Hallazgos mastográficos benignos que simulan malignidad: un dilema diagnóstico / Benign mammographic findings that simulate malignancy: a diagnostic dilemma

Resumen OBJETIVO: Identificar los principales hallazgos histopatológicos benignos y determinar la tasa de falsos positivos que suelen causar conflicto al categorizar las mastografías en el sistema BI-RADS por su aspecto, que puede simular un proceso maligno. MATERIALES Y MÉTODOS: Estudio de cohorte, retrospectivo, efectuado en pacientes atendidas en la Unidad Médica de Alta Especialidad 4 Luis Castelazo Ayala (2019-2023) con reporte mastográfico alterado o sospecha clínica de malignidad. Para el análisis estadístico se utilizó el programa JASP 2.0 y χ2 para la diferencia de proporciones entre grupos. RESULTADOS: De un grupo de 11,481 pacientes, se reportaron 1643 mastografías alteradas: 444 con reportes falsos positivos, 23 pacientes con sospecha clínica y exclusión de 16 que no cumplieron con los criterios de inclusión establecidos. La muestra poblacional estudiada fue de 451 pacientes. La mayoría permaneció asintomática al momento del estudio (42.1%). El hallazgo histopatológico benigno con mayor prevalencia fue el fibroadenoma y su síntoma más relevante el nódulo palpable. La tasa de falsos positivos fue de 4.3%. CONCLUSIONES: En la actualidad, gracias a la implementación de programas de tamizaje es posible establecer diagnósticos de cáncer de mama en etapas tempranas, aunque con la desventaja que el reporte puede resultar falso positivo y ello dar lugar a incremento de la morbilidad y sobretratamiento. Los estándares internacionales indican que estos no deben sobrepasar el 10%.

Abstract OBJECTIVE: To identify the main benign histopathological findings that often cause conflict when categorizing mastographies in the BI-RADS system due to their appearance, which may simulate a malignant process and false positive rate. MATERIALS AND METHODS: Retrospective cohort study carried out in patients attended at the Unidad Médica de Alta Especialidad 4 Luis Castelazo Ayala (2019-2023) with an altered mastographic report or clinical suspicion of malignancy. For statistical analysis we used the JASP 2.0 programme and χ2 for the difference in proportions between groups. RESULTS: From a group of 11,481 patients, 1,643 altered mastograms were reported: 444 with false positive reports, 23 patients with clinical suspicion and exclusion of 16 who did not meet the established inclusion criteria. The population sample studied was 451 patients. The majority remained asymptomatic at the time of the study (42.1%). The most prevalent benign histopathological finding was fibroadenoma and the most relevant symptom was a palpable nodule. The false positive rate was 4.3%. CONCLUSIONS: Currently, thanks to the implementation of screening programmes it is possible to establish breast cancer diagnoses in early stages, although with the disadvantage that the report may be false positive and this may lead to increased morbidity and overtreatment. International standards indicate that these should not exceed 10%.

MRI radiomics for the preoperative evaluation of lymphovascular invasion in breast cancer: A meta-analysis.

