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El presente trabajo identifica las principales características de la comunidad Chachi dentro de la provincia de Esmeraldas. Una vez identificadas sus principales actividades, encauzadas siempre a la conservación de sus costumbres ancestrales, se planteará una matriz de marco lógico como inicio de un proyecto social que se orienta a su inclusión en las actividades económicas modernas, en base a los productos que producen, es decir la tecnificación de sus procesos productivos. Para esto, primero se debe asegurar el que la comunidad tenga acceso a la energía eléctrica, la misma que se distribuirá en el proyecto mediante el método de implementación de energía fotovoltaica. Esta inclusión, sin poner en riesgo la memoria histórica de los pueblos, tiene la filosofía de que los productos que son creados de manera artesanal, puedan ser producidos en una mayor cantidad y de manera más económica para incluirlos en la comercialización de los mercados locales. Finalmente se debe dar a conocer que este será un proyecto en base a un convenio entre CELEC EP Unidad de Negocio Termoesmeraldas y el Gobierno Autónomo descentralizado de la provincia de Esmeraldas (GADPE) y diversos actores que poseen influencia directa sobre el tema presentado en el artículo.

AimTo analyse the expression of adiponectin (ADIPOQ), and its receptors ADIPOR1 and ADIPOR2, in breast cancer tissue of postmenopausal women with different body mass indexes (BMIs).Subjects and methodsOne hundred and fifty postmenopausal Mexican-Mestizo women with breast cancer were included. BMI was determined in each case. To carry out qualitative and semiquantitative assessments of protein expression by immunohistochemistry, the H-Score method was used, through ImageJ's IHC Profiler software. Statistical power of the study was >80% with a pResultsFifty women had a normal BMI, 50 presented overweight and 50 had obesity. The expression of ADIPOQ in breast cancer tissue of postmenopausal woman with normal BMI was higher in comparison to women with overweight or with obesity (p=0.002 and pConclusionsWe found that women with overweight or obesity had a lower expression of ADIPOQ and a higher ADIPOR1 expression in breast cancer tissue, when compared with women with a normal BMI.

Objective The aim of this study was to compare the population structure of three different representative groups of E. coli isolates causing urinary tract infections in a large area of Madrid, Spain: two groups of multidrug resistant isolates (MDR), ESBL- and non-ESBL producers, and one of fully-susceptible isolates (35 isolates in each group). Methods Epidemiological relatedness was studied by pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). The presence of genes encoding ESBL was determined by using PCR and sequencing. Antimicrobial susceptibility testing was performed by broth microdilution. Results PFGE analysis revealed a high degree of genetic diversity in susceptible and non-ESBL-MDR groups. However, the ESBL-MDR E. coli population was less diverse and a large cluster consisting of ST131 and CTX-M-15-producing isolates was detected. Conclusions The present study revealed that ESBL-producing-MDR E. coli population was less diverse than the non-ESBL MDR group and that ST131 was dominant among CTX-M-15-producing isolates that reflects the spread of this successful MDR lineage.

e18669 Background: Adherence to BCCPG improves outcomes for patients with breast cancer. However, the implementation of international BCCPG may not be feasible in low- and middle-income countries, and a potential solution may be developing BCCPG adapted to local contexts. The National Consensus on Diagnosis and Treatment of Breast Cancer ( Colima Consensus, http://consensocancermamario.com) is the Mexican BCCPG. This study aimed at evaluating physicians’ uptake of the Colima Consensus and identifying barriers impacting adherence. Methods: A cross-sectional, 30-item survey exploring adherence, barriers, and attitudes towards the Colima Consensus was e-mailed to Consensus attendees and members of the Mexican Society of Oncology and Mexican Mastology Association. Answers were collected between 06/21-09/21. Descriptive statistics, univariate, and multivariate analysis were used to analyze the associations between participants’ characteristics, adherence, attitudes, and barriers. Results: Among 1553 physicians invited to participate, 439 (28%) completed the survey. Fifty-four percent were male, 66% were age 30-49 years, and 39% practiced in Mexico City. Twenty-six percent were surgical, 13% medical, and 10% radiation oncologists. Ninety-two percent reported using the Consensus to guide decision-making, 78% adhered to its recommendations, 89% agreed with its recommendations, and 94% believed it was applicable to their clinical practice. Regarding attitudes towards the Consensus, 90% agreed/strongly agreed with it being a good educational tool, 89% a reliable source of information, and 90% thought it improved quality of care. The most common barriers to adherence were lack of resources (54%) and logistical problems (29%). Physicians working with a multidisciplinary team were less likely to cite lack of resources as reason for non-adherence (p < 0.01). Forty percent reported using the Consensus as their only BCCPG. Surgical oncologists (p < 0.01), those practicing in public hospitals (p < 0.01), in institutions with local BCCPG (p < 0.01), with ≤5 new patients/month (p < 0.01), and not involved in research (p < 0.01) were more likely to use the Consensus as their only BCCPG. In multivariate analysis, being a surgical oncologist (OR 3.26, p < 0.01) and working in a public hospital (OR 2.12, p < 0.01) increased the odds of using the Consensus as the only BCCPG. Conclusions: We show high levels of adherence and positive attitudes towards the Colima Consensus, with a significant proportion using it as their main BCCPG. Lack of resources and logistical issues were the main barriers to adherence. Our results highlight the relevance of local BCCPG and suggest a need for the creation of stratified recommendations adapted to various healthcare settings.

