Effect of mammography screening on surgical treatment for breast cancer in Norway: comparative analysis of cancer registry data

Objective To determine the effect of mammography screening on surgical treatment for breast cancer

Predictive and Prognostic Impact of TP53 Mutations and MDM2 Promoter Genotype in Primary Breast Cancer Patients Treated with Epirubicin or Paclitaxel

Background: TP53 mutations have been associated with resistance to anthracyclines but not to taxanes in breast cancer patients. The MDM2 promoter single nucleotide polymorphism (SNP) T309G increases MDM2 activity and may reduce wildtype p53 protein activity. Here, we explored the predictive and prognostic value of TP53 and CHEK2 mutation status together with MDM2 SNP309 genotype in stage III breast cancer patients receiving paclitaxel or epirubicin monotherapy. Experimental Design: Each patient was randomly assigned to treatment with epirubicin 90 mg/m2 (n= 109) or paclitaxel 200 mg/m2 (n = 114) every 3rd week as monotherapy for 4–6 cycles. Patients obtaining a suboptimal response on first-line treatment requiring further chemotherapy received the opposite regimen. Time from last patient inclusion to follow-up censoring was 69 months. Each patient had snap-frozen tumor tissue specimens collected prior to commencing chemotherapy. Principal Findings: While TP53 and CHEK2 mutations predicted resistance to epirubicin, MDM2 status did not. Neither TP53/ CHEK2 mutations nor MDM2 status was associated with paclitaxel response. Remarkably, TP53 mutations (p = 0.007) but also MDM2 309TG/GG genotype status (p = 0.012) were associated with a poor disease-specific survival among patients having paclitaxel but not patients having epirubicin first-line. The effect of MDM2 status was observed among individuals harbouring wild-type TP53 (p = 0.039) but not among individuals with TP53 mutated tumors (p.0.5). Conclusion: TP53 and CHEK2 mutations were associated with lack of response to epirubicin monotherapy. In contrast, TP53 mutations and MDM2 309G allele status conferred poor disease-specific survival among patients treated with primary paclitaxel but not epirubicin monotherapy

Propuesta de gestión logística en los almacenes de repuestos de la Distribuidora Santa Mónica S.A.C para reducir sus costos operacionales

RESUMEN La presente tesis es un trabajo de investigación que se enfoca en desarrollar un sistema de gestión logística en los almacenes de repuestos de una distribuidora, que incluye la adquisición, recepción, almacenamiento y correcta entrega de mercadería a los diversos clientes. El conocimiento y aplicación de indicadores y/o métodos permitirá administrar y gestionar; además será el inicio de una serie de acciones a realizar orientadas hacia la mejora continua. Las exigencias de los clientes respecto a la rápida atención de sus requerimientos son cada vez mayores, asimismo el mercado exige ser bastante competitivo en costos, por lo cual un elemento diferenciador, será el analizar la mejora en los procesos logísticos y eliminar todo lo que no genera valor, e identificar y eliminar las causas con la finalidad de automatización de procesos y reducción de los costos operacionales. Finalmente la gestión logística en los almacenes propuesto permite la fácil coordinación de información y distribución dentro del almacén que supera las expectativas del mercado local en una distribuidora generando un impacto positivo en la viabilidad económica tal como: VAN S/. 510,601.54 y TIR 107.37%, adicionalmente se logró desarrollar actividades logísticas de la empresa como: disminución de pérdidas en un 85%, aumento de atenciones a clientes y mayor rapidez del mismo en un 46% y disminución de pedidos en un 35%. Asimismo tiene como ventajas: validar información de proveedores, disminuir niveles de inventario, agilizar rotación artículos y coordinar efectivamente al personal.ABSTRACT The present thesis is a work of investigation that focuses in developing a system of logistic management in the repair parts stocks of a distributor, who includes the acquisition, reception, storage and correcto delivery of merchandise to the diverse clients. The knowledge and application of indicators and/or methods will allow to administer and to manage; in addition it will be the beginning of a series of action to realice oriented towards the continuous improvement. The exigencies of the clients with respect to the fast attention of their requirements are very time majors, also the market demands to be quite competitive in costs, thus an element differentiator, the improvement in the logistic processes will be to analyze and to eliminate everything what it does not generate value, and to identify and to eliminate the causes for the purposes of automatization of processes and reduction of the operational costs. Finally the logistic management in the warehouses proposed allows the easy coordination of information and distribution within the warehouse that surpasses the expectations of the local market in a distributor generating a positive impact in the economic viability as: VAN S/. 510,601.54 and TIR 107.37%, additionally were managed to develop logistics operations of the Company like: diminution of losses in a 85%, increase of attentions in clients and major rapidity of the same in a 46% and diminution of orders in a 35%. Also it has like advantages: to validate information of suppliers, to diminish inventory levels, to make agile rotation articles and to indeed coordinate the personnel