PURPOSE: To evaluate the ability of preoperative MRI-based radiomic features in predicting lymphovascular invasion (LVI) in patients with breast cancer. METHODS: PubMed, Embase, Web of Science, Cochrane Library databases, and four Chinese databases were searched to identify relevant studies published up until June 15, 2023. Two reviewers screened all papers independently for eligibility. We included diagnostic accuracy studies that used radiomics-MRI for LVI in patients with breast cancer, using histopathology as the reference standard. Quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 and Radiomics Quality Score. Overall diagnostic odds ratio (DOR), sensitivity, specificity and area under the curve (AUC) were calculated to assess the prediction efficacy of MRI-based radiomic features in patients with breast cancer. Spearman's correlation coefficient was calculated and subgroup analysis performed to investigate causes of heterogeneity. RESULTS: Eight studies comprising 1685 female patients were included. The pooled DOR, sensitivity, specificity, and AUC of radiomics in detecting LVI were 23 [confidence interval (CI) 16,32], 0.89(0.86,0.92), 0.82 (0.78,0.86), and 0.83(0.78,0.87), respectively. The meta-analysis showed significant heterogeneity among the included studies. No threshold effect was detected. Subgroup analysis showed that more than 200 participants, radiomics with clinical factors, semiautomatic segmentation method and peritumoral or intra- and peritumoral model [DOR: 28(18,42), 26(19,37), 34(16,70), 40(10,156), respectively] could improve diagnostic performance compared with less than 200 participants, only radiomics, manual segmentation method, and tumor model [DOR: 16(7,37), 21(6,73), 20(12,32), 21(13,32), respectively], but 3.0 T MR and multiple sequences approach [DOR: 27(15,49),17(8,35)] couldn't improve diagnostic performance compared with 1.5 T and DCE radiomic features [DOR:27(7,99),25(17,37)]. CONCLUSION: Our meta-analysis showed that preoperative MRI-based radiomic features performs well in predicting LVI in patients with breast cancer. This noninvasive and convenient tool may be used to facilitate preoperative identification of LVI in breast cancer.

Redescription of the soft-shell turtle Rafetus bohemicus (Testudines, Trionychidae) from the Early Miocene of Czechia.

The taxonomy of the soft-shell turtle Rafetus bohemicus (Liebus, 1930), family Trionychidae, subfamily Trionychinae, is revised based on new and previously mentioned material (including the type material) from the Early Miocene (Burdigalian, MN 3) sites of the Most Basin, Czechia. Given that the diagnosis was so far based only on plastral elements, here we focused on the cranial material and combined our study with previously published data on postcranial elements. 3D models of the skulls derived from CT scans allow us to provide the first complete skull description of R. bohemicus, including several new cranial diagnostic characters of the species. Our results not only enable the distinction of the trionychid genera Trionyx and Rafetus, both recorded from Central Europe during the Early Miocene, but further allow us to provide an emended diagnosis for R. bohemicus. We confirm the conclusions of a previous study according to which Trionyx pontanus, T. preschenensis, T. aspidiformis, and T. elongatus are nomina dubia. R. bohemicus from Brest'any (MN 3) represents the oldest record of this genus in Europe as well as the oldest occurrence of the genus.

SDC4-rs1981429, ATM-rs228590 and biomarkers of breast cancer risk.

This is a correspondence on published article on SDC4-rs1981429, ATM-rs228590 and biomarkers of breast cancer risk. Confounding factors are discussed.

Cáncer de mama en hombres: revisión de casos en el Hospital Regional de Talca / Breast cancer in men: review of cases at "Hospital Regional de Talca"

Breast cancer in men is a rare pathology. The most common clinical presentation is a palpable and painless retroareolar nodule. In men, it is a rare pathology, there are few studies on the matter, where breast cancer trials frequently exclude men. Objective: to present the incidence of breast cancer in men from the "Regional Hospital of Talca" Method: Retrospective and descriptive study of cases of breast cancer in men who have been treated and followed up in the Breast Pathology Unit of the Regional Hospital of Talca from January 1, 2011 to December 31, 2021.Results: There were 9 cases of breast cancer in men. Average age at diagnosis was 63 years, all patients were 50 years of age or older. One hundred percent of patients consulted for a self-palpable breast nodule. Average size on physical examination was 30 mm. The most frequent histology was invasive ductal carcinoma (56%), followed by invasive tubular carcinoma (22%) and ductal carcinoma in situ (11%). Immunohistochemistry was 100% positive for estrogen and progesterone receptor. Surgery in 56% of cases was total mastectomy with axillary dissection, and in 33% it was total mastectomy alone. 4 patients underwent adjuvant treatment with chemotherapy, and just one required a combination of chemotherapy and radiotherapy. During follow-up, only 2 patients died. Conclusion. Breast cancer in men is not very prevalent and the management is extrapolated from large studies in women, we believe that it is essential to have studies in male patients, to really have clarity on the behavior and evolution of the disease.

Multiparametric Magnetic Resonance Imaging in Evaluation of Benign and Malignant Breast Masses with Pathological Correlation.