AimTo analyse the fibronectin type III domain containing 5 (FNDC5)/irisin expression in tumour tissue of postmenopausal women presenting breast cancer and different body mass indexes (BMIs), proposing that obesity deregulates the expression of FNDC5/irisin at the breast tumour level. In addition, we investigated if different breast cancer cell lines are capable to synthesise this protein.MethodsA total of 150 postmenopausal women (50 with a normal BMI, 50 presenting overweight and 50 having obesity) diagnosed with operable breast cancer were included. FNDC5/irisin expression was determined by immunohistochemistry or by immunocytochemistry. Qualitative analysis of protein expression was performed by the H-Score method, through ImageJ’s IHC Profiler software. Statistical analyses were carried out using STATA V.14.0 (Texas, USA); p value80% with a pResultsFNDC5/irisin expression in breast cancer tissue of postmenopausal women with obesity was significantly increased when compared with FNDC5/irisin expression in women with a normal BMI (p=0.001). Furthermore, three breast cancer cell lines studied were capable to synthesise and express FNDC5/irisin, being the BT-474 cell line the one that exhibited the highest intensity of expression.ConclusionsOur results confirm that women with breast cancer and obesity exhibit an increased irisin expression in their tumorous tissue compared with women with breast cancer and normal BMI. Likewise, in vitro breast cancer cell lines have the capacity to synthesise and express FNDC5/irisin, without any extracellular stimuli, however the microenvironment surrounding these cells in vivo participates in its regulation.

Objetivo: demostrar que la agricultura es el inicio de un proceso autogenerador ligado a la producción y consumo de alimentos que permitan mejorar el estado nutricional y de salud promoviendo la seguridad alimentaria en dos comunidades rurales de Quintana Roo, México. Metodología: estudio cualitativo de corte trasversal y analítico que se realizó en San Pedro Peralta y Lázaro Cárdenas del Río II, Othón P. Blanco, Chetumal, Quintana Roo, con un muestreo no probabilístico realizando trabajo de campo y aplicación de encuestas alimentarias para conocer los productos consumidos y sus frecuencias para determinar el estado de nutrición, seguridad alimentaria y la salud de los participantes. Resultados: casi el 60 % de los encuestados tienen una buena alimentación que consiguen mayormente en tiendas de su propia comunidad y un 20 % proviene de su propia producción. Limitaciones: el presente estudio no alcanzó a cubrir la totalidad de hogares, por falta de tiempo en la visita a las comunidades, sin embargo, es una muestra representativa que nos arroja una perspectiva de la situación alimentaria en estos dos municipios. Conclusiones: existe un nivel de seguridad alimenticia dado que existe una relación entre lo que se produce y consume localmente que atienden a la nutrición y sus enfermedades. Esto verifica que existe un sistema auto sostenido que inicia con la agricultura y que garantiza la seguridad alimentaria. Hay posibilidades de mejorar o aumentar la seguridad alimentaria a través de la información sobre la importancia de la agricultura, la nutrición y la salud.

Objectives: The aim of this this study was to describe the presence of different variants of the fosA gene in fosfomycin-resistant Escherichia coli strains in Madrid, Spain. Methods: fos genes were searched for in 55 E. coli strains collected from seven representative hospitals located in Madrid. A phenotypic screening test was performed following the disk diffusion method with sodium phosphonoformate added as described by Nakamura et al. Additionally, a molecular study based on PCR was used to confirm the screening results. Positive strains for fos genes were further subjected to whole-genome sequencing (WGS). Results: Phenotypic screening was positive in 9/55 strains (16.4%), although genotypic detection was positive in only 3 (fosA3, fosA4 and fosA6). Thus, the prevalence of fos genes in Madrid was 5.5% (3/55). WGS data were not available for the fosA6-positive strain. One isolate with fosA3 (ST69) carried a blaCTX-M-55 gene and seven virulence genes (air, eilA, iha, iss, lpfA, sat and senB). The fosA4-positive isolate (ST4038) carried the virulence genes iss, lpfA, iroN and mchF. Both fos genes were located between two IS26 mobile elements of a plasmid. Conclusion: We detected the presence of different variants of plasmid-mediated fosA genes in fosfomycin-resistant E. coli strains in Madrid, Spain. Despite the few reports in Europe, it would be of interest to monitor the spread of these acquired resistance genes.

