HPV Detection in Breast Tumors and Associated Risk Factors in Northeastern Brazil.

Breast cancer risk factors include lifestyle, genetic-hormonal influences, and viral infections. Human papillomavirus (HPV), known primarily as the etiological agent of cervical cancer, also appears active in breast carcinogenesis, as evidenced in our study of 56 patients from northeastern Brazil. We assessed the clinical and sociodemographic characteristics, correlating them with various breast cancer tumor types. HPV detection involved amplifying the L1 region, with viral load measured using the E2/E6 ratio and viral activity indicated by E5 oncogene expression. Predominantly, patients over 56 years of age with healthy lifestyles showed a high incidence of invasive ductal carcinoma and triple-negative breast cancer. HPV was detected in 35.7% of cases, mostly HPV16, which is associated with high viral loads (80 copies per cell) and significant E5 expression. These results hint at a possible link between HPV and breast carcinogenesis, necessitating further studies to explore this association and the underlying viral mechanisms.

Transcription factor SOX3 upregulated pro-apoptotic genes expression in human breast cancer.

BACKGROUND: Sex-determining region Y-box 3 (SOX3) protein, a SOX transcriptions factors group, has been identified as a key regulator in several diseases, including cancer. Downregulation of transcriptions factors in invasive ductal carcinoma (IDC) can interfere in neoplasia development, increasing its aggressiveness. We investigated SOX3 protein expression and its correlation with apoptosis in the MDA-MB-231 cell line, as SOX3 and Pro-Caspase-3 immunoexpression in paraffin-embedded invasive ductal carcinoma tissue samples from patients (n = 27). Breast cancer cell line MDA-MD-231 transfected with pEF1-SOX3 + and pEF1-Empty vector followed by cytotoxicity assay (MTT), Annexin-V FITC PI for apoptosis percentage assessment by flow cytometry, qPCR for apoptotic-related gene expression, immunofluorescence, and immunohistochemistry to SOX3 immunolocalization in culture cells, and paraffin-embedded invasive ductal carcinoma tissue samples. RESULTS: Apoptotic rate was higher in cells transfected with pEF1-SOX3 + (56%) than controls (10%). MDA-MB-231 transfected with pEF1-SOX3 + presented upregulation of pro-apoptotic mRNA from CASP3, CASP8, CASP9, and BAX genes, contrasting with downregulation antiapoptotic mRNA from BCL2, compared to non-transfected cells and cells transfected with pEF1-empty vector (p < 0.005). SOX3 protein nuclear expression was detected in 14% (4/27 cases) of ductal carcinoma cases, and pro-Caspase-3 expression was positive in 50% of the cases. CONCLUSION: Data suggest that SOX3 transcription factor upregulates apoptosis in breast cancer cell line MDA-MB-231, and has a down nuclear expression in ductal carcinoma cases, and need to be investigated as a tumor suppressor protein, and its loss of expression and non-nuclear action turn the cells resistant to apoptosis. Further studies are necessary to understand how SOX3 protein regulates the promoter regions of genes involved in apoptosis.

The Use of Convolutional Neural Networks in the Prediction of Invasive Ductal Carcinoma in Histological Images of Breast Cancer.

This paper presents a deep learning approach for automatic detection and visual analysis of Invasive Ductal Carcinoma (IDC) tissue regions. The method proposed in this work is a convolutional neural network (CNN) for visual semantic analysis of tumor regions for diagnostic support. Detection of IDC is a time-consuming and challenging task, mainly because a pathologist needs to examine large tissue regions to identify areas of malignancy. Deep Learning approaches are particularly suitable for dealing with this type of problem, especially when many samples are available for training, ensuring high quality of the learned features by the classifier and, consequently, its generalization capacity. A 3-hidden-layer CNN with data balancing reached both accuracy and F1-Score of 0.85 and outperforming other approaches from the literature. Thus, the proposed method in this article can serve as a support tool for the identification of invasive breast cancer.

