key mediator for intercellular communication and participate in malignancies. Short non-coding RNAs derived from BMSCs-originated exosomes (BMSCs-exosomes) can be employed as biomolecules for tumor treatment. Here to we aim to dissect the function of microRNA-2158 from BMSCs-exosomes in breast malignant disease. Breast malignant cells received a separated transfection of miR-2158-mimics and miR-2158-inhibitor, and also treated with BMSCoriginated exosomes followed by analysis of cell viability by MTT method, cell invading and migrating capabilities via Transwell assays and protein levels of EMT-related and RAI2/NLRP3-related proteins by Western-blot. Breast cancer cells exhibited a significantly enhanced miR-2158 expression after transfection with miR-2158-mimics or treatment with BMSC-EXO, while it was reduced by miR-2158-inhibitor. As the miR-2158 was up-regulated, a significant impediment of proliferation and migration was denoted, along with a down-regulation of RAI2/NLRP3 signal transduction pathway and a retarded EMT process. Furthermore, cell proliferating and migrating capabilities were strengthened by miR-2158-inhibitor, together with an enhanced RAI2/NLRP3 signal and a strengthened EMT process. In conclusion, miR-2158 retarded the in vitro proliferating and migrating activities of breast malignant cells, leading to the inactivation of RAI2/NLRP3 signal transduction pathway, thereby exerting its tumor-suppressing function.

Взаимодействие внеклеточных ловушек нейтрофилов и антифосфолипидных антител у онкологических больных

Activation of NETosis processes has been detected in numerous autoimmune and non-autoimmune diseases with increasing concentrations of antiphospholipid antibodies (APA). Neutrophil extracellular traps (NETs) are an important activator of the coagulation cascade and an integral component of arterial and venous clots in cancer patients. Therefore, APA and NETs may be the links in the pathogenesis of thrombosis in cancer patients. Objective. To evaluate the severity of NETosis, hemostatic system activation and APA circulation (anti-β2-glycoprotein 1 (anti-β2-GPI)) in cancer patients. Design. A prospective controlled interventional non-randomized study. Patients and methods. This study included 144 patients who were divided into two groups: the study group – 111 patients aged 34–72 years with malignant breast and gynecological diseases of stages I–III (endometrial cancer, n = 25; ovarian cancer, n = 36; cervical cancer, n = 17; breast cancer, n = 33), and the control group – 33 healthy women. Prior to therapy, serum concentrations of NETosis markers – citrullinated histone H3 (citH3) and human myeloperoxidase antigen (MPO:Ag), markers of hemostatic activation (D-dimer and thrombin-antithrombin complex), and anti-β2-GPI antibodies were assessed. Results. Anti-β2-GPI antibodies were significantly more common in patients with ovarian cancer compared to controls. A significant correlation between the circulation of anti-β2-GPI and the concentration of MPO:Ag was also detected in these patients. All patients in the study group showed a significant increase in the markers of NETosis and hemostatic activation compared to controls. The revealed correlation between the concentrations of NETosis markers and anti-β2-GPI antibodies in ovarian cancer suggests a possible pathogenetic role of APA in the progression of ovarian cancer and NETs-mediated prothrombotic state against the background of APA circulation. It can be assumed that APA formed in cancer patients may be one of the triggers of NETosis. NETosis itself contributes to the development of thrombotic events and stimulates further synthesis of APA. Perhaps it is the activation of NETosis that explains the worse prognosis in cancer patients with APA circulation. Conclusion. The results of this study improve the understanding of interactions between the immune and hemostatic systems. Further research is needed to determine the role of APA in NETosis, as well as the role of NETosis and APA circulation in tumor progression, metastasis, and cancer-associated thrombosis. Key words: neutrophil extracellular traps, NETosis, antiphospholipid antibodies, cancer, neutrophils, anti-β2-GPI

Serum miR-181a and miR-25 in patients with malignant and benign breast diseases.

Breast tumor diseases include a wide range of pathologies that require different approaches to their treatment. MicroRNA (miR) levels, reflecting regulation of the gene expression involved in tumorigenesis, can be diagnostic and prognostic markers of breast diseases. The levels of circulating miR-181a and miR-25 were measured in patients with benign breast diseases (BBD), patients with invasive carcinoma of a nonspecific type (ICNT) and also in conditionally healthy women. Expression of both miRs was higher in patients of both groups as compared to controls; at the same time, the content of serum miR-181a and miR-25 was higher in BBD patients than in ICNT patients. The detected changes may be of interest in the context of precancerous changes in BBD. It seems possible to use them in the future as markers of the pathological process as a part of a large diagnostic panel.