Background: Often, therapeutic decision-making in breast cancer (BC) patients is deeply influenced by age, with young women receiving highly aggressive systemic therapy, even when low clinical risk features are present. Currently, genomic signature studies have included a limited number of young patients, thus hindering their use in this population. Furthermore, significant data about their impact on clinical decision-making is lacking. Consequently, the medical community should strive to identify young patients who would not benefit from chemotherapy (CT). The aim of this prospective study was to determine the impact of the EndoPredict assay on adjuvant decision-making by a multidisciplinary team in premenopausal women. Patients and method: A total of 92 premenopausal women with hormone receptor-positive, HER2 negative, T1-T2, and N0-N1 BC have been included. Clinicopathological characteristics were recorded and each case presented in a multidisciplinary tumor board. Consensual therapeutic decisions before and after EndoPredict results were registered. Pearson chi-square was used to analyze differences between groups. Results: Median age at diagnosis was 43.5 years (y), with 68% being ≤ 45y. 28% had node-positive disease. Stage at diagnosis was: I (40%), IIA (36%), and IIB (23%). 11%, 72%, and 10% of tumors were low-, intermediate-, or high-grade, respectively. A total of 39 patients (46%) had a low-risk EPclin result. Notably, 61% of patients in the N0 group had a low-risk result compared to 9% with N1 status (p Change in CT decision was recorded in 14/85 patients (17%), with the greatest impact in CT reduction (table 1). Furthermore, 22/85 (26%) and 19/85 (22%) had a change in CT and anti-hormonal therapy regimen, respectively. Overall therapeutic compliance with EndoPredict results was 95%: 100% of patients with a high-risk EPclin received CT, while 87% with a low-risk result did not. Table 1.Pre- and Post-EndoPredict CT consensus Post-TestPost-Test No CTCTTotalPre-TestNo CT24 (28%)4 (5%)28 (33%)Pre-TestCT10 (12%)47 (55%)57 (67%) Total34 (40%)51 (60%)85 (100%) Conclusions: This is the first study that evaluates the EndoPredict assay effect in decision-making in a premenopausal BC patient cohort. The less overall therapy change observed, compared to previous studies, could be the result of a reliable clinical judgment for identifying high-risk patients, which represent a large proportion in this young group. Overall, the test's greatest impact was aiding the discrimination of patients that would not benefit from CT, thus avoiding unnecessary adverse effects. In conclusion, the EndoPredict test successfully assisted the clinical decision-making process in premenopausal patients, with a high rate of therapeutic compliance and a significant change in overall decision. Citation Format: Villarreal-Garza C, Deneken-Hernandez Z, Maffuz-Aziz A, Lopez-Martinez EA, Muñoz-Lozano JF, Barragan-Carrillo R, Peña-Curiel O, Moreno B, Ramos-Elias P, Diaz H, Bautista-Piña V. Change in therapeutic management after EndoPredict assay in a prospective decision impact study of Mexican premenopausal patients [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-08-54.

Secretory breast carcinoma was first described by McDivitt and Stewart in 1966, who reported seven cases of this tumoural strain in children and therefore named it “juvenile carcinoma”. However, a couple of decades later, Tavassoli and Norris reported a series of 19 cases and found that most occurred in adults, and therefore they proposed changing its name to “secretory carcinoma.” Since then, approximately 100 cases have been reported in the world literature. We present two cases treated with total mastectomy and sentinel node biopsy with excellent outcome. To our knowledge, only a few cases have been reported in Latin American patients.

Objective To evaluate the change in adjuvant therapeutic decision in a cohort of young women with breast cancer discussed by a multidisciplinary team, before and after EndoPredict testing. Patients and methods 99 premenopausal women with hormone receptor-positive, HER2-negative, T1-T2, and N0-N1 breast cancer were included. Clinicopathological characteristics were recorded and cases were presented in a multidisciplinary tumor board. Consensual therapeutic decisions before and after EndoPredict results were registered. Medical records were reviewed at six-month follow-up to determine physicians’ adherence to therapeutic recommendations. Pearson chi-square and McNemar’s tests were used to analyze differences between groups and changes in treatment recommendations, respectively. Results Median age at diagnosis was 43 years. The most frequent tumor size was pT2 (53.5%) and 27% of patients had 1–3 positive lymph nodes. 46% of patients had a low-risk EPclin result. Nodal status and tumor grade were significantly associated with EPclin result (p < .00001 and p = .0110, respectively), while Ki67 levels and age ≤40 years were not. A change in chemotherapy decision was registered in 19.2% of patients (p = .066), with the greatest impact in de-escalation (9% net reduction). A change in chemotherapy or endocrine therapy regimen was suggested in 19% and 20% of cases, respectively, after EPclin results were available. A significant difference was found in the median EPclin score between patients with a low- vs. high-intensity chemotherapy and endocrine therapy regimen recommendation (p = 0.049 and p = 0.0001, respectively). Tumor board treatment recommendation adherence with the EndoPredict result was 95% and final treatment adherence to EPclin result was 93%. Conclusions The EndoPredict test successfully assisted the clinical decision-making process in premenopausal patients, with a clinically significant change in overall decision-making, with the greatest impact seen in chemotherapy reduction, and a high rate of therapeutic adherence.