Invasive ductal carcinoma of the breast in a pregnant woman: case report

Gestational breast cancer is the most common cause of cancer in pregnant women. It is a challenging condition for the medical team, since the physiological changes in the breast during this period increase the density of the breast parenchyma, which makes it difficult to detect the nodule on physical and imaging examination, causing delay in diagnosis. We present here a case report of a woman with breast cancer diagnosed during pregnancy. This was a 28-year-old female patient who arrived at the service at 14 weeks' gestation, diagnosed with invasive ductal carcinoma in the left breast, with T4dN2M0 staging. Neoadjuvant chemotherapy treatment was started with a pause for the cesarean section at 36 weeks' gestation. After delivery, chemotherapy was restarted, followed by radical mastectomy, radiotherapy and hormone therapy. Two years after the initial diagnosis and still being treated with hormone therapy, the patient presented with musculoskeletal pain, detected on magnetic resonance imaging and bone scintigraphy, as well as several points of metastasis in the spine with pathological fracture of L2-L3, where she was then submitted to decompressive laminectomy. After surgery, radiotherapy of the thoracic and lumbar spine was started, in addition to chemotherapy. Currently, the patient is asymptomatic, being on paclitaxel and transtuzumab, with stable bone scintigraphy and radiography and ultrasound showing no metastases, and the child is healthy after three years of follow-up.

MRI-based machine learning radiomics can predict HER2 expression level and pathologic response after neoadjuvant therapy in HER2 overexpressing breast cancer.

BACKGROUND: To use clinical and MRI radiomic features coupled with machine learning to assess HER2 expression level and predict pathologic response (pCR) in HER2 overexpressing breast cancer patients receiving neoadjuvant chemotherapy (NAC). METHODS: This retrospective study included 311 patients. pCR was defined as no residual invasive carcinoma in the breast or axillary lymph nodes (ypT0/isN0). Radiomics/statistical analysis was performed using MATLAB and CERR software. After ROC and correlation analysis, selected radiomics parameters were advanced to machine learning modelling alongside clinical MRI-based parameters (lesion type, multifocality, size, nodal status). For predicting pCR, the data was split into a training and test set (80:20). FINDINGS: The overall pCR rate was 60.5% (188/311). The final model to predict HER2 heterogeneity utilised three MRI parameters (two clinical, one radiomic) for a sensitivity of 99.3% (277/279), specificity of 81.3% (26/32), and diagnostic accuracy of 97.4% (303/311). The final model to predict pCR included six MRI parameters (two clinical, four radiomic) for a sensitivity of 86.5% (32/37), specificity of 80.0% (20/25), and diagnostic accuracy of 83.9% (52/62) (test set); these results were independent of age and ER status, and outperformed the best model developed using clinical parameters only (p=0.029, comparison of proportion Chi-squared test). INTERPRETATION: The machine learning models, including both clinical and radiomics MRI features, can be used to assess HER2 expression level and can predict pCR after NAC in HER2 overexpressing breast cancer patients. FUNDING: NIH/NCI (P30CA008748), Susan G. Komen Foundation, Breast Cancer Research Foundation, Spanish Foundation Alfonso Martin Escudero, European School of Radiology.

Distinct pattern of one-carbon metabolism, a nutrient-sensitive pathway, in invasive breast cancer: A metabolomic study.

Altered cell metabolism is a hallmark of cancer and critical for its development. Particularly, activation of one-carbon metabolism in tumor cells can sustain oncogenesis while contributing to epigenetic changes and metabolic adaptation during tumor progression. We assessed whether increased one-carbon metabolism activity is a metabolic feature of invasive ductal carcinoma (IDC). Differences in the metabolic profile between biopsies from IDC (n = 47) and its adjacent tissue (n = 43) and between biopsies from different breast cancer subtypes were assessed by gas spectrometry in targeted (Biocrates Life Science ® ) and untargeted approaches, respectively. The metabolomics data were statistically treated using MetaboAnalyst 4.0, SIMCA P+ (version 12.01), Statistica 10 software and t test with p < 0.05. The Cancer Genome Atlas breast cancer dataset was also assessed to validate the metabolomic profile of IDC. Our targeted metabolomics analysis showed distinct metabolomics profiles between IDC and adjacent tissue, where IDC displayed a comparative enrichment of metabolites involved in one-carbon metabolism (serine, glycine, threonine, and methionine) and a predicted increase in the activity of pathways that receive and donate carbon units (i.e., folate, methionine, and homocysteine). In addition, the targeted and untargeted metabolomics analyses showed similar metabolomics profiles between breast cancer subtypes. The gene set enrichment analysis identified different transcription-related functions between IDC and non-tumor tissues that involved one-carbon metabolism. Our data suggest that one-carbon metabolism may be a central pathway in IDC and even in general breast tumors, representing a potential target for its treatment and prevention.