Background Dynamic contrast-enhanced (DCE) MRI sequences plays a vital role in diagnosing breast masses with high sensitivity and specificity as compared to other diagnostic modalities. The addition of diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) values significantly improves diagnostic accuracy. This study aimed to study the breast masses on DCE-MRI, restricted diffusion on DWI, ADC values, and choline peak on spectroscopy in breast cancer diagnosis. Material and methods This study was a prospective observational study which involved subjects with breast lumps. Baseline data was collected from the patients along with pertinent clinical history and relevant laboratory investigations. MR mammography (MRM) was performed on a 1.5 Tesla MR Scanner (MAGNETOM® Avanto, Siemens AG, Munich Germany) using a dedicated double breast coil. Results Forty-one subjects were included with a total of 54 breast masses in them. The mean age of the study population was 47.1±14.7 years. From the MRI final diagnosis, the majority (53.70%) were diagnosed as malignant lesions and 46.30% as benign. Out of 20 lesions diagnosed as benign on histopathology, only five percent had ADC value <1.3 ×10-3mm2/s, and the majority (95%) had ADC value >1.3 ×10-3mm2/s. All 20 lesions were circumscribed, ovoid, or round in shape showing no restricted diffusion on DWI, with corresponding ADC value of >1.3×10-3mm2/s, homogeneous post-contrast enhancement, or with dark internal septations, type I kinetic enhancement curve, and they showed no choline peak on spectroscopy. Out of 34 malignant lesions diagnosed on histopathology, the majority (85.29%) displayed restricted diffusion on DWI and had an ADC value of <1.3×10-3mm2/s, most of them had spiculated margins, type II/ III kinetic curve with choline peak on spectroscopy. Conclusion Multiparametric MR mammography, which included DCE-MRM, DWI, ADC values, and spectroscopy, correlated well with the histopathological diagnosis of benign and malignant breast masses.

Caracterización del cáncer de mama en el hombre. Experiencia del Hospital Británico de Buenos Aires / Characterization of breast cancer in men. Experience of the British Hospital of Buenos Aires

Introducción: El cáncer de mama en el hombre es una patología poco frecuente, que representa el 1% de todos los tumores malignos masculinos y menos del 1% de todos los carcinomas mamarios, cuyas dos características fundamentales son la aparición tardía y la presentación en estadios avanzados. Objetivo: Presentar los 38 casos tratados en el Servicio de Mastología del Hospital Británico de Buenos Aires y comparar los hallazgos con publicaciones anteriores. Material y método: Estudio retrospectivo de pacientes tratados por cáncer de mama en el Servicio desde enero del 1973 a mayo del 2018. Resultados: Edad media 63,9+12.8 años. Tamaño tumoral: 1,9 +0.9 cm. Se realizó Mastectomía radical modificada en 61% de los pacientes. Tipo histológico más frecuente: Ductal Infiltrante en 89,5% de los casos. Hallazgos que concuerdan con publicaciones de otros centros. Discusión: La presentación ocurre en edades avanzadas. La demora en la consulta y la falta de educación sanitaria condicionan las posibilidades de curación. Conclusiones: El cáncer de mama masculino se presenta a avanzada edad, con una importante demora en la consulta y en estadios avanzados. En la actualidad su manejo se extrapola de conductas llevadas a cabo en mujeres.

Introduction: Breast cancer in male patients in an uncommon disease, which represents 1% of all male malignancies and less than 1% of all breast carcinomas, whose two fundamental characteristics are evident: the late appearance and the presentation in advanced stages. Objective: To present the 38 cases treated in the Mastology Service of the British Hospital of Buenos Aires and compare the findings with previous publications. Material and method: Retrospective study of patients treated for breast cancer in the Servic between january 1973 to may 2018. Results: Average age was 63,9 ± 12,8 years. Tumor size: 1.9 ± 0.9 cm. A Modified radical mastectomy was performed in 61% of patients. Most frequent histological type was Infiltrating Ductal Carcinoma in 89,5% of cases. Findings that match publications from other centers. Discussion: Presentation occurs at advanced ages. The delay in consultation and the lack of health education determine the possibilities of healing. Conclusions. Male breast cancer occurs at an advanced age, with a significant delay in the consultation. At present, its management is extrapolated from guidelines carried out in women.

