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Chen, Wan Qing. "Predictors of Auxillary Lymph Node Involvement in Screen Detected Breast Cancer." Thesis, The University of Sydney, 2004. http://hdl.handle.net/2123/676.
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Background: Axillary lymph node dissection as routine part of breast cancer treatment has been questioned in relation to the balance between benefits and morbidity. The purpose of this study is to determine the association of tumor size, age and histological grade with axillary lymph node metastasis, to determine if some patients could be exempted from axillary dissection. Methods: The data are derived from BreastScreen NSW, the government sponsored population-based breast screening program. In New South Wales (NSW) Australia between 1995 and 2002, 7,221 patients with invasive breast carcinoma were diagnosed and 5,290 patients were eligible for this study. The relationship between incidence of positive axillary lymph nodes and three study factors (tumor size, age and histological grade) was investigated by univariate and multivariate analysis. Logistic regression models were used to predict probability of axillary metastases. Results: The incidence of axillary lymph node metastases was 28.6% (95% CI: 27.4%- 29.8%). Univariate analysis showed that age, tumor size and histological grade were significant predictors of axillary lymph node metastases (p<0.0001). Multivariate analysis identified age, tumor size and histological grade remained as independent predictors (p<0.0001). From multivariate analysis, patients with T1a (Less than or equal to 5mm) and grade I tumors regardless of age had 5.2% (95% CI: 1.2%- 9.3%) frequency of node metastases. Patients 70 years or older with grade I, T1a and T1b (6-10mm) tumors had 4.9% (95% CI: 3.2%- 7.5%) and 6.6% (95% CI: 5.3%-8.3%) predicted frequency of node metastases. Conclusions: Tumor size, age and histological grade are predictors of axillary lymph node metastases. Routine axillary lymph node dissection could be avoided in some patient groups with a low frequency of involved lymph nodes if the benefits are considered to exceed the risks.
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Chen, Wan Qing. "Predictors of Auxillary Lymph Node Involvement in Screen Detected Breast Cancer." University of Sydney. Public Health, 2004. http://hdl.handle.net/2123/676.
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Background: Axillary lymph node dissection as routine part of breast cancer treatment has been questioned in relation to the balance between benefits and morbidity. The purpose of this study is to determine the association of tumor size, age and histological grade with axillary lymph node metastasis, to determine if some patients could be exempted from axillary dissection. Methods: The data are derived from BreastScreen NSW, the government sponsored population-based breast screening program. In New South Wales (NSW) Australia between 1995 and 2002, 7,221 patients with invasive breast carcinoma were diagnosed and 5,290 patients were eligible for this study. The relationship between incidence of positive axillary lymph nodes and three study factors (tumor size, age and histological grade) was investigated by univariate and multivariate analysis. Logistic regression models were used to predict probability of axillary metastases. Results: The incidence of axillary lymph node metastases was 28.6% (95% CI: 27.4%- 29.8%). Univariate analysis showed that age, tumor size and histological grade were significant predictors of axillary lymph node metastases (p<0.0001). Multivariate analysis identified age, tumor size and histological grade remained as independent predictors (p<0.0001). From multivariate analysis, patients with T1a (Less than or equal to 5mm) and grade I tumors regardless of age had 5.2% (95% CI: 1.2%- 9.3%) frequency of node metastases. Patients 70 years or older with grade I, T1a and T1b (6-10mm) tumors had 4.9% (95% CI: 3.2%- 7.5%) and 6.6% (95% CI: 5.3%-8.3%) predicted frequency of node metastases. Conclusions: Tumor size, age and histological grade are predictors of axillary lymph node metastases. Routine axillary lymph node dissection could be avoided in some patient groups with a low frequency of involved lymph nodes if the benefits are considered to exceed the risks.
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Doting, Meintje Hylkje Edwina. "Sentinel lymph node biopsy in breast cancer and melanoma." [S.l. : [Groningen : s.n.] ; University Library Groningen] [Host], 2007. http://irs.ub.rug.nl/ppn/300326254.
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Chen, Wanqing. "Predictors of axillary lymph node involvement in screen-detected breast cancer." Connect to full text, 2004. http://setis.library.usyd.edu.au/adt/public_html/adt-NU/public/adt-NU20050104.165451/index.html.
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Thesis (M.I.P.H.)--School of Public Health, University of Sydney, 2004."This treatise is submitted in partial satisfaction of the requirements for the Degree of Master of International Public Health (Hons), University of Sydney". Bibliography: leaves 10-15.
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Ahlgren, Johan. "Studies on Prediction of Axillary Lymph Node Status in Invasive Breast Cancer." Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis : Univ.-bibl. [distributör], 2002. http://publications.uu.se/theses/91-554-5221-3/.
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Johnson, Laura. "Magnetic nanoparticles for sentinel lymph node imaging and biopsy in breast cancer." Thesis, King's College London (University of London), 2012. https://kclpure.kcl.ac.uk/portal/en/theses/magnetic-nanoparticles-for-sentinel-lymph-node-imaging-and-biopsy-in-breast-cancer(978692de-a495-4df1-ac0f-303227bed0dd).html.
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Background Axillary nodal status is the single most important prognostic factor in breast cancer diagnosis. If cancerous cells are present, the sentinel lymph node (SLN) is the axillary lymph node that is most likely to contain metastatic disease. In early stage breast cancer, the SLN is localised (then surgically removed for pathological analysis) using a radioisotope and/or a blue dye injected into the breast Super-paramagnetic iron oxide (SPIO) nanoparticles are novel agents that, when injected, could potentially both localise and characterise the SLN using MRI such that surgical SLN biopsy is no longer required. Aims To evaluate axillary SLN localisation after SPIO injection with, pre-operatively, axillary MRI and, intra-operatively, with a hand held magnetometer and to characterise SLN SPIO uptake using ex-vivo MRI. Methods From November 2009 - March 2011, 51 patients with early stage breast cancer underwent SLN biopsy following a subcutaneous injection of SPIO in addition to the standard injection of radioisotope (Tc99M) and blue dye. SPIO injection technique was refined during the trial with an initial dose of 2mls and then 4mls in 8 and then 43 women respectively. Pre-operative axillary in vivo MRI (1.5T) was carried out on 14 women and ex vivo high resolution MRI (9.4T) on 36 nodes. During surgery, an SLN was defined as either "hot", "blue", "palpable" or "SPIO detected". Axillary clearance was carried out for SLN-positive disease. Results In total, 11 of the 51 patients had positive SLNs. On pre-operative axillary MRI, SPIO uptake was noted in at least one node in all 14 patients. A total of 35 nodes were identified. Uptake of SPIO in the SLN was seen at a minimum of 12mins post injection. Involved SLNs were not differentiated from normal SLNs following morphological characterisation or based on loss of T2 signal within the individual SLN. At SLN biopsy, 134 hot, blue, palpable or SPIO-containing nodes were identified in 51 patients. The magnometer identified 92 SPIO-containing nodes in 51 (84%) patients. One node in one patient was not identified using the combined technique but was found to contain SPIO. Of the 16 hot, blue or palpable involved nodes in 11 patients, 9 contained SPIO. In summary, the SPIO SLN localisation rate and FNR in patients was 84% and 16% respectively. Ex vivo SLN MRI demonstrated SPIO uptake in all 35 SLNs preferential to the sinuses and sub-capsular spaces. Of the 3 involved nodes, areas of metastasis did not take up SPIO, whereas in normal areas of the node, SPIO was positively identified. Conclusion In our study, subcutaneous SPIO, a novel SLN-localising agent, was taken up by axillary nodes and identified on pre-operative axillary MRI. Node positive SLNs were identified on ex vivo MRI, but SPIO did not demonstrate sufficient accuracy at SLN localisation for routine clinical use.
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Bhattarai, Nihit. "Differentiation Mechanisms of Myeloid-Lymphatic Progenitors that Promote Lymph Node Metastasis in Breast Cancer." OpenSIUC, 2020. https://opensiuc.lib.siu.edu/theses/2657.
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Metastasis to distant organs, a major cause of mortality from cancer, is often preceded by tumor spread to regional lymph nodes (LN). This process is supported exclusively by lymphatic vessels within or around the tumor. It is important to understand the mechanism by which tumors induce generation of new lymphatic vessels because interference with this early stage of tumor spread might prevent distant metastasis. Tumor lymphatic formation is thought to be induced by VEGF-C factor that activates its receptor VEGFR-3 expressed in lymphatic endothelial cells (LEC). However, this process also requires participation of tumor-recruited Myeloid-Lymphatic Endothelial Cell Progenitors (M-LECPs). We recently showed that M-LECPs are abundant in mouse and human breast tumors and that their density strongly correlates with both lymphatic formation and nodal metastasis. Here, we show that M-LECPs derived from bone marrow (BM) myeloid precursors can be differentiated in vitro by pretreatment with colony stimulating factor-1 (CSF-1) followed by activation of Toll-like Receptor-4 (TLR4) applied in this but not in a reverse order. We also identified CSF-1 as the best inducer of M-LECP differentiation out of 16 screened cytokines. Based on flow cytometry analysis of LEC- and myeloid-specific markers, CSF-1R-positive cells yielded significantly higher number of myeloid-lymphatic endothelial progenitors than BM cells lacking this receptor. Consistently, both anti-CSF-1R antibody and BLZ945 drug significantly reduced the number of myeloid-lymphatic progenitors compared with untreated controls. We also found that the requirement for CSF-1 to precede activation of TLR4 pathway is likely routed in CSF-1 dependent upregulation of essential components of TLR4 ligand recognition complex such as MD2, CD14, CD11b and CD18. In conclusion, we show that mouse BM cells can be differentiated into lymphatic endothelial progenitors by treatment with CSF-1 and TLR4 ligand, LPS. We also show that treatment with CSF-1 has to precede activation of TLR4 pathway as upregulation of several components of the TLR4 pathway is required for optimal M-LECP differentiation. To our knowledge, this is the first evidence identifying specific factors and sequence of their exposure that drive the formation of the lymphatic endothelial lineage from early myeloid precursors.