Antibiotic resistance is a global threat of complex and changeable epidemiology. The role of wild birds in the dissemination of antibacterial resistance might be underestimated. We studied the cloacal colonization by cefotaxime-resistant Enterobacteriaceae in 668 wild birds in Spain. Eighty-eight wild birds (13.2%) of 28 species carried cefotaxime-resistant isolates; 58 of them (8.7%) carried extended-spectrum β-lactamases (ESBLs) and 15 (2.5%) plasmid-mediated AmpCs of the bla

Carbapenemase-producing (CP) Pseudomonas aeruginosa is rare compared with mutation-driven carbapenem-resistance, but this situation may be changing. A collection of CP P. aeruginosa isolates was characterized in this study. In 2016, 232 unduplicated carbapenem-resistant P. aeruginosa isolates, of which 71 (30.6%) carried carbapenemase genes, were submitted to the Spanish antibiotic reference laboratory and were further analysed by whole-genome sequencing (WGS). Of the 71 CP P. aeruginosa, 39 (54.9%) carried bla

Carbapenemase-producing (CP) Pseudomonas aeruginosa is rare compared with mutation-driven carbapenem-resistance, but this situation may be changing. A collection of CP P. aeruginosa isolates was characterized in this study. In 2016, 232 unduplicated carbapenem-resistant P. aeruginosa isolates, of which 71 (30.6%) carried carbapenemase genes, were submitted to the Spanish antibiotic reference laboratory and were further analysed by whole-genome sequencing (WGS). Of the 71 CP P. aeruginosa, 39 (54.9%) carried blaVIM-2, 14 (19.7%) blaVIM-1, 8 (11.3%) blaIMP-8, 6 (8.5%) blaVIM-20, 2 (2.8%) blaVIM-2 plus blaKPC-2, one (1.4%) blaIMP-13 and one (1.4%) blaVIM-1 plus blaIMP-18. Four sequence types (ST175, ST244, ST815 and ST155) encompassed 83.1% of the 71 CP P. aeruginosa; ST175 was detected in hospitals from seven provinces. Using core genome multilocus sequence typing (cgMLST), four clusters were detected: Cluster 1 included nine ST815/VIM-2 isolates; Cluster 2 included five ST175/VIM-2 isolates; Cluster 3 included seven ST244 isolates (five VIM-2 and two VIM-2 plus KPC-2); and Cluster 4 included 11 ST175 isolates (seven VIM-2 and four IMP-8). The average number of acquired resistance genes was significantly higher in the blaVIM-1-carying isolates (7.1 ± 0.94) than in the blaVIM-2-carrying isolates (4.5 ± 0.20). CP P. aeruginosa isolates are spreading in Spain, mainly due to the dissemination of high-risk clones such as ST175 and ST244 producing VIM and IMP carbapenemases. Emergence of CP P. aeruginosa is a cause of clinical and epidemiological concern.

The emergence of linezolid-resistant Enterococcus spp. (LRE) due to transferable resistance determinants is a matter of concern. To understand the contribution of the plasmid-encoded optrA and poxtA genes to the emergence of LRE, clinical isolates from different Spanish hospitals submitted to the Spanish Reference Laboratory from 2015-2018 were analysed. Linezolid resistance mechanisms were screened in all isolates by PCR and sequencing. Genetic relatedness of Enterococcus spp. carrying optrA and poxtA was studied by PFGE and MLST. Antimicrobial susceptibility was tested by broth microdilution using EUCAST standards. A total of 97 LRE isolates were studied, in 94 (96.9%) of which at least one resistance determinant was detected; 84/97 isolates (86.6%) presented a single resistance mechanism as follows: 45/84 (53.6%) carried the optrA gene, 38/84 (45.2%) carried the G2576T mutation and 1/84 (1.2%) carried the poxtA gene. In addition, 5/97 isolates (5.2%) carried both optrA and the G2576T mutation and 5/97 (5.2%) carried both optrA and poxtA. The optrA gene was more frequent in Enterococcus faecalis (83.6%) than Enterococcus faecium (11.1%) and was mainly associated with community-acquired urinary tract infections. Carriage of the poxtA gene was more frequent in E. faecium (13.9%) than E. faecalis (1.6%). Among the optrA-positive E. faecalis isolates, two main clusters were detected by PFGE. These two clusters belonged to ST585 and ST480 and were distributed throughout 11 and 6 Spanish provinces, respectively. This is the first description of LRE carrying the poxtA gene in Spain, including the co-existence of optrA and poxtA in five isolates.

Breast cancer is a heterogeneous pathology, but the genomic basis of its variability remains poorly understood in populations other than Caucasians. Here, through DNA and RNA portraits we explored the molecular features of breast cancers in a set of Hispanic-Mexican (HM) women and compared them to public multi-ancestry datasets. HM patients present an earlier onset of the disease, particularly in aggressive clinical subtypes, compared to non-Hispanic women. The age-related COSMIC signature 1 was more frequent in HM women than in those from other ancestries. We found the AKT1E17K hotspot mutation in 8% of the HM women and identify the AKT1/PIK3CA axis as a potentially druggable target. Also, HM luminal breast tumors present an enhanced immunogenic phenotype compared to Asiatic and Caucasian tumors. This study is an initial effort to include patients from Hispanic populations in the research of breast cancer etiology and biology to further understand breast cancer disparities., Cancers in different populations have been shown to be genetically distinct. Here, the authors sequence breast cancers from Mexican-Hispanic patients and find that these patients have a higher percentage of Akt1 mutations compared to Caucasian and Asian populations, suggesting these are clinically actionable.