Proliferación vascular atípica mamaria inducida por radioterapia / Atypical vascular proliferation of the breast induced by radiation

La proliferación vasculara típica mamaria inducida por radioterapia es una proliferación angiomatoide que aparece sobre la piel previamente irradiada por el tratamiento conservador de un carcinomademama. Se presenta el caso de una paciente de 58años que consultó por la aparición de múltiples pápulas purpúricas milimétricas en la mama derecha. Había recibido radioterapia y cuadrantectomía por un carcinoma intraductal 5años antes y estaba medicada con tamoxifeno. El análisis histópatológico e inmunohistoquímico informó: "Proliferación vascular atípica inducida por radiación, variedad atípica inducida por radiación, variedad linfática". Se adoptó una conducta expectante, con seguimiento estrecho.

Atypical vascular proliferation of the breast induced by radiation is an angiomatoid proliferation that appears on previously irradiated skin by the conservative treatament of a breast carcinoma. We present a 58-year-old female patient who consulted for multiple millimeter purpuric papules in the right breast. She received radiotherapy and quadrantectomy for an intraductal carcinoma 5 years before. She is currently on tomoxifen. The histopathology and immunohistochemistry reported atypical vascular proliferation induced by radiation, lymphatic variety. Watchuful waiting is adopted with close monitoring.

Privacy Preserving Association Rule Mining on Distributed Healthcare Data: COVID-19 and Breast Cancer Case Study.

Association rule mining can be used in healthcare data mining to provide solutions to life-threatening diseases like recent COVID-19. Due to healthcare data privacy concerns, privacy preserving distributed healthcare data mining becomes the primary focus of medical science research. Recently, Chahar et al. (Sadhana 42:1997-2007, 2017) proposed privacy preserving distributed association rule mining scheme with insecure communication channels. They used the concept of an elliptic curve-based paillier cryptosystem to achieve privacy, authenticity, and integrity. We observed some security vulnerabilities in their privacy preserving association rule mining scheme when implemented with insecure communication channels. We observed that the security vulnerabilities will result in the disclosure of private data of sites (or participants). Furthermore, we propose a secure version of their scheme to solve the security vulnerabilities with insecure communication channels. Theoretical and experimental analysis shows that the proposed scheme has almost equal computation and communication complexities with better securities. A case study on the effectiveness of the proposed approach in combating COVID-19 coronavirus and Breast Cancer is also discussed.

Effects of yoga on health-related quality, physical health and psychological health in women with breast cancer receiving chemotherapy: a systematic review and meta-analysis.

BACKGROUND: Yoga receive more attention from breast cancer patients, however its feasibility and efficacy during chemotherapy remains conflicting. We performed this systematic review to assess the effects of yoga on health-related quality, physical health and psychological health in breast cancer patients undergoing chemotherapy. METHODS: A systematic search was conducted to retrieve randomized controlled trials (RCTs) which investigated the comparative efficacy of yoga versus comparators such as usual care among breast cancer patients for health-related quality, physical health and psychological health in PubMed, EMBASE, Cochrane Central Register of Controlled Trials (CNETRAL), Nursing and Allied Health Literature (CINAHL), Chinese Biomedical Literature (CBM) Database, China Science and Technology Journal (CSTJ) Database, China National Knowledge Infrastructure (CNKI), and Wangfang Database from inception to December 2018. The latest search was updated on September 2020. All analyses were completed using RevMan version 5.3. RESULTS: Seven trials involving 693 breast cancer patients met inclusion criteria. Meta-analysis indicated a short-term improvement in fatigue [standard mean difference (SMD), -0.62; 95% confidence interval (CI), -1.17 to -0.07], sleep disturbance (SMD, -0.34; 95% CI, -0.55 to -0.12), depression (SMD, -0.50; 95% CI, -0.70 to -0.31) anxiety (SMD, -0.50; 95% CI, -0.70 to -0.31), and health-related quality of life (QoL) (SMD, 0.72; 95% CI, -0.12 to 1.56) in the yoga group; however beneficial medium- and long-term effects in fatigue, sleep disturbance were not identified. Moreover, qualitative analyses suggested that yoga was not associated with decreased adverse events (AEs) compared with control groups. CONCLUSIONS: Yoga may benefit to reduce fatigue, depression and anxiety, improve sleep disturbance, and improve QoL in breast cancer patients receiving chemotherapy in the short-term; however, medium- and long-term effects should be further established owing to limitations.