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Owusu, Miriam Sekyere. "Lymphedema, post breast cancer treatment at Komfo Anokye Teaching Hospital, Kumasi, Ghana." Thesis, Cape Peninsula University of Technology, 2011. http://hdl.handle.net/20.500.11838/2262.
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Thesis (MTech (Nursing))--Cape Peninsula University of Technology, 2011.To determine the incidence, risk factors and the treatment of lymphedema after breast cancer treatment at the oncology unit of KATH, Kumasi, Ghana from 01 January 2005 to 31 December 2008. Descriptive retrospective survey was used. Using a data capture sheet, data was collected from the medical records of the breast cancer patients. Breast cancer and lymphedema-related variables were collected. Data was analyzed as descriptive statistics. Chi-square test was applied to determine whether or not two variables are independent variables. Among 313 patients treated for breast cancer between 2005 and 2008, 31 (9.9%) developed lymphedema after treatment. A chi-square test showed that axillary lymph node dissection was statistically a significant risk factor of lymphedema (Chi-square test value=7.055, P value=0.008). Radiation and late stage of breast cancer diagnosis may have contributed in development of lymphedema despite having P value> 0.05. Age, body mass index (BMI) and hypertension were also not associated with lymphedema.
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de, Boniface Jana. "Sentinel Node Biopsy in Breast Cancer : Clinical and Immunological Aspects." Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis : Univ.-bibl. [distributör], 2007. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-7890.
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Vasques, Paulo Henrique DiÃgenes. "Comparison between hemosiderin and technetium-99 in the identification of sentinel lymph node in breast cancer." Universidade Federal do CearÃ, 2016. http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=16007.
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CoordenaÃÃo de AperfeÃoamento de Pessoal de NÃvel SuperiorIntroduction and objective: Sentinel Lymph Node Biopsy (SLNB) has currently replaced axillary dissection in early-stage breast cancer in clinically tumor-free patients. Technetium-99 (99Tc) is the gold standard for the identification of Breast Sentinel Lymph Node (SLN). Blue dyes are a less expensive and widely used option in Brazil. These dyes are responsible for several adverse and hypersensitivity reactions that â although rare â can put patientsâ lives at risk. There is an interest in the discovery of new equivalent substances with less side effects than those used in SLNB. This research assesses the safety and equivalence of the use of hemosiderin in SLNB in breast cancer compared to technetium-99 (99Tc). Hemosiderin is a hemoglobin derivate identified in a preclinical trial that has proven to be effective in the SLNB of female dogsâ breasts. The aim of this research is to assess the safety and potential equivalence of the use of hemosiderin in SLNB in human breast compared to the 99Tc. Method: The experiments took place in the period from September 2011 to September 2013. Patients were selected from the Mastology Service of the MEAC/HC/UFC and included 14 volunteer women with breast cancer with primary tumors (T1/T2) and clinically tumor-free axilla who were submitted to SLNB using hemosiderin, produced based on an aseptic hemolysate obtained from autologous blood, injected in the periareolar region 24h before surgery on an outpatient basis. 0.5 mCi of 99Tc was also injected in the subareolar region in the immediate preoperative period. Patients underwent breast MRI and mammary scintigraphy. In the operating room, patients â under general anesthesia â were submitted to SLNB, with incision in the axillary fold guided by Gamma-Probe and dissection by planes until the identification of the point of maximum uptake of 99Tc, identifying the marked sentinel lymph nodes (SLN) and their colors. Breast procedure was defined based on the correlation of the size and location of primary tumor and the axilla procedure was performed based on the presence or not of SLN metastasis. All surgical specimens were sent for pathological and immunohistochemical study. Results: There were no side effects, allergic reactions, surgical infection or toxicity related to the method applied. The conocordance rate between hemosiderin and 99Tc was 100%. The sensitivity and accuracy of hemosiderin was 100%. An incidental finding refers to magnetic properties of axillary lymph nodes (ALN) identified as an hypersignal in the NMR with hemosiderin in 100% of the exams. In two of four cases with positive SLN on histopathology, the image of the NMR with hemosiderin suggested neoplastic involvement of the marked lymph node. Conclusion: Hemosiderin proved to be an efficient and safe dye that is equivalent to 99Tc in breast SLNB.
IntroduÃÃo e objetivo: Atualmente, a Biopsia do Linfonodo Sentinela (BLS) substitui o esvaziamento axilar no estadiamento do cÃncer de mama inicial com axila clinicamente negativa. O tecnÃcio 99 (Tc99) à o padrÃo ouro para identificaÃÃo do Linfonodo Sentinela (LS) da mama. Os corantes azuis sÃo uma opÃÃo menos onerosa e mais difundida no Brasil. Estes corantes sÃo responsÃveis pelas reaÃÃes adversas e de hipersensibilidade que, embora raras, podem pÃr em risco à vida dos pacientes. Hà interesse na descoberta de novas substÃncias equivalentes e com menores efeitos colaterais Ãs usadas na BLS. Aqui se avaliam a seguranÃa e a equivalÃncia do uso da hemossiderina, em comparaÃÃo ao tecnÃcio 99 (Tc99) na BLS no cÃncer de mama. A hemossiderina à um derivado da hemoglobina, identificada em estudo prÃ-clÃnico, que se mostrou eficaz na BLS da mama da cadela. O objetivo desta pesquisa à avaliar a seguranÃa e a potencial equivalÃncia do uso da hemossiderina em comparaÃÃo com o Tc99 na BLS da mama humana. MÃtodo: Os experimentos ocorreram no perÃodo de setembro de 2011 a setembro de 2013. As pacientes selecionadas no ServiÃo de Mastologia da MEAC/HC/UFC, foram 14 mulheres, voluntÃrias, portadoras de cÃncer de mama, com tumores iniciais (T1/T2) e axila clinicamente negativa, que se submeteram a BLS, utilizando hemossiderina, produzida com base em um hemolisado, assÃptico, obtido de sangue autÃlogo, injetada na regiÃo subareolar, ambulatorialmente, 24h antes da cirurgia. No prÃ-operatorio imediato, injetou-se, tambÃm, na regiÃo subareolar, 0,5mci de Tc99. As pacientes foram submetidas a ressonÃncia magnÃtica das mamas, e a cintilografia mamÃria. No Centro CirÃrgico, as pacientes sob anestesia geral realizaram a BLS com incisÃo na prega axilar, guiada pelo gamma-probe, dissecÃÃo por planos atà a identificaÃÃo de ponto de captaÃÃo mÃxima do Tc99, identificando-se o Linfonodo Sentinela (LS) marcado e a sua coloraÃÃo. O procedimento da mama foi definido em correlaÃÃo com o tamanho e localizaÃÃo do tumor primÃrio e a conduta em relaÃÃo à axila em funÃÃo da presenÃa ou ausÃncia de metÃstase no LS. Toda peÃa cirÃrgica foi encaminhada à avaliaÃÃo anatomopatolÃgica e imunohistoquÃmica. Resultados: NÃo foram observados efeitos colaterais, reaÃÃes alÃrgicas, infecÃÃo cirÃrgica ou toxicidade relacionados ao mÃtodo empregado. A taxa de concordÃncia entre a hemosiderina e o Tc99 foi de 100%. A sensibilidade e acurÃcia da hemossiderina foi 100%. Um achado incidental foi o magnetismo dos linfonodos axilares (LA) identificados como hipersinal à RNM com hemossiderina em 100% dos exames. Em dois de quatro casos de LS positivos na histopatologia, a imagem da RNM com hemossiderina sugeria comprometimento neoplÃsico do linfonodo marcado. ConclusÃo: A hemossiderina se mostrou um corante eficiente, seguro e equivalente ao TecnÃcio 99 na BLS da mama
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Celebioglu, Fuat. "Sentinel node biopsy in breast cancer : aspects on validation, diagnostics and lymphatic drainage pattern /." Stockholm, 2006. http://diss.kib.ki.se/2006/91-7140-772-3/.
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Greene, Carmen M. "Experience using a small field of view gamma camera for intraoperative sentinel lymph node procedures." Thesis, Available online, Georgia Institute of Technology, 2006, 2006. http://etd.gatech.edu/theses/available/etd-01132006-160335/.
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Kano, Masato. "Detection of Lymph Node Metasatasis of Oesophageal Cancer by RT-nested PCR for SCC antigen mRNA." Kyoto University, 2001. http://hdl.handle.net/2433/150176.
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Griggs, Caitlin Elizabeth. "Generation of myeloid-derived lymphatic endothelial cell progenitors (M-LECPs) by TLR4-mediated inflammation and de novo VEGFR-3 signaling in breast cancer." OpenSIUC, 2016. https://opensiuc.lib.siu.edu/theses/1902.
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Breast cancer is the second leading cause of cancer-related death in women in the United States. Complications that lead to mortality of cancer patients are associated with tumor metastasis. Specifically, lymphatic metastasis in breast cancer patients strongly correlates with poor patient survival and this process is facilitated by the formation of new tumor lymphatic vessels termed lymphangiogenesis. Previously, our lab reported that lymphangiogenesis was promoted by a distinct subset of bone marrow (BM)-derived myeloid cells that co-express lymphatic-specific markers designated as myeloid-derived endothelial cell progenitors (M-LECPs). Furthermore, our lab has generated M-LECP in vitro from a mouse macrophage cell line (RAW264.7) by LPS stimulation. Taken together, these data suggest that chronically inflamed sites drive M-LECP differentiation and that these cells can contribute to the formation of new lymphatic vessels and promote lymph node metastasis. Evidence supporting this hypothesis was indicated by high levels of circulating M-LECP in peripheral blood of breast cancer patients but undetectable levels in healthy donors, cancer-free donors. Additionally, the generation of M-LECP was prompted through TLR4-signaling pathway, and de novo expression of VEGFR-3 and VEGF-C. This co-expression produces an autocrine loop essential for pro-lymphatic reprogramming in both primary human monocytes and the immature monocytic cell line, THP-1. Taken together, these data indicate the major regulatory role of TLR4 in inflammation-driven lymphangiogenesis involves the recruitment and differentiation of M-LECP, a process that may promote lymphatic metastasis.