Breast cancer is the most commonly diagnosed neoplasm in women worldwide with a well-recognized heterogeneous pathology, classified into four molecular subtypes: Luminal A, Luminal B, HER2-enriched and Basal-like, each one with different biological and clinical characteristics. Long non-coding RNAs (lncRNAs) represent 33% of the human transcriptome and play critical roles in breast carcinogenesis, but most of their functions are still unknown. Therefore, cancer research could benefit from continued exploration into the biology of lncRNAs in this neoplasm. We characterized lncRNA expression portraits in 74 breast tumors belonging to the four molecular subtypes using transcriptome microarrays. To infer the biological role of the deregulated lncRNAs in the molecular subtypes, we performed co-expression analysis of lncRNA–mRNA and gene ontology analysis. We identified 307 deregulated lncRNAs in tumor compared to normal tissue and 354 deregulated lncRNAs among the different molecular subtypes. Through co-expression analysis between lncRNAs and protein-coding genes, along with gene enrichment analysis, we inferred the potential function of the most deregulated lncRNAs in each molecular subtype, and independently validated our results taking advantage of TCGA data. Overexpression of the AC009283.1 was observed in the HER2-enriched subtype and it is localized in an amplification zone at chromosome 17q12, suggesting it to be a potential tumorigenic lncRNA. The functional role of lncRNA AC009283.1 was examined through loss of function assays in vitro and determining its impact on global gene expression. These studies revealed that AC009283.1 regulates genes involved in proliferation, cell cycle and apoptosis in a HER2 cellular model. We further confirmed these findings through ssGSEA and CEMITool analysis in an independent HER2-amplified breast cancer cohort. Our findings suggest a wide range of biological functions for lncRNAs in each breast cancer molecular subtype and provide a basis for their biological and functional study, as was conducted for AC009283.1, showing it to be a potential regulator of proliferation and apoptosis in the HER2-enriched subtype.

Introduction Patients with similar local advanced breast cancer (LABC) could respond different to neoadjuvant chemotherapy (NC). Luminal HER2(-) tumors have pathologic complete response (pCR) by 5-7%. Ki67, tumor grade and hormonal receptors, could be helpful but not enough to choice between NC vs. initial surgery. Response to drugs depends on enzymes involved in absorption, distribution, metabolism and elimination (ADME); the drug-metabolizing enzyme and transporter platform (DMET), could identify 1936 single nucleotide polymorphism (SNP) from 225 genes involved in ADME proccess. Objective To identify predictive factors to pCR in patients with Luminal HER2(-) LABC underwent NC, to distinguish wish patients could have a real benefit from NC. Material and Methods This is a prospective nested case control study (1:4) with LABC patients, pure invasive ductal carcinoma Luminal HER2(-) subtypes, and sequential NC (anthracyclines and taxanes). Cases were defined as patients with pCR (Residual Cancer Burden=0), and controls those without pCR. SNPs were evaluated from DNA of leucocytes using DMET microarrays by Affymetrix. Bivariate analyses were used as appropriate. Microarrays were processed by the DMET analyzer console. OR and 95%CI were used to test association between pCR and variables with a non-conditional logistic regression analysis; p value ≤0.05 was considered statistically significant (two-sided). Results From 2005 to 2014, of 3762 treated patients, 287 women met inclusion criteria. We included 117 patients, 21 cases and 96 controls. Patients with pCR were 5 years younger than controls (45.4 vs 49.4), have more grade-3 tumors, (66.7 vs 22.3%), more Luminal B subtypes (90.5 vs 64.6%), lower expression of estrogen receptor (60 vs 80%) and higher Ki67 expression (65 vs 12%), all with p≤0.05. No differences in toxicity existed between groups. In an initial screening procedure, 13 SNPs were identified, but only 4 SNPs (4 genes) are known to participate in ADME of antineoplastic agents. All pCR cases did not have the C/C allelic variant in the rs2072671 SNP (CDA gene); while in rs1883322 SNP (PPARD gene) all had T/T variant SNPs identified in DMET microarray known to participate with antineoplastic agentsGENESNPAllelic variantpCR, n=21No pCR, n=96pDPYDrs17376848T/T13 (61.9%)83 (86.4%)0.007 C/T8 (38.1%)11 (11.4%) CDArs2072671A/A6 (28.5%)51 (53.1%)0.013 A/C15 (71.4%)36 (37.5%) C/C09 (9.3%) PPARDrs1883322T/T21 (100%)69 (71.8%)0.022 C/T022 (22.9%) C/C05 (5.2%) GSTM3rs7483A/A7 (33.3%)20 (20.8%)0.024 A/G13 (61.9%)43 (44.7%) G/G1 (4.7%)33 (34.3%) pCR= pathologic complete response After logistic regression analysis, pCR predictive factors were the presence of grade-3 tumors OR=6.66 (95%CI=1.67-26.56), Ki67 ≥14% OR=15.45 (95%CI=1.71–138.86), premenopausal status OR=6.540 (95%CI=1.50–28.38) and A/A or A/G allele in rs7483 SNP (GSTM3 gene) OR=19.16 (95%CI=1.97–185.93). Conclusions Genetic variability encoded in the DMET-chip, could be helpful as a predictive factor of pCR in patients with Luminal HER2(-) LABC, but only in combination with other factors such as grade-3 tumors, elevated Ki67, and premenopausal status. Citation Format: Ruvalcaba-Limon E, Rodriguez-Cuevas S, Hidalgo-Miranda A, Villa-Romero A, Bautista-Piña V, Rebollar-Vega R, Fernandez-Lopez JC, Morales-Vasquez F. Predictive factors of pathologic complete response to neoadjuvant chemotherapy in patients with Luminal HER2(-) local advanced breast cancer using the DMET microarray [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P6-09-18.