The impact of cognitive impairment on survival and medication adherence among older women with breast cancer.

INTRODUCTION: The purpose of this study was to examine the impact of preexisting cognitive impairments on survival and medication adherence, and whether chronic medication adherence mediates or moderates the association between cognitive impairments and mortality in patients with breast cancer. METHODS: This retrospective cohort study of older female patients diagnosed with breast cancer was conducted using the Surveillance, Epidemiology, and End Results Medicare Linked Database. We examined the risk of mortality from cancer and non-cancer causes in patients with and without a history of cognitive impairment. In addition, we examined if chronic medication adherence rates differ between these groups of patients and if medication adherence mediates or moderates the association between cognitive impairments and non-cancer mortality. RESULTS: Mortality from cancer-specific (HR 1.13, 95% CI 1.04-1.23) and non-cancer causes (HR 1.16, 95% CI 1.11-1.21) as well as all-cause mortality (HR 1.30, 95% CI 1.23-1.38) was significantly higher in patients with cognitive impairments compared to those without cognitive impairment. Both groups showed low adherence levels to chronic medication before and after the breast cancer diagnosis. Further analysis did not show that medication adherence mediates or moderates the relationship between cognitive impairment and non-cancer mortality (p value > 0.05). CONCLUSION: The results of this study indicate that older female patients with cognitive impairments and a breast cancer diagnosis have a heightened risk of cancer-specific and non-cancer mortality. Our findings do not indicate that chronic medication adherence plays a role in the association between a history of cognitive impairment and mortality, it is still necessary to further investigate this issue.

Características clínico patológicas del cáncer de mama asociadas a la expresión del marcador celular Ki-67 en el Hospital Nacional Edgardo Rebagliati Martins, 2013-2017 / Clinical pathological features of breast cancer associated with the expression of the Ki-67 cell marker at Edgardo Rebagliati Martis National Hospital, 2013-2017

Introducción. El cáncer de mama es la tercera causa de muerte en mujeres peruanas, siendo una enfermedad genéticamente heterogénea, no existen estudios sobre el comportamiento del marcador de proliferación celular Ki-67 en esta población. Objetivo. Analizar la asociación entre las características clínico patológicas del cáncer de mama y la expresión del marcador celular Ki-67 en el Hospital Nacional Edgardo Rebagliati Martins (HNERM), Lima-Perú. Métodos. Estudio retrospectivo, realizado con las muestras diagnósticas de 209 pacientes con cáncer de mama. Las características clínico patológicas evaluadas fueron: edad, tipo histológico, tamaño tumoral, grado histológico, invasión linfovascular, ganglio linfático axilar, estadío clínico según el TNMp, receptor estrógenos (RE), receptor de progesterona (RP), y los inmunofenotipos Her2+, triple positivo (TP) y triple negativo (TN). La expresión del marcador celular Ki-67 fue categorizado como bajo (Ki-67<20%) y alto (Ki-67>20%). Resultados. La expresión alta del marcador celular Ki-67 se asoció con tumores de 2 cm, grado histológico 2 y 3, mayor número de ganglios axilares afectados y los inmunofenotipos Her2+ y triple negativo. La expresión baja del Ki-67 (<20%) se asoció con los tumores estrógeno y progesterona positivo. Conclusión. El marcador celular Ki-67 con expresión alta (>20%) mostró asociación significativa con características tumorales de mal pronóstico conocidas en cáncer de mama.