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Jafer, Fatema. "THE CLINICAL VALUE OF SPECT/ CT IN IDENTIFYINGSENTINEL LYMPH NODES IN PATIENTS WITH BREASTCANCER: A SYSTEMATIC REVIEW." Thesis, Örebro universitet, Institutionen för medicinska vetenskaper, 2021. http://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-94687.
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Introduction: Sentinel lymph node biopsy is an established method used to investigate the riskof lymphatic metastasis especially in breast cancer and melanoma patients. SPECT/ CT isconsidered to be an advantageous method in mapping of sentinel nodes. Aim: The aim of this systematic literature review was to investigate the clinical value ofSPECT/ CT in the detection of sentinel lymph nodes in breast cancer patients. Method: Using specific search terms the database PubMed was used to find studies of potentialrelevance for this systematic review. Criteria for inclusions and exclusion were decided todetermine article relevance. Eligibility of articles was determined according to these criteriawhich lead to the selection of the specific articles included in this study. Results: Eleven studies were included in this systematic review. Seven out of 8 studies foundhigher identification rates of sentinel lymph nodes with SPECT/ CT in comparison to planarlymphoscintigraphy. SPECT/ CT could detect additional lymph nodes in 9 out of 9 studies.SPECT/ CT detected additional extra-axillary lymph nodes in 6 out of 7 studies. SPECT/ CTdetected lymph nodes in 9 out of 9 studies where planar lymphoscintigraphy was negative.Information from additional SPECT/ CT lead to changes in surgical treatment plan in 4 out of4 studies. None of the included studies contained information about change in oncologicaltreatment plan due to findings on SPECT/ CT. Conclusion: SPECT/ CT is an imaging technique with much potential as it seems to allow amore accurate SLN mapping and more precise anatomical localization of SLN in breast cancerpatients, specifically in certain clinical situations. Despite this however, the impact of SLNmapping through SPECT/ CT on patient prognosis remains uncertain.
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Takada, Masahiro. "Prediction of axillary lymph node metastasis and the pathological response to neoadjuvant chemotherapy in patients with primary breast cancer using a decision tree-based model." Kyoto University, 2012. http://hdl.handle.net/2433/160969.
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Matheus, Carolina Nascimben 1980. "Avaliação do fluxo sanguíneo do membro superior de mulheres submetidas a abordagem axilar para tratamento do câncer de mama : Blood flow in the superior limbs of women with breast cancer undergoing a surgical approach to the axilla." [s.n.], 2015. http://repositorio.unicamp.br/jspui/handle/REPOSIP/312844.
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Orientador: Luís Otávio Zanatta SarianTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
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Resumo: Objetivo: Esta tese visou avaliar os parâmetros vasculares arteriais e venosos dos vasos axilares e braquiais em mulheres submetidas a tratamento para câncer de mama. Subdividimos estas avaliações conforme os objetivos abordados em duas publicações, respectivamente: 1) Comparar aos parâmetros de circulação venosa e arterial nos vasos axilares e braquiais em função do tipo de abordagem cirúrgica da axila (BLS ou LAT) em até seis meses após a intervenção. 2) Identificar os fatores que influenciam os parâmetros vasculares da veias axilares e braquiais ipsilaterais à cirurgia para tratamento do câncer de mama. Métodos: Foram identificadas 547 pacientes consecutivas, submetidas a tratamento cirúrgico para câncer de mama entre agosto de 2012 e janeiro de 2014. Depois de seguir critérios de inclusão e exclusão, 197 mulheres foram recrutadas. O projeto foi aprovado pelo comitê de ética do hospital e todos os pacientes assinaram o termo de consentimento informado. Os critérios de inclusão foram 1) câncer da mama primário operável 2) abordagem axilar cirúrgica; 3) não ter sido submetida a reconstrução da mama. Os critérios de exclusão foram 1) câncer de mama bilateral, 2) história prévia de procedimentos cirúrgicos para um dos membros superiores ou no tórax, 3) comprometimento ortopédico ou neurológico de um dos membros superiores, 4) insuficiência renal ou cardíaca. Todas as pacientes responderam a um breve questionário sobre suas características clínicas e epidemiológicas. Foi então realizada avaliação ultrassonográfica dos vasos braquiais e axilares, bilateralmente, nos seguintes momentos: no dia anterior à cirurgia e 1, 3, 6 e 12 meses após a cirurgia. No primeiro artigo, comparamos os parâmetros arteriais e venosos, até seis meses após a cirurgia, em função da realização de dissecção linfática completa ou linfonodo sentinela; no segundo, restringimos as análises ao sistema venoso e estendemos a avaliação para até 1 ano após a cirurgia, comparando os parâmetros vasculares em função de características clínicas e epidemiológicas das pacientes e das modalidades de tratamentos utilizados. Resultados: Foram encontradas restrições de diâmetro em veias do braço ipsilateral ao câncer de mama de mulheres submetidas à dissecção axilar (LAT), efeito que não foi observado no grupo BLS. A área da secção transversal de veias braquial e axilar diminuiu progressivamente até seis meses, com a redução do fluxo sanguíneo concomitante destes vasos. Encontramos, na mulher sem linfedema, que a área de secção transversal e fluxo venoso do sangue (especialmente veia braquial) são negativamente afetados pela cirurgia e / ou quimioterapia / radioterapia. Este efeito prejudicial parece persistir até um ano. Não houve diferença significativa em nenhum dos parâmetros estudados entre os vasos ipsi e contralaterais ao câncer de mama. Conclusões: De maneira geral, nosso estudo demonstra que os tratamentos cirúrgicos, especialmente LAT, e a radio e quimioterapia, possuem efeitos deletérios sobre a circulação sanguínea dos vasos axilares e braquiais, sobretudo venosos. Esses efeitos são aparentemente permanentes e há necessidade de extensão do tempo de follow-up a fim de avaliar se o desenvolvimento subsequente de linfedema ocorrerá em associação às alterações vasculares
Abstract: Objective: The aim of this thesis was to evaluate the arterial and venous vascular parameters of the axillary and brachial vessels in women who underwent treatment for breast cancer. We subdivided these assessments according to the following objectives, in two publications: 1) To compare the venous and arterial vascular parameters in the axillary vessels and brachial depending on the type of axillary surgical approach (SLNB or ALND) within six months after the intervention. 2) To identify which factors influence the vascular parameters of axillary and brachial veins ipsilateral to surgical for treatment of breast cancer. Methods: We identified 547 consecutive patients undergoing surgical treatment for breast cancer between August 2012 and January 2014. After following inclusion and exclusion criteria, 197 women were recruited. The project was approved by the hospital's ethics committee and all patients signed an informed consent form. Inclusion criteria were 1) primary operable breast cancer 2) surgical axillary approach; 3) not having undergone breast reconstruction. Exclusion criteria were 1) bilateral breast cancer, 2) history of previous surgical procedures for one of the upper limbs or breast, 3) orthopedic or neurological impairment of one upper limb, 4) kidney or heart failure. All patients completed a brief questionnaire about their clinical and epidemiological characteristics. Then we performed Doppler ultrasonography evaluation of axillary and brachial vessels, bilaterally, at the following times: the day before surgery and 1, 3, 6 and 12 months after surgery. In the first article, we compared the arterial and venous parameters, up to six months after surgery, depending on SLNB or ALND; in the second, we restricted the analysis to the venous system and extend the evaluation for up to 1 year after surgery, comparing the vascular parameters with clinical and epidemiological characteristics of patients and treatment modalities used. Results: diameter restrictions were found in the ipsilateral veins of the arm in women with breast cancer undergoing ALND, and that effect was not observed in SLNB group. The cross sectional area of brachial and axillary veins progressively decreased up to six months, with concomitant reduction of blood flow to these vessels. In women with no lymphedema, the cross-sectional area and venous blood flow (especially brachial vein) are negatively affected by surgery and / or chemotherapy / radiotherapy. This detrimental effect seems to persist up to one year. There was no significant difference on studied parameters between ipsilateral and contralateral vessels to breast cancer. Conclusions: In essence, our study shows that surgical treatments, especially ALND, and the radiation and chemotherapy, have deleterious effects on blood circulation of the axillary and brachial vessels, especially venous. These effects are apparently permanent, prompting the extension of the follow-up evaluation in order to assess whether subsequent lymphedema formation will be associated with vascular abnormalities
Doutorado
Oncologia Ginecológica e Mamária
Doutora em Ciências da Saúde
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Alvarenga, César Augusto 1975. "Tipos especiais histológicos de carcinomas da mama = perfil imunoistoquímico com ênfase na classificação molecular." [s.n.], 2011. http://repositorio.unicamp.br/jspui/handle/REPOSIP/310564.