Recurrent Metaplastic Breast Cancer with Subtype Converted from Triple-Negative to HER2-Positive: A Case Report and Literature Review

Metaplastic breast cancer (MBC) is an extremely rare malignant breast disease that has rarely been reported. The molecular subtype of MBC is mostly triple-negative, with a high recurrence rate and a worse prognosis. Due to its low HR- and HER2-positive rate, reports on endocrine and targeted therapy are very limited. We report a case of infrequent triple-negative MBC, which, although at an early stage, quickly developed multiple recurrent lesions in the chest wall. The tumor relapsed repeatedly after comprehensive treatment, including surgery, chemotherapy and radiotherapy. However, pathological results after the third surgery suggested that the molecular subtype had changed from triple-negative to HER2-positive. The previous comprehensive treatment had not been able to effectively control the disease, but the patient achieved a long progression-free survival time through chemotherapy and trastuzumab targeted therapy after the subtype change. To date, there has been no recurrence for over eight years. Among repeatedly relapsed MBC patients, further investigation should be taken into consideration. As in the case presented in our study, it is possible that the HER2 status can convert from negative to overexpression. Moreover, for HER2-positive MBC patients, anti-HER2 therapy is recommended. The decision-making process requires multidisciplinary involvement.

Forms of Breast Disorders within Females Visiting Breast Disease Clinic

1.1. Background: Breast disorders, either benign or malignant in nature, are clinically common. The forms of breast disorders vary within different nations. 1.2. Objectives: The goal of the current research study is to explore and observe the forms of breast disease and their correlation with various obtained variables of interest in females visiting the breast disease clinic. 1.3. Methodology: A cross-sectional research study performed at El Sahel Teaching Hospital from 1st of May 2017 till 1st of February 2017. A randomly selected cohort of 500 research subjects of all age categories have been enrolled in the research study. The cases have been cat- egorized according to their clinical diagnosis into 3 classes of breast conditions: normal, benign and malignant. The statistical significance was &lt;0.05. 1.4. Results: breast disorders of benign nature diagnosed among (63%) of cases while breast dis- eases of malignant nature composed of (13.2%). The commonest clinical presentation have been mastalgia and breast mass (39.2%), mastalgia (37.6%), and breast mass only (23.2%). Fibro- adenoma (26.2%) has been the most common benign clinical disease with greatest incidence (76.9%) in the age research group below 20 years. Malignant breast diseases have been more frequent with increasing age. Benign breast clinical disorders and pathological lesions were correlated more with nulliparous females (p&lt;0.001). Breast cancer observed (p &lt;0.001) more frequent in a statistically significant fashion with in lactating females recruited in the research cohort. 1.5. Conclusion: Benign diseases and various disorder of the breast is a popular clinical di- agnosis mostly presented in younger females. Breast malignant disease despite the fact that is clinically diagnosed in lower frequency and mainly presented in older age groups, yet its sig- nificance oblige a meticulous evaluation of females of various clinical presentations particularly that of breast mass only or associated with mastalgia.

A Non-Invasive Deep Photoablation Technique to Inhibit DCIS Progression and Induce Antitumor Immunity

Ductal carcinoma in situ (DCIS) of the breast is often managed by lumpectomy and radiation or mastectomy, despite its indolent features. Effective non-invasive treatment strategies could reduce the morbidity of DCIS treatment. We have exploited the high heat shock protein 90 (HSP90) activity in premalignant and malignant breast disease to non-invasively detect and selectively ablate tumors using photodynamic therapy (PDT). PDT with the HSP90-targeting photosensitizer, HS201, can not only ablate invasive breast cancers (BCs) while sparing non-tumor tissue, but also induce antitumor immunity. We hypothesized that HS201-PDT would both non-invasively ablate DCIS and prevent progression to invasive BC. We tested in vitro selective uptake and photosensitivity of HS201 in DCIS cell lines compared to the non-selective parental verteporfin, and assessed in vivo antitumor efficacy in mammary fat pad and intraductal implantation models. Selective uptake of HS201 enabled treatment of intraductal lesions while minimizing toxicity to non-tumor tissue. The in vivo activity of HS201-PDT was also tested in female MMTV-neu mice prior to the development of spontaneous invasive BC. Mice aged 5 months were administered HS201, and their mammary glands were exposed to laser light. HS201-PDT delayed the emergence of invasive BC, significantly prolonged disease-free survival (DFS) (p = 0.0328) and tended to improve overall survival compared to the no-treatment control (p = 0.0872). Systemic administration of anti-PD-L1 was combined with HS201-PDT and was tested in a more aggressive spontaneous tumor model, HER2delta16 transgenic mice. A single PDT dose combined with anti-PD-L1 improved DFS compared to the no-treatment control, which was significantly improved with repetitive HS201-PDT given with anti-PD-L1 (p = 0.0319). In conclusion, a non-invasive, skin- and tissue-sparing PDT strategy in combination with anti-PD-L1 antibodies effectively prevented malignant progression of DCIS to invasive BC. This non-invasive treatment strategy of DCIS may be safe and effective, while providing an option to reduce the morbidity of current conventional treatment for patients with DCIS. Clinical testing of HS201 is currently underway.