Introduction. Breast cancer is the third cause of death in peruvian women, a genetically heterogeneous disease, there are no studies on the behavior of the Ki-67 cell proliferation marker in this population. Objective. To analyze the association between the clinical pathological characteristics of breast cancer and the expression of the Ki-67 antigen in Hospital Nacional Edgardo Rebagliati Martins (HNERM), Lima-Perú. Methods. A retrospective study conducted in diagnostic samples of 209 patients with breast cancer. The clinical pathological characteristics were: age, histological type, tumor size, histological grade, lymphovascular invasion, axillary lymph node, clinical stage (TNMp), RE, RP, Her2+, triple positive, triple negative. The Ki-67 cell marker expression was categorized as low (Ki-67<20%) and high (Ki-67>20%). Results. High expression of the Ki-67 cell marker (>20%) was associated with tumors of 2cm, histological grade 2 and 3, greater number of axillary ganglia affected and Her2+ and triple negative inmunophenotypes. Low expression of Ki-67 (<20%) was associated with estrogen and progesterone positive tumors. Conclusion. The Ki-67 cell marker with high expression (>20%) shows a significant association with characteristics of poor prognosis well known in breast cancer.

A multiple breast cancer stem cell model to predict recurrence of T1-3, N0 breast cancer.

BACKGROUND: Local or distant relapse is the key event for the overall survival of early-stage breast cancer after initial surgery. A small subset of breast cancer cells, which share similar properties with normal stem cells, has been proven to resist to clinical therapy contributing to recurrence. METHODS: In this study, we aimed to develop a prognostic model to predict recurrence based on the prevalence of breast cancer stem cells (BCSCs) in breast cancer. Immunohistochemistry and dual-immunohistochemistry were performed to quantify the stem cells of the breast cancer patients. The performance of Cox proportional hazard regression model was assessed using the holdout methods, where the dataset was randomly split into two exclusive sets (70% training and 30% testing sets). Additionally, we performed bootstrapping to overcome a possible biased error estimate and obtain confidence intervals (CI). RESULTS: Four groups of BCSCs (ALDH1A3, CD44+/CD24-, integrin alpha 6 (ITGA6), and protein C receptor (PROCR)) were identified as associated with relapse-free survival (RFS). The correlated biomarkers were integrated as a prognostic panel to calculate a relapse risk score (RRS) and to classify the patients into different risk groups (high-risk or low-risk). According to RRS, 67.81 and 32.19% of patients were categorized into low-risk and high-risk groups respectively. The relapse rate at 5 years in the low-risk group (2.67, 95% CI: 0.72-4.63%) by Kaplan-Meier method was significantly lower than that of the high-risk group (19.30, 95% CI: 12.34-26.27%) (p <  0.001). In the multiple Cox model, the RRS was proven to be a powerful classifier independent of age at diagnosis or tumour size (p <  0.001). In addition, we found that high RRS score ER-positive patients do not benefit from hormonal therapy treatment (RFS, p = 0.860). CONCLUSION: The RRS model can be applied to predict the relapse risk in early stage breast cancer. As such, high RRS score ER-positive patients do not benefit from hormonal therapy treatment.

Estrogen stimulates female cancer progression by inducing myeloid-derived suppressive cells: investigations on pregnant and non-pregnant experimental models.

OBJECTIVE: To investigate the clinical implications of 17ß-estradiol (E2) in estrogen receptor α (ERα)-negative female cancer progression as well as the underlying biological mechanisms. METHODS: Clinical data from 306 locally-advanced cervical cancer (stage IIB-IVA) patients were analyzed in order to investigate the relationships between age, serum E2 levels, and treatment outcomes. Clinical samples, ERα-negative cervical and breast cancer cell lines, and mouse xenograft models of cervical and breast cancers were employed in order to elucidate the mechanisms responsible for the E2- and pregnancy-mediated progression of cervical and breast cancers, with a focus on the role of myeloid-derived suppressor cells (MDSC). RESULTS: Younger patients with elevated E2 levels showed significantly shorter progression-free survival (P = 0.040) and overall survival (P = 0.039). The exogenous E2 treatment stimulated the mobilization of MDSC from bone marrow and directly augmented their suppressive activities, leading to the progression of ERα-negative cervical and breast cancers. The co-administration of an anti-Gr-1 neutralizing antibody with E2 prevented the E2-mediated induction of MDSC, and attenuated E2-mediated tumor growth in cervical and breast cancer xenografts. Significantly increased MDSC numbers and enhanced tumor growth were observed during pregnancy in mice with cervical or breast cancer. Significantly increased MDSC numbers were also observed during pregnancy in cervical cancer patients. CONCLUSIONS: E2 facilitates the progression of ERα-negative cervical or breast cancer under non-pregnant and pregnant conditions by inducing MDSC. MDSC inhibition therapy may have therapeutic efficacy in premenopausal or pregnant female cancer patients.