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Orientadores: Luiz Carlos Zeferino, Fernando Carlos de Landér SchmittTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
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Resumo: A maioria dos carcinomas invasivos da mama são classificados como carcinoma ductal invasivo, sem outras especificações (CDI-SOE), enquanto que cerca de 25% são definidos como tipos especiais histológicos (TEH). Esses TEH de carcinomas da mama são categorizados em pelo menos 17 entidades patológicas distintas. Como a maioria dos estudos realizados na literatura em relação à classificação molecular (luminais A e B, sobre expressão de HER2, "basal-like") tenham utilizado somente CDI-SOE e lobulares invasivos, um estudo com mais TEH seria necessário. A CK19 pode ser utilizada como método de avaliação do linfonodo sentinela através de uma técnica molecular chamada de OSNA (amplificação de ácido nucléico de um passo). A expressão de sua positividade foi avaliada somente nos carcinomas ductais, lobulares, medulares e de pequenas células. Realizado tissue microarray (TMA) no IPATIMUP (Porto-Portugal) de 157 casos selecionados dos arquivos do Instituto de Patologia de Campinas. Obtido um total de 121 e 116 casos no TMA do perfil molecular e da CK19, respectivamente, estes incluíram carcinomas tubulares, mucinosos, papilares encapsulados e invasivo, lobulares, micropapilares, medulares, metaplásicos, apócrinos e mistos. Foram utilizados marcadores imunoistoquímicos tais como: RE, RP, RA (somente nos apócrinos), HER2, Ki67, P-caderina, CK5, EGFR e p63 para classificá-los quanto à classificação molecular e CK19 para avaliar sua expressão na mama antes da realização da técnica de OSNA em linfonodo sentinela. Tubulares, papilares e mucinosos foram todos luminais A e B, dado semelhante ao perfil de expressão genética; medulares e metaplásicos foram quase todos "basais-like" (76.2% e 90%, respectivamente), enquanto que ao nível transcriptômico, todos os casos pertencem ao subtipo "basallike"; micropapilares foram luminais A e B e sobre-expressão de HER2, sendo que ao nível transcriptômico são praticamente todos luminais B devido à alta expressão de HER2; apócrinos foram os mais heterogêneos de todos com casos luminais A e B, sobre-expressão de HER2 e "basais-like", dado diferente ao nível transcriptômico que revela o subtipo "molecular apócrino" (RE-/RA+/HER2- ou +). O risco relativo do Ki67 aumentou entre os TEH, sendo que o carcinoma medular teve 110 vezes mais risco de aumento do Ki-67 em relação ao tubular. A CK19 foi expressa em 98.2% dos TEH de carcinomas da mama, dado idêntico ao estudo anterior de Chu et al, sendo que sua positividade aumentou nos casos em que o bloco de parafina foi inteiramente estudado, pois sua marcação foi focal em muitos casos avaliados no TMA. Isso pode produzir eventualmente resultados falso-negativos nas "corebiopsies"
Abstract: Most invasive breast carcinomas are classified as invasive ductal carcinoma, not otherwise specified (IDC-NOS), while approximately 25% are defined as special histological types (HST). These HST of breast carcinomas are categorized into at least 17 distinct pathological entities. Most studies in the literature regarding the molecular classification (luminal A and B, HER2- overexpression, "basal-like") were evaluated only in IDC-NOS and in lobular invasive carcinoma, a study with more HST of breast carcinoma would be necessary. The CK19 can be used as a method of evaluation of sentinel lymph node using a molecular technique called OSNA (one step acid nucleic amplification). The expression of CK19 positivity was assessed only in ductal, lobular, medullary and small cell carcinomas. It was performed tissue microarray (TMA) in IPATIMUP (Porto-Portugal) of 157 cases selected from the archives of the Instituto de Patologia de Campinas, a private laboratory. A total of 121 and 116 TMA cases in the molecular profiling and in the CK19 studies was obtained, respectively, including tubular, mucinous, papillary encapsulated and invasive, lobular, micropapillary, medullary, metaplastic, apocrine and mixed carcinomas. It was used immunohistochemical markers such as ER, PR, RA (only in apocrine carcinomas), HER2, Ki67, P-cadherin, CK5, EGFR and p63 to classify them as the molecular classification and as the CK19 expression in the breast before performing the technique of OSNA in sentinel lymph node. Tubular, papillary and mucinous were all luminal A and B, as similar as the geneexpression profiling; medullary and metaplastic were almost all "basal-like" (76.2% and 90%, respectively), while at transcriptome level, all cases belong to subtype "basal-like"; micropapillary was luminal A and B and HER2- overexpression and in the transcriptomic level was virtually all luminal B due to high expression of HER2; apocrine was the most heterogeneous tumours of our study with luminal A and B, HER2-overexpression and "basal-like" cases. This data was different from transcriptomic level that revealed the "molecular apocrine" subtype (RE-/ RA+/ HER2- or +). The relative risk of Ki67 increased between HST, because medullary carcinomas had 110 times more risk of increased Ki-67 than tubular carcinomas. The CK19 was expressed in 98.2% of HST of breast carcinomas, data identical to the Chu et al study, and the positivity increased in cases where the entire paraffin block had been fully studied, because its labeling was focal in many cases evaluated on TMA. This CK19 focal expression can produce false-negative results in the breasts "corebiopsies"
Doutorado
Oncologia Ginecológica e Mamária
Doutor em Ciências da Saúde
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Delazeri, Gerson Jacob. "Injeção intraoperatória de dextran-500-99m tecnécio para identificação do linfonodo sentinela em câncer de mama." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2010. http://hdl.handle.net/10183/25113.
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Objetivos: Avaliar a eficácia da injeção intraoperatória para identificação do linfonodo sentinela (LS) em câncer de mama com o uso do Dextran 500-99m-Tecnécio (Tc) e azul patente. Analisar se as doses do radiofármaco, o IMC (índice de massa corporal) e o volume da mama influenciam no tempo para migração ao LS. Metodologia: Estudo prospectivo, realizado entre abril de 2008 e junho de 2009, que incluiu 74 biópsias de LS em pacientes com câncer de mama em estádios T1N0 e T2N0. Injetou-se, após indução anestésica, de 0,5 a 1,5 mCi de Dextran 500-99m-Tc filtrado 0,22 μm na região subareolar num volume de 5 ml e 2 ml de azul patente. Resultados: Identificou-se o LS em 100% dos casos. Um LS (1,35%) estava marcado apenas com o azul patente. A taxa de identificação com o “probe” foi de 98% (73/74 casos). A dose média de radiofármaco aplicada foi 0,97 mCi + 0,22. O tempo médio para marcação do LS foi de 10,7 minutos (+ 5,7min). Identificamos em média 1,66 LS com o radioisótopo. A dose aplicada não apresentou relação com o tempo para captação (p=0,73). Quanto maior o volume da mama e IMC, maior o tempo para captação na região axilar (Pearson Correlation r=0,393 p<0,01; r=0,469 p<0,01 - respectivamente). Conclusão: A injeção intraoperatória do radiofármaco é eficaz para identificação do LS em câncer de mama. O tempo para marcação do LS é maior em pacientes com IMC elevado e mamas volumosas. Doses maiores de radiofármaco não diminuem o tempo de migração.Objectives: To determine the identification of sentinel lymph node (SLN) in breast cancer after intraoperative injection of Dextran 500‐99mTechnetium (Tc) and blue dye. To analyze if the doses of the radioisotope, body mass index (BMI) and breast volume influence the migration time of the SLN. Methodology: Prospective study between april 2008 and june 2009, which included 74 biopsies of SLN in patients with breast cancer in stages T1N0 and T2N0. Intraoperative injection after induction of general anesthesia, 0.5 to 1.5 mCi of dextran 500‐99m‐Tc filtered 0.22 μm in the subareolar region in a volume of 5 ml and 2 ml of blue dye. Results: We identified the SLN in 100% of cases. In one case (1.35%) the SLN was marked only with the blue dye. The SLN identification rate with the probe was 98% (73/74 cases). The mean dose of radioisotope injected was 0.97 + 0.22 mCi. The average time to mark the SLN was 10.7 minutes (+ 5.7 min). We identified an average 1.66 SLN with the radioisotope. The dose had no effect on the time to capture (p = 0.73). The larger breast volume and BMI, the greater the capture time in the axillary region (Pearson Correlation r=0.393 p <0.01, r=0.469 p <0.01 - respectively). Conclusion: Intraoperative injection of the radioisotope is effective for the identification the SLN in breast cancer. Time to mark the SLN is higher in patients with high BMI and large breasts. Higher doses of radioisotope do not decrease the migration time.
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Fontana, Vivian. "Extensão do comprometimento axilar após biópsia de linfonodo sentinela positivo nas pacientes com câncer de mama operadas no Hospital de Clínicas de Porto Alegre." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2017. http://hdl.handle.net/10183/164317.
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Introdução: o status dos linfonodos axilares permanece um dos mais importantes fatores prognósticos no carcinoma de mama em estágios iniciais, além de definir o uso de terapias complementares. A biópsia de linfonodo sentinela (BLNS) surgiu com a finalidade de estadiar a axila com o mínimo de morbidade, tendo como objetivo a identificação e o estudo patológico do primeiro linfonodo axilar proveniente da drenagem linfática da mama. Pacientes com axila clinicamente negativa têm indicação de biópsia de linfonodo sentinela como método de estadiamento da axila, e quando o resultado era positivo para metástase recomendava-se o esvaziamento axilar. Por recomendação do ACOSOG Z0011, o esvaziamento axilar (EA) após uma biópsia de linfonodo sentinela positivo não é necessário. Esse estudo demonstrou não haver benefício em realizar o EA na presença de LNS positivo na sobrevida global ou na sobrevida livre de doença. Objetivos: Avaliar a taxa de recidiva e morte em pacientes submetidas à cirurgia conservadora de mama e BLNS positiva com posterior esvaziamento axilar no Hospital de Clínicas de Porto Alegre; e, como objetivo secundário, avaliar as características clínicas e patológicas dessa população. Método: foi realizado um estudo de coorte retrospectiva, incluindo pacientes com diagnóstico de carcinoma de mama invasor submetidas à cirurgia conservadora da mama e BLNS, cujo resultado foi positivo para presença de metástases, e foram submetidas ao EA o período de janeiro de 2004 a dezembro de 2008. Resultados: foram incluídas 144 pacientes submetidas à biópsia de linfonodo sentinela e CCM; 33 tiveram o achado de biópsia de linfonodo sentinela positivo para metástase, e dessas 33 pacientes restaram 27 para análise dos dados. A taxa de sucesso na identificação do LNS foi de 0,96. A idade média das pacientes foi de 53,8 anos, o número de LNS ressecados foi de 1,6 por paciente; a média do tamanho tumoral foi de 2,3 cm. Seis pacientes apresentaram doença axilar residual correspondendo a 22,2% da amostra e tiveram um risco relativo de morte de 3 vezes mais para aquelas sem doença axilar residual e 50% a mais de desenvolvimento de metástases. Conclusão: O comprometimento axilar é importante fator no prognóstico das pacientes com câncer de mama, quanto maior o comprometimento da axilar pior será o desfecho de sobrevida livre de doença e de morte. Acreditamos que se pode aplicar a conduta do ACOSOG Z0011 também nas pacientes do HCPA devido à alta sensibilidade do método no nosso meio.Introduction: The status of axillary lymph nodes remains one of the most important prognostic factors in breast carcinoma in the early stages, in addition it helps to defining the use of complementary therapies. Sentinel lymph node biopsy (SLNB) was developed with the purpose of staging the axilla with minimal morbidity, aiming at the identification and pathological study of the first axillary lymph node from the lymphatic drainage of the breast. Patients with clinically negative lymph node have indication of SLNB as a method of axillary staging, and with a positive finde for metastasis the axilar clereance was performed. Nowadays, due to the ACOSOG Z0011 Study, the axillary dissection (AD) after a positive SLNB for metastasis was put in check. This estudy have as a result no difference in global survive ou disease free survive if ALND was not performed in a positive SLNB. In the present study, we intend to evaluate the clinical and histopathological characteristics of patients submitted to breast conservative surgery and sentinel lymph node biopsy with a positive result for metastasis. Main objective: Evaluate the rate of recurrence and death in patients submitted to conservative breast surgery and BLNS with posterior axillary emptying at Hospital de Clínicas, Porto Alegre. It is a secondary objective to evaluate the clinical and pathological characteristics of this population. Material and Methods: A retrospective cohort study was performed, including 144 patients diagnosed with invasive breast carcinoma submitted to conservative breast surgery and SLNB, whose results were positive for metastases, and were submitted to AD, at the Mastology Unit of the Hospital de Clinicas de Porto Alegre (HCPA), from January 2004 to December 2008. Results: Of 144 patients submitted to SLNB and BCS, 33 had SLNB positive for metastasis, of these 33 patients remained 27 for data analysis. The success rate in LNS identification was 0.96. The mean age of the patients was 53.8 years, the number of resected SLN was 1.6 per patient; The mean tumor size was 2.3 cm. Six patients had residual axillary disease corresponding to 22.2% of the sample and had a relative risk of death of 3 times more for those without residual axillary disease and 50% more for the development of metastases. Conclusion: Axillary involvement is an important factor in the prognosis of patients with breast cancer, and the greater the axillary impairment, the worse the diseasefree survival outcome and death. We believe that the ACOSOG Z0011 trial can also be applied to HCPA patients who meet the inclusion criteria for this purpose, due to the high sensitivity of the method in our environment.