Insulin-like growth factor-1, growth hormone, and daily cycling estrogen are associated with mammographic density in premenopausal women

Background: Mammographic density represents epithelial and stromal proliferation, while Insulin-like growth factor (IGF)-1, IGF-binding protein (IGFBP)-3, growth hormone (GH) and estrogen, may influence cellular proliferation. However, whether these growth factors independently, or in combination with estrogen, influence mammographic density in premenopausal women remains unclear. Material and methods: Growth factors were assessed in 202 ovulating premenopausal women participating in the Energy Balance and Breast cancer Aspects (EBBA)-I study. Estrogen was assessed in serum, and daily in saliva, throughout a menstrual cycle. Computer-assisted mammographic density (Madena) was obtained from digitized mammograms (days 7-12 of the menstrual cycle). Associations between growth factors, estrogen and percent mammographic density, were studied in regression models. Results: Women with a mean age of 30.7 years had a mean percent mammographic density of 29.8%. Among women in the strata (above median split) of IGF-1 (>25 nmol/l) or GH (>0.80 mlU/l), we observed that an increase in salivary 17β–estradiol, was associated with a higher odds for having higher percent mammographic density (>28.5 %). The odds ratios (ORs) per standard deviation increase of 17β-estradiol, were 1.81 (95% confidence interval [CI] 1.08-3.03) in the high IGF-1 stratum, and 2.08 (95% CI 1.10-3.94) in the high GH stratum. Furthermore, women in this strata of growth factors (above median) who had an overall average 17β–estradiol above median (>16.8 pmol/l), had higher ORs for having higher percent mammographic density (>28.5%): IGF-1 4.13 (95% CI 1.33-12.83), and GH 4.17 (95% CI 1.41-12.28). Conclusion: Growth factors, in combination with cycling estrogen, were associated with percent mammographic density, of potential clinical relevance.Anthropolog

Surgical Management of the Axilla in Clinically Node-Positive Breast Cancer Patients Converting to Clinical Node Negativity through Neoadjuvant Chemotherapy : Current Status, Knowledge Gaps, and Rationale for the EUBREAST-03 AXSANA Study

In the last two decades, surgical methods for axillary staging in breast cancer patients have become less extensive, and full axillary lymph node dissection (ALND) is confined to selected patients. In initially node-positive patients undergoing neoadjuvant chemotherapy, however, the optimal management remains unclear. Current guidelines vary widely, endorsing different strategies. We performed a literature review on axillary staging strategies and their place in international recommendations. This overview defines knowledge gaps associated with specific procedures, summarizes currently ongoing clinical trials that address these unsolved issues, and provides the rationale for further research. While some guidelines have already implemented surgical de-escalation, replacing ALND with, e.g., sentinel lymph node biopsy (SLNB) or targeted axillary dissection (TAD) in cN+ patients converting to clinical node negativity, others recommend ALND. Numerous techniques are in use for tagging lymph node metastasis, but many questions regarding the marking technique, i.e., the optimal time for marker placement and the number of marked nodes, remain unanswered. The optimal number of SLNs to be excised also remains a matter of debate. Data on oncological safety and quality of life following different staging procedures are lacking. These results provide the rationale for the multinational prospective cohort study AXSANA initiated by EUBREAST, which started enrollment in June 2020 and aims at recruiting 3000 patients in 20 countries (NCT04373655; Funded by AGO-B, Claudia von Schilling Foundation for Breast Cancer Research, AWOgyn, EndoMag, Mammotome, and MeritMedical)

Early detection of breast cancer based on gene-expression patterns in peripheral blood cells

INTRODUCTION: Existing methods to detect breast cancer in asymptomatic patients have limitations, and there is a need to develop more accurate and convenient methods. In this study, we investigated whether early detection of breast cancer is possible by analyzing gene-expression patterns in peripheral blood cells. METHODS: Using macroarrays and nearest-shrunken-centroid method, we analyzed the expression pattern of 1,368 genes in peripheral blood cells of 24 women with breast cancer and 32 women with no signs of this disease. The results were validated using a standard leave-one-out cross-validation approach. RESULTS: We identified a set of 37 genes that correctly predicted the diagnostic class in at least 82% of the samples. The majority of these genes had a decreased expression in samples from breast cancer patients, and predominantly encoded proteins implicated in ribosome production and translation control. In contrast, the expression of some defense-related genes was increased in samples from breast cancer patients. CONCLUSION: The results show that a blood-based gene-expression test can be developed to detect breast cancer early in asymptomatic patients. Additional studies with a large sample size, from women both with and without the disease, are warranted to confirm or refute this finding