Objectives We analysed the microbiological traits and population structure of KPC-producing Enterobacteriaceae isolates collected in Spain between 2012 and 2014. We also performed a comparative WGS analysis of the three major KPC-producing Klebsiella pneumoniae clones detected. Methods Carbapenemase and ESBL genes were sequenced. The Institut Pasteur MLST scheme was used. WGS data were used to construct phylogenetic trees, to identify the determinants of resistance and to de novo assemble the genome of one representative isolate of each of the three major K. pneumoniae clones. Results Of the 2443 carbapenemase-producing Enterobacteriaceae isolates identified during the study period, 111 (4.5%) produced KPC. Of these, 81 (73.0%) were K. pneumoniae and 13 (11.7%) were Enterobacter cloacae. Three major epidemic clones of K. pneumoniae were identified: ST11/KPC-2, ST101/KPC-2 and ST512/KPC-3. ST11/KPC-2 differed from ST101/KPC-2 and ST512/KPC-3 by 27 819 and 6924 SNPs, respectively. ST101/KPC-2 differed from ST512/KPC-3 by 28 345 SNPs. Nine acquired resistance genes were found in ST11/KPC-2, 11 in ST512/KPC-3 and 13 in ST101/KPC-2. ST101/KPC-2 had the highest number of virulence genes (20). An 11 bp deletion at the end of the mgrB sequence was the cause of colistin resistance in ST512/KPC-3. Conclusions KPC-producing Enterobacteriaceae are increasing in Spain. Most KPC-producing K. pneumoniae isolates belonged to only five clones: ST11 and ST512 caused interregional spread, ST101 caused regional spread and ST1961 and ST678 produced independent hospital outbreaks. ST101/KPC-2 had the highest number of resistance and virulence genes. ST101/KPC-2 and ST512/KPC-3 were recently implicated in the spread of KPC in Italy.

OBJECTIVES The objective of this study was to analyse the microbiological traits and the population structure of carbapenemase-producing (CP) Escherichia coli isolates collected in Spain between 2012 and 2014. METHODS Two-hundred-and-thirty-nine E. coli isolates non-susceptible to carbapenems were studied. The carbapenemase genes and the phylogenetic groups were characterized using PCR. MLST was carried out using the typing schemes of the University of Warwick and the Institut Pasteur. The diversity of the population structure was estimated by calculating a simple diversity index (SDI). RESULTS One-hundred-and-twenty-one isolates (50.6%) produced carbapenemases, of which 87 (71.9%) were OXA-48, 27 (22.3%) were VIM-1, 4 (3.3%) were KPC-2, 2 (1.7%) were NDM and 1 (0.8%) was IMP-22; 4 isolates were collected in 2012, 40 in 2013 and 77 in 2014. Ertapenem was more sensitive than imipenem or meropenem for screening for OXA-48-producing E. coli. Using the Warwick typing scheme, 59 different STs were identified, the most prevalent being ST131 (16.5%). The population diversity was higher among VIM-1-producing isolates (SDI = 81.5%) than among OXA-48-producing isolates (SDI = 44.8%). The Pasteur scheme had a higher discrimination capability (SDI = 55.4%) than the Warwick scheme (SDI = 48.8%). CONCLUSIONS A progressive increase in the prevalence of CP E. coli was observed, mainly due to the dissemination of OXA-48 producers. The most sensitive method for detecting decreased susceptibility of CP E. coli to carbapenems was disc diffusion with ertapenem using the EUCAST screening cut-offs. The spread of CP E. coli was due to a polyclonal population. The Pasteur scheme showed the highest discrimination power. Surveillance is crucial for the early detection of CP E. coli.