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Bernardes, Franciele Cristina. "Caracterização dos padrões de drenagem linfática nas linfocintilografias de pacientes com câncer de mama." Universidade de São Paulo, 2012. http://www.teses.usp.br/teses/disponiveis/82/82131/tde-17072012-085250/.
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O câncer de mama (CA de mama), com exceção do câncer de pele do tipo não melanoma, é o tumor de maior incidência dentre as mulheres, sendo que no Brasil são encontrados principalmente nas regiões Sul e Sudeste. Seu principal tratamento é o cirúrgico. A disseminação do tumor pode ocorrer por via linfática, acometendo linfonodos regionais. A biópsia do linfonodo sentinela (BLNS) é um procedimento altamente relevante, é altamente sensível na identificação de metástases. A técnica de linfocintilografia (LINCT) pré-operatória é essencial, pois permite avaliar a cadeia linfática acometida e possibilita a visualização do linfonodo sentinela (LNS) durante a cirurgia. O objetivo é descrever os padrões de drenagem linfática e avaliar a contribuição da LCINT na localização dos LNS em pacientes com CA de mama. No período de março de 2009 a agosto de 2011 foram estudados 70 casos sequenciais da rotina clínica, submetidos ao tratamento cirúrgico do CA de mama com estudo do LNS através da técnica de LCINT. Na LCINT foram aplicadas 4 injeções intradérmicas contendo 37 MBq (1,0 mCi) do FITATO-Tecnécio99m, ao redor da aréola mamária. Após a localização do LNS foi realizado marcações na pele, nas incidências anterior, oblíqua e lateral, para auxiliar o cirurgião na abordagem cirúrgica ulterior, juntamente com a sonda gama intra-operatória e corante azul patente. Dos 70 casos submetidos ao estudo, todos são do sexo feminino (100%) com faixa etária entre 28 e 77 anos, média de 54 anos. O tamanho médio do tumor encontrado nos pacientes foi de 1,4 cm. Os tipos histológicos mais incidentes foram o carcinoma ductal invasivo com 45 (64,4%) pacientes, seguido de carcinoma ductal in situ com 16 (22,8%). No exame de LCINT, todos os pacientes apresentaram drenagem linfática do radiofármaco a partir do local da injeção. Em 43 (61.5%) pacientes, observamos drenagem para 1 LNS, em 21 (30%) para 2 LNS/LNNS (linfonodo não sentinela), em 5 (7%) para 3 LNS/LNNS e em 1 (1.5%) para 4LNS/LNNS. Dos 70 pacientes, 68 (97%) apresentaram drenagem linfática ipsilateral e 2 (3%) apresentaram drenagem linfática bilateral. Em relação aos territórios de drenagem linfática dos LNS/LNNS, em 68 (97%) pacientes apresentaram drenagem para a região axilar, 1 (1,5%) para a região mamária interna e 1 (1,5%) para as regiões axilar e mamária interna. Os LNS/LNNS presentes na cadeia mamária interna não foram retirados. No intra-operatório, os cirurgiões utilizaram o corante azul patente em 35 (50%) pacientes, destes o corante identificou os LNS/LNNS em 79% dos casos. A técnica de LCINT possibilitou a visualização de todos os LNS e em alguns casos não foi possível a visualização do LNNS, o qual foi localizado e retirado com a sonda gama. Com isso, a técnica de LCINT foi eficaz em 88,5% dos casos. Dos 69 pacientes submetidos à BLNS apenas 13 (18,8%) pacientes apresentaram LNS/LNNS metastáticos, sendo estes submetidos à linfadenectomia axilar. Conclui-se que o exame pré-operatório de LCINT foi muito eficiente para o estudo da drenagem linfática, visualizando os canais linfáticos, linfonodos funcionalmente ativos e seus respectivos territórios de drenagem. Por tanto, esta técnica auxiliou o cirurgião na abordagem cirúrgica juntamente com a sonda gama intra-operatória e corante azul patente para a realização da BLNS.With the exception of non-melanoma skin cancer, the Breast cancer (breast CA) is the most incident cancer in women. In Brazil, the breast CA is more often found in South and Southeast regions. The main treatment of breast CA is the surgery. The main pathway for the tumor spreading is the lymphatic system, which may affect the regional lymph nodes. The sentinel node biopsy (SLNB) is of considerable importance, once it has a high sensitivity in identifying metastases. The technique of preoperative lymphoscintigraphy (LINCT) is essential because it allows evaluating the lymphatic drainage chain and enables the visualization of sentinel lymph node (SLN) during surgery. We aim here to describe the lymphatic drainage patterns and to evaluate the contribution of LCINT to the location of SLN in patients with breast CA. We evaluated 70 patients sequentially selected from the clinical routine, between march 2009 and august 2011, and that underwent the surgical treatment for breast CA, including the usage of the technique of LCINT for the SLN location. The LCINT were performed by the injection of four periareolar intradermal injections containing 37 MBq (1.0 mCi) of the radiopharmaceutical PHYTATE-99m-Technetium. Based on the LCINT images, we performed skin marks in the dermal projections of the SLN in all anterior/posterior, oblique and lateral views. Additionally, the gamma probe and blue dye were used to help surgeons in the surgical location of the SLN. All of the 70 patients of our study were female, ranging from 28 to 77 years, mean 54 years. The average tumor size was 1.4 cm. The most commonly found histological types were invasive ductal carcinoma (45 patients, 64.4%), followed by the in situ ductal carcinoma (16 patients, 22.8%). All LCINT procedures were well succeeded in demonstrating at least one SLN in our sample of patients. We observed lymphatic drainage for only one SLN in 43 patients (61.5%), for 2 SLN/SLNN in 21 (30%) (non sentinel lymph node), for 3 SLN/SLNN in 5 (7%) and for 4 SLN/SLNN in one patient (1.5%). From the 70 patients, 68 (97%) exhibited ipsilateral and 2 (3%) exhibited bilateral lymphatic drainage. Concerning the lymphatic territories, 68 patients (97%) exhibited drainage to SLN/SLNN in the axillary region, 1 patient (1.5%) in the internal mammary region and another patient (1.5%) in both axillary and internal mammary regions. The two SLN/SLNN found in the internal mammary chain were not removed. Complimentary to the LCINT, the surgeons used blue dye in 35 patients (50%), which enabled them to identify the SLN/SLNN in 79% of cases. On the other hand, LCINT allowed the visualization of all SLN (100%). In some cases, in which was not possible to visualize the SLNN, these ones were found by the use of the gamma probe. Thus, the LCINT technique was effective to localize the SLN in 88.5% of cases. From the 69 patients who underwent SLN biopsy, only 13 patients (18.8%) exhibited metastatic infiltration of the SLN/ SLNN. All these patients were submitted to the axillary dissection. We conclude that the preoperative LCINT was very effective for the study of lymphatic drainage, enabling the visualization of the lymphatic channels, functionally active nodes and their drainage areas. Therefore, this technique helped surgeons in the surgical approach with intraoperative gamma probe and patent blue dye for SLNB.
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Pelon, Floriane. "Fibroblastic heterogeneity and metastatic spread in breast cancers Fibroblast heterogeneity drives metastatic spread in breast cancer through distinct mechanisms." Thesis, Sorbonne Paris Cité, 2018. https://wo.app.u-paris.fr/cgi-bin/WebObjects/TheseWeb.woa/wa/show?t=2392&f=17330.