Integrative clustering reveals a novel split in the luminal A subtype of breast cancer with impact on outcome

Background: Breast cancer is a heterogeneous disease at the clinical and molecular level. In this study we integrate classifications extracted from five different molecular levels in order to identify integrated subtypes. Methods: Tumor tissue from 425 patients with primary breast cancer from the Oslo2 study was cut and blended, and divided into fractions for DNA, RNA and protein isolation and metabolomics, allowing the acquisition of representative and comparable molecular data. Patients were stratified into groups based on their tumor characteristics from five different molecular levels, using various clustering methods. Finally, all previously identified and newly determined subgroups were combined in a multilevel classification using a "cluster-of-clusters" approach with consensus clustering. Results: Based on DNA copy number data, tumors were categorized into three groups according to the complex arm aberration index. mRNA expression profiles divided tumors into five molecular subgroups according to PAM50 subtyping, and clustering based on microRNA expression revealed four subgroups. Reverse-phase protein array data divided tumors into five subgroups. Hierarchical clustering of tumor metabolic profiles revealed three clusters. Combining DNA copy number and mRNA expression classified tumors into seven clusters based on pathway activity levels, and tumors were classified into ten subtypes using integrative clustering. The final consensus clustering that incorporated all aforementioned subtypes revealed six major groups. Five corresponded well with the mRNA subtypes, while a sixth group resulted from a split of the luminal A subtype; these tumors belonged to distinct microRNA clusters. Gain-of-function studies using MCF-7 cells showed that microRNAs differentially expressed between the luminal A clusters were important for cancer cell survival. These microRNAs were used to validate the split in luminal A tumors in four independent breast cancer cohorts. In two cohorts the microRNAs divided tumors into subgroups with significantly different outcomes, and in another a trend was observed. Conclusions: The six integrated subtypes identified confirm the heterogeneity of breast cancer and show that finer subdivisions of subtypes are evident. Increasing knowledge of the heterogeneity of the luminal A subtype may add pivotal information to guide therapeutic choices, evidently bringing us closer to improved treatment for this largest subgroup of breast cancer.Peer reviewe

Penggunaan Media Gambar Dalam Meningkatkan Kemampuan Membaca Permulaan Siswa Kelas I SDN Uwedaka Kecamatan Pagimana Kabupaten Banggai

Pokok permasalahan dalam penelitian ini adalah rendahnya tingkat kemampuan membaca permulaan siswa kelas I SDN Uwedaka dalam pembelajaran Bahasa Indonesia. Tujuan Penelitian adalah untuk meningkatkan kemampuan membaca permulaan siswa kelas I SDN Uwedaka Kecamatan Pagimana Kabupaten Banggai. Berdasarkan hasil observasi yang didapatkan masih terdapat beberapa siswa yang sama sekali belum bisa membaca. Pembelajaran membaca permulaan di SDN Uwedaka selama ini hanya menggunakan media pembelajaran yang konvensional yaitu dengan menggunakan papan tulis, pembelajaran yang hanya berpusat pada guru, penggunaan media dalam pembelajaran sebagai alat bantu masih sangat terbatas, hal ini menyebabkan kemampuan membaca permulaan yang masih rendah dan terlihat hampir 65% siswa masih mengalami kesulitan membaca dalam proses belajar mengajar. Metode yang digunakan adalah metode deskriptif kualitatif dan kuantitatif. Data kualitatif didapatkan dari hasil tes dan observasi siswa dan guru. data kuantitatif didapatkan dari hasil tes belajar. Desain penelitian ini mengacu pada desain oleh Kemmis dan Mc Taggart yang terdiri dari empat tahapan, yaitu perencanaan, pelaksanaan tindakan, observasi dan refleksi. Data dikumpulkan melalui penilaian proses dan penilaian hasil setiap akhir tindakan. Penelitian ini dilakukan dalam dua siklus. Pada siklus I diperoleh nilai rata-rata siswa yaitu sebesar 67 dengan ketuntasan belajar klasikal sebesar 40% serta daya serap 66,6%. Pada siklus II, nilai rata-rata meningkat menjadi 83 dengan ketuntasan klasikal sebesar 100% serta daya serap klasikal sebesar 83,3%. Bersarkan hasil penelitian maka dapat disimpulkan bahwa penggunaan media gambar dapat meningkatkan kemampuan membaca permulaan terhadap siswa kelas I SDN Uwedaka Kecamatan Pagimana Kabupaten Banggai