N-Acetylglucosaminyltransferase III (GnT-III) but not N-Acetylgalactosaminyltransferase-6 and 8 are Differentially Expressed in Invasive and In Situ Ductal Carcinoma of the Breast.

Mammary carcinoma is the most common malignant tumor in women, and it is the leading cause of mortality. In tumor context, glycosylation promotes post translational modifications necessary for cell progression, emerging as a relevant tumor hallmarker. This study aimed to analyze the association between polypeptide N-acetylgalactosaminyltransferase-6 (ppGalNAc-T6), -T8, N-acetylglucosaminyltransferase III (GnT-III) expression, Phaseolus vulgaris-leucoagglutinin (PHA-L), wheat germ agglutinin (WGA) and peanut agglutinin (PNA) staining with clinic-histopathological factors from patients with pure ductal carcinoma in situ (DCIS) and DCIS with invasive ductal carcinoma (DCIS-IDC) of breast. Formalin-fixed and paraffin-embedded samples (n = 109) were analyzed. In pure DCIS samples GnT-III was over-expressed in comedo lesions (p = 0.007). In DCIS-IDC, GnT-III expression was associated with high nuclear grade tumors (p = 0.039) while the presence of PHA-L and WGA were inversely related to HER-2 expression (p = 0.001; p = 0.036, respectively). These findings pointed to possible involvement of GnT-III, ppGalNAc-T8, L-PHA and WGA as probes in prognostic evaluation of DCIS.

Distorsión de la arquitectura mamaria: la mejor forma de enfrentarla / Distorsion of breast architecture: the best way to confront it

Abstract: Objective. Assess the performance of digital 2D mammography and tomosynthesis in the characterisation of architectural breast distortion (ABD). Material and method. A retrospective study, approved by the Ethics Committee, was conducted on mammographic studies on cases with a diagnosis of ABD selected from August 2015-August 2016. Cases with imaging modalities available on PACS were included: digital mammography (2D), tomosynthesis (TS), ultrasound (US), magnetic resonance (MR), and with biopsy performed at our institution. ABD cases associated with micro-calcifications and post-surgical changes were excluded. Detection rates and imaging characteristics were analysed, as well as the histopathological concordance. Results. A total of 81 cases of ABD without microcalcifications were detected on the mammographs, but only 52 met the inclusion criteria. According to histopathology, 23 (44%) were malignant, 17 (33%) were benign, and 12 (23%) were high-risk lesions. All were detected by TS and US, and classified as suspicious lesions (BI-RADS 4 or 5). In 2D mammography, 24 cases (46%) were not seen and 8 (33%) of these were malignant. Malignant lesions showed dense centres in 87% of cases. The most frequent lesion on ultrasound was a hypoechogenic area (60%) in 86% of lesions with penetrating vessels. A total of 21 MRI were performed, with mass enhancement being identified in all of them. Conclusion. ABD is better displayed in TS than 2D mammography. Despite its characteristics, histological examination is essential (even when a radiolucent centre is observed). Focused US should be the next procedure to follow, since it allows to visualize the lesion to be visualised, and can direct the percutaneous biopsy in most cases.