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Les cancers du sein, premiers cancers féminins et causes aujourd’hui encore de nombreux décès, sont classés en 3 sous-types moléculaires : luminaux –les plus répandus, HER2 et triple-négatifs (TN) –les plus agressifs. Lors du diagnostic, l’envahissement des ganglions lymphatiques axillaires par les cellules tumorales est établi. Il s’agit, en plus de la classification moléculaire, d’un marqueur pronostique utilisé en clinique pour stratifier les patientes, car il informe sur le risque de développement ultérieur de métastases, cause majeure des décès à l’heure actuelle. Les tumeurs solides, et notamment les cancers du sein, sont des écosystèmes complexes comprenant de nombreux types cellulaires qui interagissent avec les cellules cancéreuses. Parmi eux, les fibroblastes associés au cancer (CAF) sont les plus abondants et participent activement à de nombreux aspects de la tumorigenèse dont la croissance, l’invasion, l’angiogenèse, l’immunosuppression. Cependant, ils constituent une population hétérogène et à ce jour, très peu d’études ont analysé cette hétérogénéité tout en la liant aux diverses fonctions décrites des CAF. Dans ce projet, nous nous sommes intéressés au rôle de cette hétérogénéité fibroblastique dans la dissémination métastatique des cancers du sein. En combinant l’étude de plusieurs marqueurs de CAF, nous avons montré que les ganglions lymphatiques envahis par les cellules tumorales sont constitués de 4 sous-populations de CAF (CAF-S1, S2, S3 et S4), similaires à celles identifiées dans les tumeurs primaires appariées. De façon intéressante, ce sont les deux sous-types de CAF myofibroblastiques (αSMA+), CAF-S1 et particulièrement CAF-S4, qui s’accumulent préférentiellement dans les ganglions métastatiques. Ils présentent les mêmes signatures transcriptomiques entre les deux localisations tissulaires (ganglions envahis et tumeurs primaires correspondantes). Or, ces deux populations CAF-S1 et CAF-S4 augmentent le phénotype invasif des cellules tumorales, en régulant des fonctions complémentaires. D’un côté, les CAF-S1 sont hautement motiles, et stimulent la prolifération, la migration, l’invasion et l’initiation d’une transition épithélio-mésenchymateuse des cellules de cancer du sein. De l’autre, les CAF-S4 sont très contractiles, capables de remodeler la matrice extracellulaire et promeuvent ainsi l’invasion et la motilité des cellules tumorales dans des systèmes en 3 dimensions. Des expériences fonctionnelles suggèrent que l’action des CAF-S1 implique CXCL12 et TGFβ tandis que celle des CAF-S4 dépend de la voie NOTCH. En accord avec ces résultats, l’accumulation des CAF et leur identité dans les ganglions envahis constituent deux nouveaux facteurs pronostics dans les cancers du sein, indépendants du sous-type de cancers du sein et de l’envahissement ganglionnaire. En effet, un fort contenu en CAF-S4 y est associé avec un développement ultérieur de métastases à longue distance. Ainsi, analyser le contenu fibroblastique des ganglions axillaires au diagnostic pourrait constituer une information nouvelle et utile à la prise en charge des patientesBreast cancers are the most common cancers in women and despite great improvements in treatments, they are still responsible for many deaths worldwide. They are classified into 3 main molecular subtypes: Luminal cancers are the most frequent ones, while HER2 and TN are the most aggressive. At diagnostic, lymph node involvement is also assessed as it constitutes, in addition to molecular classification, a strong prognostic marker. Indeed, it informs on the risk to develop further distant metastases, which is the main cause of death by cancer. Solid tumors, including breast cancers, are complex ecologies comprising numerous different cell types that interact with cancer cells. Among them, cancer-associated-fibroblasts (CAF) are the most abundant and actively participate in many tumor hallmarks such as tumor growth, invasion, immunosuppression and angiogenesis. However, they do not constitute a homogeneous population but so far, only few studies have characterized this heterogeneity and linked it to CAF previously described functions. In this project, we focused on the potential involvement of CAF heterogeneity in breast cancer metastatic spread. Combining the analysis of several CAF markers, we showed that invaded LN comprise 4 CAF subsets (CAF-S1, S2, S3 and S4), similar to those found in primary tumors. Interestingly, the two myofibroblastic subsets (αSMA+) CAF-S1 and especially CAF-S4 preferentially accumulate in metastatic LN and present the same transcriptomic profiles in both tumors and LN. Importantly, both CAF-S1 and CAF-S4 display pro-invasive properties, by acting at different levels on tumor cells. On the one hand, highly motile CAF-S1 stimulate breast cancer cell proliferation, migration and EMT initiation. On the other hand, CAF-S4 exhibit an important contractility and by remodeling the matrix they are able to promote tumor cell invasion in 3D. Functional studies highlight a CXCL12/TGFβ involvement in CAF-S1 functions while CAF-S4 pro-invasive phenotype appears to be Notch-dependent. In agreement with these data, we found that CAF accumulation and subset enrichment in involved LN were two new prognostic factors, independent of breast cancer molecular subtypes and LN status at diagnosis. Indeed, stromal rich LN with a predominance of CAF-S4 are associated with long distance metastases development and poor overall survival. Thus, we propose that analyzing LN fibroblastic content at diagnosis could constitute new and useful information to breast cancer patients’ care
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McCosker, Helen Clare. "Prognostic significance of IGF and ECM induced signalling proteins in breast cancer patients." Thesis, Queensland University of Technology, 2012. https://eprints.qut.edu.au/53580/1/Helen_McCosker_Thesis.pdf.
Full textAbstract:
Breast cancer is a leading contributor to the burden of disease in Australia. Fortunately, the recent introduction of diverse therapeutic strategies have improved the survival outcome for many women. Despite this, the clinical management of breast cancer remains problematic as not all approaches are sufficiently sophisticated to take into account the heterogeneity of this disease and are unable to predict disease progression, in particular, metastasis. As such, women with good prognostic outcomes are exposed to the side effects of therapies without added benefit. Furthermore, women with aggressive disease for whom these advanced treatments would deliver benefit cannot be distinguished and opportunities for more intensive or novel treatment are lost. This study is designed to identify novel factors associated with disease progression, and the potential to inform disease prognosis. Frequently overlooked, yet common mediators of disease are the interactions that take place between the insulin-like growth factor (IGF) system and the extracellular matrix (ECM).
Our laboratory has previously demonstrated that multiprotein insulin-like growth factor-I (IGF-I): insulin-like growth factor binding protein (IGFBP): vitronectin (VN) complexes stimulate migration of breast cancer cells in vitro, via the cooperative involvement of the insulin-like growth factor type I receptor (IGF-IR) and VN-binding integrins. However, the effects of IGF and ECM protein interactions on the dissemination and progression of breast cancer in vivo are unknown. It was hypothesised that interactions between proteins required for IGF induced signalling events and those within the ECM contribute to breast cancer metastasis and are prognostic and predictive indicators of patient outcome.
To address this hypothesis, semiquantitative immunohistochemistry (IHC) analyses were performed to compare the extracellular and subcellular distribution of IGF and ECM induced signalling proteins between matched normal, primary cancer, and metastatic cancer among archival formalin-fixed paraffin-embedded (FFPE) breast tissue samples collected from women attending the Princess Alexandra Hospital, Brisbane. Multivariate Cox proportional hazards (PH) regression survival models in conjunction with a modified „purposeful selection of covariates. method were applied to determine the prognostic potential of these proteins.
This study provides the first in-depth, compartmentalised analysis of the distribution of IGF and ECM induced signalling proteins. As protein function and protein localisation are closely correlated, these findings provide novel insights into IGF signalling and ECM protein function during breast cancer development and progression. Distinct IGF signalling and ECM protein immunoreactivity was observed in the stroma and/or in subcellular locations in normal breast, primary cancer and metastatic cancer tissues. Analysis of the presence and location of stratifin (SFN) suggested a causal relationship in ECM remodelling events during breast cancer development and progression. The results of this study have also suggested that fibronectin (FN) and ¥â1 integrin are important for the formation of invadopodia and epithelial-to-mesenchymal transition (EMT) events. Our data also highlighted the importance of the temporal and spatial distribution of IGF induced signalling proteins in breast cancer metastasis; in particular, SFN, enhancer-of-split and hairy-related protein 2 (SHARP-2), total-akt/protein kinase B 1 (Total-AKT1), phosphorylated-akt/protein kinase B (P-AKT), extracellular signal-related kinase-1 and extracellular signal-related kinase-2 (ERK1/2) and phosphorylated-extracellular signal-related kinase-1 and extracellular signal-related kinase-2 (P-ERK1/2).
Multivariate survival models were created from the immunohistochemical data. These models were found to fit well with these data with very high statistical confidence. Numerous prognostic confounding effects and effect modifications were identified among elements of the ECM and IGF signalling cascade and corroborate the survival models. This finding provides further evidence for the prognostic potential of IGF and ECM induced signalling proteins. In addition, the adjusted measures of associations obtained in this study have strengthened the validity and utility of the resulting models.
The findings from this study provide insights into the biological interactions that occur during the development of breast tissue and contribute to disease progression. Importantly, these multivariate survival models could provide important prognostic and predictive indicators that assist the clinical management of breast disease, namely in the early identification of cancers with a propensity to metastasise, and/or recur following adjuvant therapy. The outcomes of this study further inform the development of new therapeutics to aid patient recovery. The findings from this study have widespread clinical application in the diagnosis of disease and prognosis of disease progression, and inform the most appropriate clinical management of individuals with breast cancer.
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Teixeira, Patricia Akissue de Camargo. "Desempenho da ultrassonografia e da punção aspirativa por agulha fina axilar em pacientes com carcinomas invasivos da mama: correlação com aspectos do linfonodo e características tumorais." Universidade de São Paulo, 2017. http://www.teses.usp.br/teses/disponiveis/5/5151/tde-14112017-162244/.