Histogram analysis of quantitative pharmacokinetic parameters on DCE-MRI: correlations with prognostic factors and molecular subtypes in breast cancer.

BACKGROUND: Breast cancer heterogeneity influences poor prognoses thorough therapy resistance. This study quantitatively evaluated intratumoral heterogeneity through a histogram analysis of dynamic contrast-enhanced MRI (DCE-MRI) pharmacokinetic parameters, and determined correlations with prognostic factors and molecular subtypes. METHODS: We retrospectively investigated 101 invasive ductal breast cancers from 99 women who underwent preoperative DCE-MRI between July 2012 and November 2014. Pharmacokinetic parameters (Ktrans, kep, and ve) were obtained by the Tofts model. For each parameter, the mean, standard deviation, coefficient of variation, skewness, and kurtosis values of tumor were calculated, and prognostic factors and subtypes associations were assessed. RESULTS: The mean of ve was lower in cancers with high Ki-67 than in cancers with low Ki-67 (P = 0.002). The coefficient of variation of ve was higher in cancers with estrogen receptor negativity than in cancers with estrogen receptor positivity (P < 0.001). The coefficient of variation of ve was also higher in cancers with high Ki-67 than in cancers with low Ki-67 (P < 0.001). The skewness of ve was higher in cancers with high nuclear grade than in cancers with low nuclear grade (P = 0.006). Triple-negative cancers showed higher ve coefficient of variation than did those with luminal A (P < 0.001) and B (P = 0.006). CONCLUSIONS: Various ve parameters correlated with breast cancer prognostic factors and molecular subtypes.

Receptor tyrosine kinases (RTKs) in breast cancer: signaling, therapeutic implications and challenges.

Breast cancer is a multifactorial disease and driven by aberrant regulation of cell signaling pathways due to the acquisition of genetic and epigenetic changes. An array of growth factors and their receptors is involved in cancer development and metastasis. Receptor Tyrosine Kinases (RTKs) constitute a class of receptors that play important role in cancer progression. RTKs are cell surface receptors with specialized structural and biological features which respond to environmental cues by initiating appropriate signaling cascades in tumor cells. RTKs are known to regulate various downstream signaling pathways such as MAPK, PI3K/Akt and JAK/STAT. These pathways have a pivotal role in the regulation of cancer stemness, angiogenesis and metastasis. These pathways are also imperative for a reciprocal interaction of tumor and stromal cells. Multi-faceted role of RTKs renders them amenable to therapy in breast cancer. However, structural mutations, gene amplification and alternate pathway activation pose challenges to anti-RTK therapy.

Correlation between clinical response to sorafenib in hepatocellular carcinoma treatment and polymorphisms of P-glycoprotein (ABCB1) and of breast cancer resistance protein (ABCG2): monocentric study.