Resumen: Objetivo. Determinar en qué método de imagen se logra visualizar y caracterizar mejor una distorsión de la arquitectura mamaria (DAM). Material y método. Estudio retrospectivo, aprobado por el Comité de Ética. Se seleccionaron los estudios mamográficos con diagnóstico de DAM en nuestro servicio entre agosto de 2015 y agosto de 2016. Se incluyeron casos estudiados con al menos 3 de las modalidades de imágenes disponibles en PACS: mamografía digital (2D), tomosíntesis (TS), ecografía (US), resonancia (RM) y que fueron biopsiados en nuestra institución. Se excluyeron casos de DAM asociadas con microcalcificaciones y cambios posquirúrgicos. Se evaluaron la tasa de detección, las características imagenológicas y la concordancia histopatológica. Resultados. En 15 meses se detectaron 81 casos de DAM en mamografía; de estos, 52 cumplieron con los criterios de inclusión. Según la histopatología, 23 (44%) resultaron malignas, 17 (33%) benignas y 12 (23%) lesiones de alto riesgo (LAR). Todas fueron detectadas por TS y US, clasificadas como lesiones sospechosas (BI-RADS 4 o 5). En mamografía 2D, 24 casos (46%) quedaron ocultos, y de estos, 8 (33%) resultaron malignos. Las lesiones malignas presentaron centro denso en el 87% de los casos. La lesión más frecuente en ecografía fue el área hipoecogénica (60%), en el 86% de las lesiones con vasos penetrantes. Se contó con 21 RM, identificándose captación tipo masa en las patologías malignas. Conclusión. La DAM es mejor visualizada en TS que en mamografía 2D. Pese a sus características, un estudio histológico es indispensable (incluso al observar un centro radiolúcido). El US dirigido es el paso a seguir, ya que permite visualizar la lesión y dirigir su biopsia percutánea en la mayoría de los casos.

Expresión de los receptores hormonales (RE/RP) y sobreexpresión de la proteína HER-2/neu en carcinoma ductal infiltrante / Expression of hormone receptors receptors (ER/RP) and overexpression of HER-2/neu protein overexpression in infiltrating ductal carcinoma

Introducción: El grado de diferenciación tumoral, la expresión de los receptores de estrógeno y progesterona y la sobreexpresión de la proteína HER-2/neu son factores de tipo pronóstico y predictivo importantes en la evolución y conducta terapéutica del carcinoma mamario infiltrante. Se ha encontrado en diversos estudios que los inmunofenotipos que no expresan los receptores hormonales o que sobre expresan la proteína HER-2/neu se asocian con pobre diferenciación tumoral. Objetivo: Determinar el perfil inmunofenotípico del carcinoma ductal infiltrante y establecer su relación con el grado de diferenciación tumoral. Metodología: Usando técnicas de inmunohistoquímica se determinaron los receptores de estrógeno (RE) y progesterona (RP), y la sobreexpresión de la proteína HER-2/neu en muestras de carcinoma ductal infiltrante y se identificaron sus fenotipos basados en la clasificación de Cheang. La variedad histológica y el grado de diferenciación tumoral en los carcinomas ductales infiltrantes fueron evaluados en tejido coloreado con hematoxilina-eosina. Resultados: Se incluyeron las muestras de 58 pacientes con carcinoma ductal infiltrante. El 15,5% de los carcinomas eran bien diferenciados, 63,8% moderadamente diferenciados y el 20,7% restante pobremente diferenciados. El inmunofenotipo triple negativo se presentó en 29,3% de las muestras, HER2+ en el 20,7%, luminal/ HER2+ en el 1,7%, luminal A en el 43,1% y ER-/PR+/HER2- en el 5,2%. Conclusión: En nuestro estudio, no se encontró asociación entre el grado de diferenciación tumoral y los inmunofenotipos. Salud UIS 2011; 43 (2): 149-158.

Introduction: The degree of tumor differentiation, the expression of estrogen and progesterone receptors and HER-2/ neu protein overexpressing are important prognostic and predictive factors in the evolution and therapeutic management of invasive breast carcinoma. In different studies were found that the immunophenotypes that do not express hormonal receptors or the HER-2/neu protein overexpressing have been associated with poor tumor differentiation. Purpose: To determine the immunophenotypic profile of invasive ductal carcinoma and establish its relationship with the histological grade. Methodology: Using immunohistochemistry were determined the estrogen receptor (ER) and progesterone (PR) and HER-2/neu protein overexpression in invasive ductal carcinoma samples and their phenotypes were identified based on classification of Cheang. The histological subtype and degree of tumor differentiation in invasive ductal carcinomas were evaluated in tissue stained with hematoxylin-eosin. Results: In this study were included 58 patients with invasive ductal carcinoma. 15.5% of the carcinomas were well differentiated, 63.8% moderately differentiated and the remaining 20.7% poorly differentiated. The triple-negative immunophenotype was show in 29.3% of the samples, HER2+ in the 20.7%, luminal/HER2 + in the 1.7%, luminal A in the 43.1% and the phenotype (ER-/PR+/HER2) in the 5.2%. Conclusion: In this study don't was found association between the degree of tumor differentiation and the immunophenotypes. Salud UIS 2011; 43 (2): 149-158.