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INTRODUÇÃO: O status linfonodal da axila ainda permanece como importante fator prognóstico em pacientes com câncer de mama invasivo. Muitos estudos já relataram a importância da ultrassonografia axilar e da punção aspirativa por agulha fina (PAAF) na avaliação pré-operatória das pacientes com câncer de mama. Nossos objetivos foram avaliar as características ultrassonográficas dos linfonodos axilares relacionadas à metástase linfonodal e o papel da PAAF na avaliação pré-operatória de pacientes com câncer de mama. Nosso objetivo secundário foi avaliar se, dependendo das características dos tumores, linfonodos sem alterações na ultrassonografia poderiam ter comprometimento metastático. MÉTODOS: Este estudo foi realizado no Instituto de Radiologia e no Instituto do Câncer do HCFMUSP. Foram incluídas 182 pacientes com câncer de mama invasivo recém-diagnosticado, sendo que, destas, apenas 145 realizaram cirurgia - 74 prosseguiram direto para cirurgia e 71 realizaram tratamento neoadjuvante e após cirurgia. Foi realizada avaliação ultrassonográfica da axila ipsilateral ao tumor e punção aspirativa por agulha fina de um linfonodo selecionado pelo radiologista. Os dados ultrassonográficos dos linfonodos e os achados citológicos da PAAF foram correlacionados com os resultados anatomopatológicos da biópsia do linfonodo sentinela ou do esvaziamento axilar. RESULTADOS: Nas 74 pacientes (75 axilas) que não realizaram tratamento neoadjuvante, as características ultrassonográficas do linfonodo associadas à metástase na análise univariada foram espessamento cortical difuso e a obliteração parcial ou completa do hilo gorduroso. A sensibilidade, especificidade, acurácia, valor preditivo positivo (VPP) e valor preditivo negativo (VPN) da ultrassonografia foram, respectivamente, 72,7%, 57,1%, 64,0%, 57,1% e 72,7% (p=0,009), e da PAAF: 36,4%, 97,6%, 70,7%, 92,3% e 66,1% (p < 0,001). Incluindo apenas linfonodos alterados na ultrassonografia, obtivemos, respectivamente, sensibilidade, especificidade, acurácia, VPP e VPN de 50%, 94%, 69%, 92% 59% (p=0,001). Nenhuma PAAF de linfonodo classificado como normal na ultrassonografia teve resultado positivo. Obtivemos, nas análises das curvas ROC, um valor de corte da espessura da cortical de 2,65 mm (p < 0,001) e do tamanho do tumor pré-cirúrgico de 2,45 cm (p=0,042). Na análise multivariada, as seguintes características foram associadas à metástase linfonodal: espessura da cortical (p = 0,005), tamanho do tumor pré-cirúrgico (p = 0,030), status pré-menopausa (p = 0,017), tipo histológico não especial (p = 0,034) e localização do tumor no quadrante superolateral (p = 0,011). Construiu-se um modelo de predição de risco de metástase axilar usando estas características. Nas 71 pacientes que realizaram tratamento adjuvante, a única característica do linfonodo associada à metástase linfonodal foi a forma redonda ou irregular. Os demais resultados deste grupo não podem ser generalizados, pois não é possível separar o efeito do tratamento nesta população. CONCLUSÕES: Linfonodos axilares com espessamento cortical difuso e com obliteração parcial ou completa do hilo gorduroso estão associados à malignidade. A PAAF apresentou-se mais útil nos linfonodos alterados, com sensibilidade de 50%. Pacientes com PAAF positivas devem ser encaminhadas para esvaziamento axilar ou quimioterapia neoadjuvante. Não há benefício da realização da PAAF em linfonodos sem alterações na ultrassonografiaBACKGROUND: The lymph node status of the axilla remains an important prognostic factor in patients with invasive breast cancer. Many studies have already reported the importance of axillary ultrasonography and fine needle aspiration (FNA) in the preoperative evaluation of patients with breast cancer. Our objectives were to evaluate the ultrasound characteristics of axillary lymph nodes related to lymph node metastasis and the role of FNA in the preoperative evaluation of patients with breast cancer. Our secondary objective was to assess whether, depending on the tumor characteristics, lymph nodes that showed no change on ultrasonography could have metastatic involvement. METHODS: This study was conducted at the Institute of Radiology and the Institute of Cancer of HCFMUSP. A total of 182 patients with newly diagnosed invasive breast cancer were included, of whom only 145 had undergone surgery - 74 went straight to surgery and 71 underwent neoadjuvant treatment and after surgery. Ultrasound evaluation of the axilla ipsilateral to the tumor and fine needle aspiration of a lymph node selected by the radiologist were performed. The ultrasound data of the lymph nodes and the cytological findings of FNA were correlated with pathology results from sentinel lymph node biopsy or surgical dissection. RESULTS: In the 74 patients (75 axillae) who did not undergo neoadjuvant treatment, the ultrasound characteristics of the lymph nodes associated with metastasis in the univariate analysis were diffuse cortical thickening and partial or complete fatty hilum obliteration. The sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) of ultrasound were respectively 72.7%, 57.1%, 64.0%, 57.1% and 72.7% (p = 0.009) and of the FNA 36.4%, 97.6%, 70.7%, 92.3% and 66.1% (p <0.001). Including only atypical lymph nodes on ultrasonography, we obtained respectively sensitivity, specificity, accuracy, PPV and NPV of 50%, 94%, 69% 92% and 59% (p = 0.001). No FNA of lymph node classified as normal on ultrasonography had a positive result. With ROC curves analysis we obtained a cut-off value of cortical thickness of 2.65 mm (p <0.001) and pre-surgical tumor size of 2.45 cm (p = 0.042). In the multivariate analysis, the following characteristics were associated with lymph node metastasis: cortical thickness (p = 0.005), preoperative tumor size (p = 0.030), premenopausal status (p = 0.017), non-special histological type and tumor location in the upper outer quadrant (p = 0.011). A predictive model of axillary metastasis risk was constructed using these characteristics. In the 71 patients who underwent adjuvant treatment the only feature of the lymph node associated with lymph node metastasis was the round or irregular shape. The other results of this group cannot be generalized since it is not possible to separate the treatment effect in this population. CONCLUSIONS: Axillary lymph nodes with diffuse cortical thickening and with partial or complete fatty hilum obliteration are associated with malignancy. FNA was more useful in atypical lymph nodes, with a sensitivity of 50%. Patients with positive FNA should be referred for axillary surgical dissection or neoadjuvant chemotherapy. There is no benefit of performing FNA in lymph nodes without changes in ultrasound
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Peña, González Karla. "Estudio del ganglio centinela por método molecular en pacientes con cáncer de mama y axila clínicamente negativa que han recibido quimioterapia neoadyuvante." Doctoral thesis, Universitat Rovira i Virgili, 2018. http://hdl.handle.net/10803/664575.
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Antecedents: El càncer de mama és el tumor més freqüent en les dones occidentals. En les últimes dècades s'ha reconegut i estudiat l'heterogeneïtat dels carcinomes de mama, i mitjançant l'ús d'anàlisi de l'expressió gènica, s'han pogut identificar diversos subtipus moleculars i en la pràctica clínica diària s'ha adaptat l'ús de marcadors immunohistoquímics per identificar-los de manera rutinària. La quimioteràpia neoadjuvant (QNA) s'ha utilitzat àmpliament per tractar el càncer de mama i la resposta d'un tumor al tractament sistèmic es relaciona amb un increment en la supervivència a llarg termini. Així mateix estat dels ganglis limfàtics axil·lars continua sent el factor pronòstic més important per a les pacients amb càncer de mama en estadi d'hora.
Mètodes: estudi de cohort retrospectiu i descriptiu, que incloc 92 pacients diagnosticades de càncer de mama invasiu estadis CT2-cT3 cN0, les quals van ser sotmeses a QNA i posteriorment a cirurgia amb biòpsia selectiva del gangli sentinella (BSGS) pel mètode de Osna a l'Hospital Universitari Sant Joan de Reus . De la base de dades del servei d'Anatomia Patològica es van recopilar dades com el grau tumoral, el tipus histològic, la resposta patològica del tumor a la QNA, el nombre total de GC obtinguts, el nombre de còpies d'àcid ribonucleic missatger (ARNm) de CK19 i l'estat dels ganglis axil·lars no sentinelles.
Resultats: El subtipus tumoral intrínsec més observat va ser el Luminal B (61,96%). La resposta patològica del tumor al tractament sistèmic va ser parcial en 59 casos (65,22%), completa en 28 (30,44%) i no es va observar resposta en 5 casos (4,35%). El Gc va ser positiu en 38 pacients i en 6 d'elles es van trobar més ganglis axil·lars no sentinelles positius. Totes elles van presentar tumors del subtipus Luminal B amb una resposta patològica parcial.
Conclusió: Les pacients que presenten el GC positiu però mostren una RPC a la mama poden tenir una baixa probabilitat de presentar mes ganglis no sentinelles afectes a l'aixella.Antecedentes: El cáncer de mama es el tumor más frecuente en las mujeres occidentales. En las últimas décadas se ha reconocido y estudiado la heterogeneidad de los carcinomas de mama, y mediante el uso de análisis de la expresión génica , se han podido identificar varios subtipos moleculares y en la práctica clínica diaria se ha adaptado el uso de marcadores inmunohistoquímicos para identificarlos de manera rutinaria. La quimioterapia neoadyuvante (QNA) se ha utilizado ampliamente para tratar el cáncer de mama y la respuesta de un tumor al tratamiento sistémico se relaciona con un incremento en la supervivencia a largo plazo. Así mismo estado de los ganglios linfáticos axilares continúa siendo el factor pronóstico más importante para las pacientes con cáncer de mama en estadio temprano. Métodos:estudio de cohorte retrospectivo y descriptivo, que incluyo 92 pacientes diagnosticadas de cáncer de mama invasivo estadios cT2-cT3 cN0, las cuales fueron sometidas a QNA y posteriormente a cirugía con biopsia selectiva del ganglio centinela (BSGC) por el método de OSNA en el Hospital Universitario Sant Joan de Reus. De la base de datos del servicio de Anatomía Patológica se recopilaron datos como el grado tumoral, el tipo histológico, la respuesta patológica del tumor a la QNA, el número total de GC obtenidos, el número de copias de ácido ribonucleico mensajero (ARNm) de CK19 y el estado de los ganglios axilares no centinelas. Resultados:El subtipo tumoral intrínseco más observado fue el Luminal B (61,96%).La respuesta patológica del tumor al tratamiento sistémico fue parcial en 59 casos (65,22%), completa en 28 (30,44%) y no se observó respuesta en 5 casos (4,35%). El Gc fue positivo en 38 pacientes y en 6 de ellas se hallaron más ganglios axilares no centinelas positivos. Todas ellas presentaron tumores del subtipo Luminal B con una respuesta patológica parcial. Conclusión:Las pacientes que presentan el GC positivo pero muestran una RPc en la mama pueden tener una baja probabilidad de presentar mas ganglios no centinelas afectos en la axila.