Objectives NDM carbapenemases have spread worldwide. However, little information exists about the impact of NDM-producing Enterobacteriaceae in Spain. By WGS, we sought to elucidate the population structure of NDM-like-producing Klebsiella pneumoniae and Escherichia coli in Spain and to determine the plasmids harbouring blaNDM-like genes. Methods High-resolution SNP typing, core-genome MLST and plasmid reconstruction (PlasmidID) were performed on 59 NDM-like-producing K. pneumoniae and 8 NDM-like-producing E. coli isolated over an 8 year period in Spain. Results Five major epidemic clones of NDM-producing K. pneumoniae caused five important nationwide outbreaks: ST437/NDM-7, ST437/NDM-1, ST147/NDM-1, ST11/NDM-1 and ST101/NDM-1; in contrast, the spread of NDM-producing E. coli was polyclonal. Three blaNDM types were identified: blaNDM-1, 61.2%; blaNDM-7, 32.8%; and blaNDM-5, 6%. Five K. pneumoniae isolates co-produced other carbapenemases (three blaOXA-48 and two blaVIM-1). The average number of acquired resistance genes was higher in K. pneumoniae than in E. coli. The plasmids encoding blaNDM-like genes belonged to IncFII, IncFIB, IncX3, IncR, IncN and IncC types, of which IncF, IncR and IncC were associated with MDR. The genetic surroundings of blaNDM-like genes showed a highly variable region upstream of ISAba125. Conclusions In recent years NDM-producing K. pneumoniae and E. coli have emerged in Spain; the spread of a few high-risk K. pneumoniae clones such as ST437/NDM-7, ST437/NDM-1, ST147/NDM-1, ST11/NDM-1 and ST101/NDM-1 have caused several interregional outbreaks. In contrast, the spread of NDM-producing E. coli has been polyclonal. Plasmid types IncFII, IncFIB, IncX3, IncR, IncN and IncC carried blaNDM, and the same IncX3 plasmid was detected in K. pneumoniae and E. coli.

Interpretation of variants of unknown significance (VUS) in genetic tests is complicated in ethnically diverse populations, given the lack of information regarding the common spectrum of genetic variation in clinically relevant genes. Public availability of data obtained from high-throughput genotyping and/or exome massive parallel sequencing (MPS)-based projects from several thousands of outbred samples might become useful tools to evaluate the pathogenicity of a VUS, based on its frequency in different populations. In the case of the Mexican and other Latino populations, several thousands of samples have been genotyped or sequenced during the last few years as part of different efforts to identify common variants associated to common diseases. In this report, we analyzed Mexican population data from a sample of 3985 outbred individuals, and additional 66 hereditary breast cancer patients were analyzed in order to better define the spectrum of common genomic variation of the BRCA1 and BRCA2 genes. Our analyses identified the most common genetic variants in these clinically relevant genes as well as the presence and frequency of specific pathogenic mutations present in the Mexican population. Analysis of the 3985 population samples by MPS identified three pathogenic mutations in BRCA1, only one population sample showed a BRCA1 exon 16–17 deletion by MLPA. This resulted in a basal prevalence of deleterious mutations of 0.10% (1:996) for BRCA1 and 11 pathogenic mutations in BRCA2, resulting in a basal prevalence of deleterious mutations of 0.276% (1:362) for BRCA2, combined of 0.376% (1:265). Separate analysis of the breast cancer patients identified the presence of pathogenic mutations in 18% (12 pathogenic mutations in 66 patients) of the samples by MPS and 13 additional alterations by MLPA. These results will support a better interpretation of clinical studies focused on the detection of BRCA mutations in Mexican and Latino populations and will help to define the general prevalence of deleterious mutations within these populations. Electronic supplementary material The online version of this article (10.1186/s40246-018-0188-9) contains supplementary material, which is available to authorized users.

Triple negative breast cancer (TNBC) represents an aggressive phenotype with poor prognosis compared with ER, PR, and HER2‐positive tumors. TNBC is a heterogeneous disease, and gene expression analysis has identified seven molecular subtypes. Accumulating evidence demonstrates that long non‐coding RNA (lncRNA) are involved in regulation of gene expression and cancer biology, contributing to essential cancer cell functions. In this study, we analyzed the expression profile of lncRNA in TNBC subtypes from 156 TNBC samples, and then characterized the functional role of LncKLHDC7B (ENSG00000226738). A total of 710 lncRNA were found to be differentially expressed between TNBC subtypes, and a subset of these altered lncRNA were independently validated. We discovered that LncKLHDC7B (ENSG00000226738) acts as a transcriptional modulator of its neighboring coding gene KLHDC7B in the immunomodulatory subtype. Furthermore, LncKLHDC7B knockdown enhanced migration and invasion, and promoted resistance to cellular death. Our findings confirmed the contribution of LncKLHDC7B to induction of apoptosis and inhibition of cell migration and invasion, suggesting that TNBC tumors with enrichment of LncKLHDC7B may exhibit distinct regulatory activity, or that this may be a generalized process in breast cancer. Additionally, in silico analysis confirmed for the first time that the low expression of KLHDC7B and LncKLHDC7B is associated with poor prognosis in patients with breast cancer.