OBJECTIVES: We studied the relation between the polymorphism of P-glycoprotein (P-gp) and of breast cancer resistance protein (BCRP), encoded by ABCB1 and ABCG2 genes, respectively, and the pharmacokinetic variability and clinical response during the treatment with sorafenib of hepatocellular carcinoma. METHODS: At the Paul Brousse Hospital in Villejuif, France, 47 consecutive patients with advanced HCC treated with a single agent sorafenib, were enrolled. Sorafenib exposure was measured by its plasma concentration 3 h after oral administration of 400 mg (bid) by liquid chromatography. All enrolled patients were genotyped for ABCB1 (rs2032582; rs1045642) and ABCG2 (rs2231137; rs2231142; rs2622604) by blood genomic DNA extraction and Mass ARRAY genotyping. The clinical response was evaluated after 3months of treatment according to the RECIST criteria. KEY FINDINGS: Significant associations between sorafenib exposure and the studied polymorphisms were observed for ABCB1 3435C>T, ABCG2 34G>A, ABCG2 1143C>T and ABCG2 421C>A, but not for ABCB1 2677G>TA SNP. In heterozygous patients for ABCB1 3435 C>T, ABCG2 34 G>A and ABCG2 1143 C>T polymorphisms were significantly associated with the lowest sorafenib plasma levels. Those patients presented a tendency to have the best clinical evolution. CONCLUSION: Heterozygous forms of the studied polymorphisms could be associated with a better therapeutic response.

Lack of association between MTHFR C677T polymorphism and breast cancer risk in Ahvaz, west south-Iran.

BACKGROUND: Association between C677T polymorphism of the methylenetetrahydrofolate reductase (MTHFR), a key enzyme involved in folate metabolism and DNA methylation, and breast cancer risk are inconsistent. We investigated in a case-control study, possible effect of the common MTHFR C677T polymorphism on breast cancer risk in a sample of Iranian patients. MATERIALS AND METHODS: The study subjects comprised of 123 breast cancer cases and 110 cancer-free control, who were matched for age and body mass index (BMI). C677T genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. Lipid profile was measured in all subjects by standard method. RESULTS: The genotypes distributions (CC, CT, and TT) were 55.3, 39, and 5.7% in breast cancer cases and 51.8, 44.5, and 3.6% in controls. Chi square analysis revealed that there was no significant association between breast cancer risk and MTHFR genotypes and alleles. Additionally, no significant association was observed between C677T genotypes and biochemistry parameters. A multinomial logistic regression model with MTHFR genotypes, lipid profiles, BMI and age as covariates revealed that there is no significant association between MTHFR genotypes and risk of breast cancer, but higher values of LDL and HDL significantly increase risk of breast cancer. CONCLUSIONS: Our findings do not support the hypothesis that genetic variation in the MTHFR C677T polymorphism is implicated in the breast cancer risk in a sample of Iranian patients.

A study on the social representations and social memory of Brest, a French city destroyed during the Second World War / Um estudo sobre a representação social e memória social de Brest, uma cidade francesa destruída na Segunda Guerra Mundial

We studied the socio-spatial representations and collective memory of Brest, a city that was heavily destroyed during the Second World War, among a sample of young residents. The methodology used combined word associations, open questions in the form of a questionnaire, and cognitive maps. The results show that participants' representations of Brest are situated in the present because the city is the context in which they experience important (personal and professional) life stages. The painful past of the war is remembered superficially, as if the urban monuments ­ the physical symbols of history ­ do not hold much significance for the city's young people. We conclude by formulating several hypotheses on the social representations of this "old and forgotten" Brest by new generations, alongside a discussion on two major issues: the trauma of the war and the city's military function as a naval base. (AU)

As representações sócio espaciais e a memória coletiva de jovens acerca de Brest, uma cidade destruída na Segunda Guerra Mundial, foram estudadas. A metodologia usou tanto associações livres de palavras quanto perguntas abertas inseridas em questionário e mapas cognitivos. Os resultados mostram que as representações dos participantes acerca de Brest se situam no presente pois a cidade é o contexto onde vivenciam importantes etapas de suas vidas (pessoais e profissionais). O doloroso passado bélico é lembrado superficialmente, como se os monumentos urbanos ­ símbolos físicos da história- não significassem muito para os jovens desta cidade. Concluímos com a formulação de algumas hipóteses sobre a representação social de novas gerações sobre esta "antiga e esquecida" Brest, também discutimos duas grandes questões: o trauma da guerra e a função militar da cidade ao acolher a base naval. (AU)