Expression of e-cadherin, n-cadherin and snail and their correlation with clinicopathological variants: an immunohistochemical study of 132 invasive ductal breast carcinomas in Egypt

OBJECTIVE: To evaluate the expression of the cell adhesion molecules E-cadherin and N-cadherin and the transcription factor Snail in invasive ductal breast carcinomas and to determine their relationships with clinicopathological features. METHODS: Immunohistochemistry was used to examine E-cadherin, N-cadherin, and Snail protein expression in 132 invasive breast carcinomas. RESULTS: The expression of E-cadherin was decreased (negative or weak) in 37.1 percent of invasive carcinomas, while N-cadherin and Snail overexpression were detected in 51.9 percent and 40.9 percent of carcinomas, respectively. Low E-cadherin expression was significantly correlated with poorly differentiated carcinoma (53.1 percent), positive node status (80.9 percent), poor Nottingham Prognostic Index (64.7 percent), and the presence of estrogen and progesterone receptors. Overexpression of N-cadherin and Snail were also significantly correlated with poorly differentiated carcinoma, positive node status, and poor Nottingham Prognostic Index but were correlated with the absence of hormone receptors. Loss of E-cadherin immunoexpression was strongly associated with the presence of membranous N-cadherin (87.8 percent) and nuclear Snail (69.4 percent). CONCLUSION: Loss of E-cadherin and overexpression of N-cadherin and Snail in breast carcinomas may play a central role in the development of invasive ductal breast carcinoma. These biomarkers may provide a valuable reference for the study of invasive ductal carcinoma progression and to characterize the biological behavior of the tumor. In the future, increased N-cadherin and decreased E-cadherin expression may be used as indicators of the progression and prognosis of invasive ductal carcinoma.

Estimating genomic instability mediated by Alu retroelements in breast cancer.

Alu-PCR is a relatively simple technique that can be used to investigate genomic instability in cancer. This technique allows identification of the loss, gain or amplification of gene sequences based on the analysis of segments between two Alu elements coupled with quantitative and qualitative analyses of the profiles obtained from tumor samples, surgical margins and blood. In this work, we used Alu-PCR to identify gene alterations in ten patients with invasive ductal breast cancer. Several deletions and insertions were identified, indicating genomic instability in the tumor and adjacent normal tissue. Although not associated with specific genes, the alterations, which involved chromosomal bands 1p36.23, 1q41, 11q14.3, 13q14.2, occurred in areas of well-known genomic instability in breast and other types of cancer. These results indicate the potential usefulness of Alu-PCR in identifying altered gene sequences in breast cancer. However, caution is required in its application since the Alu primer can produce non-specific amplification.

Estimating genomic instability mediated by Alu retroelements in breast cancer

Alu-PCR is a relatively simple technique that can be used to investigate genomic instability in cancer. This technique allows identification of the loss, gain or amplification of gene sequences based on the analysis of segments between two Alu elements coupled with quantitative and qualitative analyses of the profiles obtained from tumor samples, surgical margins and blood. In this work, we used Alu-PCR to identify gene alterations in ten patients with invasive ductal breast cancer. Several deletions and insertions were identified, indicating genomic instability in the tumor and adjacent normal tissue. Although not associated with specific genes, the alterations, which involved chromosomal bands 1p36.23, 1q41, 11q14.3, 13q14.2, occurred in areas of well-known genomic instability in breast and other types of cancer. These results indicate the potential usefulness of Alu-PCR in identifying altered gene sequences in breast cancer. However, caution is required in its application since the Alu primer can produce non-specific amplification.