Triple-negative breast cancer (TNBC) is a heterogeneous and aggressive neoplasia lacking the expression of hormonal receptors and human epidermal growth factor receptor-2. Accumulating evidence has highlighted the importance of miRNAs dysregulation in the establishment of cancer programs, but the functional role of many miRNAs remains unclear. The description of miRNAs roles might provide novel strategies for treatment. In the present work, an integrated analysis of miRNA transcriptional landscape was performed (N = 132), identifying the significant down-modulation of miR-342-3p in TNBC, probably because of the aberrant activity of estrogen receptor, which serves as a transcription factor of the miRNA, as demonstrated by a siRNA-knockdown approach. The enhanced expression of miR-342-3p significantly decreased cell proliferation, viability and migration rates of diverse TN cells in vitro. Bioinformatic and functional analyses revealed that miR-342-3p directly targets the monocarboxylate transporter 1 (MCT1), which promotes lactate and glucose fluxes alteration, thus disrupting the metabolic homeostasis of tumor cells. Optical metabolic imaging assay defined a higher optical redox ratio in glycolytic cells overexpressing miR-342-3p. Furthermore, we found that hypoxic conditions and glucose starvation attenuate miR-342-3p expression, suggesting a crosstalk program between these metabolic factors. Consistently, miR-342-3p down-modulation is associated with an increased MCT1 expression level and glycolytic score in human triple negative tumors. Overall, we described for the first time the regulatory activity of miR-342-3p on relevant metabolic carcinogenic pathways in TN breast cancers.

Background. Immune response seems to improve outcome in women with Triple-Negative Breast Cancer (TNBC). Recent data suggests that the presence of Tumor-Infiltrating Lymphocytes (TIL's) is an independent factor associated with favorable prognosis. In this study, we evaluate the prognostic impact of both the TIL's and SIL's in patients with TNBC. Methods. Data on women diagnosed with triple negative breast cancer between 2005 and 2013, was collected by retrospectively reviewing at Breast Disease Institute, FUCAM. The rate of intratumoral and/or stromal lymphocytes was evaluated in all histopathologic biopsies according to Denkert et al. Lymphocyte infiltrate was assessed in hematoxylin and eosin-stained sections. TIL's were reported as the percentage of tumor epithelial nests containing infiltrating lymphocytes, while SIL's as the percentage of stroma area with lymphocytic infiltrate without contact with tumor cells. The five-year disease-free survival (DFS) and overall survival (OS) were compared between groups with the presence or absence of Tumor-Infiltrating Lymphocytes or Stromal-Infiltrating Lymphocytes. Demographic and clinical characteristics were assessed, and the variables with a statistically significant difference between groups were analyzed in a multivariate analysis. Results. A total of 172 patients with Triple-Negative breast cancer treated this institution were included with a mean age of 49.8 years. A complete absence of tumor lymphocytes was found in 88 patients while the presence of intratumoral, stromal or both was found in 84 (48.8%). A mean follow-up of 46.12 months showed significantly higher rates of both disease-free survival and overall survival in women with SIL's and TIL's (p = 0.014 and 0.042 respectively) in locally advanced stages (LAS), regardless the rate of infiltrating lymphocytes found. 5-year Overall Survival in Locally Advanced Stages Overall SurvivalpNegative48.7 ± 7.8 SIL´s74.2 ± 6.60.014TIL ´s69.2 ± 7.30.042Table 1. Statistical significance was defined as p < 0.05. In these patients, Stromal Lymphocytes are strongly correlated with a better prognosis compared with Intratumoral Lymphocytes. Multivariate analysisVariables with statistical significanceβ ValuepSIL´s4.8460.028TIL ´s2.8500.091Table 2. Multivariate analysis. Statistical significance was defined as p = 0.10 Non-significant differences were found in early stages (p = 0.255). Conclusion. Immunity seems to play a key role regarding the outcome in women with Triple-Negative Breast Cancer. We show that the presence of SIL's or TIL's are strongly associated with higher rates of disease-free and overall survival in LAS, especially when stromal lymphocytes are found. Independent to the rate of lymphocytic infiltrate, its presence has a statistical significance. Because it is a feasible, reproducible and inexpensive test that can be used as a prognostic predictor, we recommend assessing both SIL's and TIL's histopathologic biopsies of patients with TNBC. Citation Format: Sherwell-Cabello S, Maffuz-Aziz A, Bautista-Piña V, Labastida-Almendaro S, Camacho-Ramírez DA, Ríos-Luna NP, Rodríguez-Cuevas S. Prognostic impact of tumor-infiltrating lymphocytes (TIL's) and stromal-infiltrating lymphocytes (SIL's) in triple negative breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P2-08-04.

We found a low prevalence (0.6%) of carbapenemase-producing Enterobacteriaceae (CPE) in fecal microbiota of companion dogs. A single VIM-1-producing Klebsiella pneumoniae isolate belonging to sequence type (ST) 2090 was detected. bla VIM-1 was carried on a class 1 integron and an untypeable ∼48-kb plasmid. Emergence and spread of CPE in this group of animals may be a threat to public health in human and veterinary medicine. This finding supports the need for active surveillance studies in companion animals that live close to humans, as interspecies transmission may occur within the same household.