Background: Breast cancer is the most frequent tumor in Western women. In the last decades the heterogeneity of breast carcinomas has been recognized and studied, and through the use of gene expression analysis, several molecular subtypes have been identified and the use of immunohistochemical markers has been adapted in daily clinical practice identify them routinely. Neoadjuvant chemotherapy (NAC) has been widely used to treat breast cancer and the response of a tumor to systemic treatment is related to an increase in long-term survival. Likewise, axillary lymph node status continues to be the most important prognostic factor for patients with early-stage breast cancer. Methods: retrospective and descriptive cohort study, which included 92 patients diagnosed with invasive breast cancer cT2-cT3 cN0 stages, who underwent NAC and then surgery with selective biopsy of sentinel lymph node (SLNB) by the OSNA method at the University Hospital Sant Joan de Reus . From the database of the Pathology deparment, data were collected such as the tumor grade, the histological type, the pathological response of the tumor to the NAC, the total number of SLN obtained, the number of copies of messenger ribonucleic acid (mRNA) from CK19 and the status of axillary nodes sentinels. Results: The most observed intrinsic tumoral subtype was Luminal B (61.96%) .The pathological response of the tumor to systemic treatment was partial in 59 cases (65.22%), complete in 28 (30.44%) and not response was observed in 5 cases (4.35%). The Gc was positive in 38 patients and in 6 of them more axillary no sentinel lymph nodes were found. All of them presented tumors of the Luminal B subtype with a partial pathological response. Conclusion: Patients who present positive GC but show an RPc in the breast may have a low probability of presenting more no sentinel lymph nodes affected in the axilla.
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Antonio, Heriton Marcelo Ribeiro. "Linfonodo sentinela e dissecção axilar: análise da disfunção de membros superiores." Universidade de São Paulo, 2011. http://www.teses.usp.br/teses/disponiveis/17/17145/tde-05012016-104011/.
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O câncer de mama é a neoplasia maligna que mais acomete as mulheres na população brasileira. Atualmente o tratamento para o câncer de mama está fundamentado em três pilares: radioterapia, cirurgia em suas diversas técnicas, quimioterapia/hormonioterapia. A qualidade de vida pode ser afetada de uma forma geral, envolvendo os aspectos físicos, psicológicos, sociológicos, emocionais, entre outros. O objetivo deste estudo foi comparar a função do membro superior em pacientes com câncer de mama que foram submetidas à biópsia de linfonodo sentinela com as submetidas à dissecção axilar, e que não foram acompanhadas por um protocolo de reabilitação pré-estabelecido. Pacientes e métodos: foram avaliadas 36 pacientes que passaram por dissecção axilar (grupo DA), 29 que foram submetidas à biópsia de linfonodo sentinela (grupo BLS) e 11 sujeitos normais (grupo SN). Resultados: Verificamos que o grupo DA apresenta um risco de ter perda funcional para os movimentos de flexão e abdução de ombro na ordem de 5 e 3,7 vezes maior que o grupo BLS, respectivamente. Encontramos também que pacientes submetidas à BLS evoluem com disfunção significativa para a flexão e abdução de ombro quando não submetidas à intervenção fisioterápica. Conclusão: A DA apresenta uma maior disfunção em membro superior quando comparada com BLS. A reabilitação de pacientes submetidas à BLS não pode ser ignorada, pois esta intervenção cirúrgica pode levar a disfunção significativa do membro superior ipsilateralBreast cancer is a malignancy that affects more women in the Brazilian population. Currently the treatment for breast cancer is based on three pillars: radiotherapy, surgery in its various techniques, chemotherapy / hormone therapy. Quality of life may be affected in general, involving the physical, psychological, sociological, emotional, and others. The aim of this study was to compare the upper limb function in patients with breast cancer who underwent sentinel lymph node biopsy with axillary dissection underwent, and were not accompanied by a rehabilitation protocol pre-established. Patients and methods: we evaluated 36 patients who underwent axillary dissection (group DA), 29 who underwent sentinel lymph node biopsy (SNB group) and 11 normal subjects (group SN). Results: We found that the DA group presents a risk of loss of function for flexion and shoulder abduction in the order of 5 and 3.7 times higher than the BLS group, respectively. We also found that patients who underwent SNB evolve with significant dysfunction for flexion and shoulder abduction when not undergoing physiotherapy intervention. Conclusion: The DA has a higher dysfunction in upper limb when compared with BLS. The rehabilitation of patients who underwent SNB can not be ignored because this surgery can lead to significant dysfunction of the ipsilateral upper limb
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Morais, Fernanda Dorneles de. "Qualidade de vida e morbidade tardia após a biópsia do linfonodo sentinela ou linfadenectomia axilar em mulheres submetidas ao tratamento do câncer de mama." Universidade Federal de Goiás, 2014. http://repositorio.bc.ufg.br/tede/handle/tede/6442.
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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES
The aim of this study was to evaluate quality of life (QoL) and late morbidity after axillary lymphadenectomy (AL) or sentinel lymph node biopsy (SLNB) in breast cancer survivors. :This was an analytical, cross-sectional study with 100 participants. Sociodemographic and clinical data were obtained at interviews, from patients’ medical charts and by applying the EORTC QLQ-C30 and QLQ-BR23 questionnaires. In addition, a kinetic analysis was made of the patients’ upper limb function to investigate the presence of possible late morbidities (pain, limited range of motion [ROM], sensory disturbance and lymphedema). Results: The patients who underwent AL worse QoL than those submitted to SLNB in 10 domains. Following AL, there was a greater likelihood of the patient developing: lymphedema (odds ratio [OR]: 17.22; 95% confidence interval [95%CI]: 2.15-137.57), reduced flexion (OR: 6; 95%CI: 2.45-14.68), reduced abduction (OR: 5.67; 95%CI: 2.14–15.00), sensory disturbance (OR: 4.03; 95%CI: 1.71–9.49) and pain (OR: 1.74; 95%CI: 1.16–2.61). Conclusions: These results confirm the benefit of SLNB due to its lower arm morbidity impact on QoL, compared with AL. All morbidities were more common and more likely to occur in the patients submitted the dissection axillary. In addition, the high frequency of limitations in movement and pain in both groups merits particular attention.
O objetivo desse estudo foi avaliar a qualidade de vida (QV) e morbidades após linfadenectomia axilar (LA) ou biópsia de linfonodo sentinela (BLS) em sobreviventes do câncer de mama. Trata-se de um estudo transversal, analítico, composto por 100 participantes. Os dados pessoais, sociodemográficos e clínicos foram obtidos por meio de entrevista, dados dos prontuários e aplicação dos questionários EORTC QLQ C 30 e BR 23. Além disso, foi realizada avaliação cinético funcional dos membros superiores das pacientes para verificar a presença de possíveis morbidades tardias (dor, limitação na amplitude de movimento (ADM), alteração na sensibilidade e linfedema). Resultados: As pacientes que se submeteram à LA apresentaram pior QV do que aqueles submetidos à biópsia de linfonodo sentinela em 10 domínios. Após a LA foi maior a probabilidade de ocorrer linfedema (OR 17,22; IC 95% 2,15-137,57), déficit de flexão (OR 6; IC 95% 2,45-14,68), déficit de abdução (OR 5,67; IC 95% 2,14-15,00), alteração na sensibilidade (OR 4,03; IC 95% 1,71-9,49) e dor (OR 1,74; IC 95% 1,16-2,61). Conclusões: Estes resultados confirmam o benefício da BLS devido ao seu menor impacto na morbidade pós-operatória e na qualidade de vida, em comparação com LA. Todas as morbidades foram mais frequentes e tiveram maior risco de ocorrerem em pacientes submetidos a esvaziamento axilar. Além disso, a alta frequência nas limitações de movimento e dor, em ambos os grupos, merecem atenção especial.
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Bosch, Príncep Ramon. "Cel·lularitat immune als ganglis limfàtics axil·lars negatius en pacients amb càncer de mama." Doctoral thesis, Universitat Rovira i Virgili, 2020. http://hdl.handle.net/10803/670599.
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Introducció: Les cèl·lules tumorals poden modificar la resposta immune en tumors primaris i en els ganglis limfàtics axil·lars amb metàstasis (GLA+) en el càncer de mama (CM), la qual cosa influeix en l'evolució de la pacient. Investiguem si els patrons de cèl·lules immunes en el tumor primari i en els ganglis limfàtics axil·lars sense metàstasi (GLA-) difereixen entre les pacients diagnosticades sense GLA+ (pdGLA-) i amb GLA+ (pdGLA+) i les implicacions per a l'evolució clínica.
Material i mètodes: Es van estudiar 11 marcadors immunes utilitzant immunohistoquímica, matrius multiteixit i anàlisi d'imatges digitals en 141 mostres de pacients amb CM (75 pdGLA+ i 66 pdGLA-). Es van elaborar dos models de regressió logística per identificar les variables clíniques, patològiques i immunològiques associades amb la presència de GLA+ en el moment del diagnòstic.
Resultats: Les pdGLA+ van tenir tumors significativament més grans, percentatges més alts d'invasió limfovascular i perineural i un grau histològic més alt que les pdGLA-. Vam trobar diversos patrons immunes al GLA- associats amb la presència de GLA+ en el moment del diagnòstic. Els models de regressió van mostrar un petit subgrup de pdGLA+ amb patrons immunes al GLA- que eren més similars als de GLA- de les pdGLA-. Aquest petit subgrup també va mostrar un comportament clínic similar al de les pdGLA-. Es va trobar un altre petit subgrup de pdGLA- amb patrons immunes al GLA- més similars als del GLA- de les pdGLA+. Aquest petit subgrup va tenir un comportament clínic similar a les pdGLA+.
Discussió: Aquestes dades suggereixen que algunes poblacions immunes presents en GLA- en el moment del diagnòstic estan associades a la presència de metàstasi al GLA en el moment de la diagnosi, però també queda palès que podrien influir en l'evolució clínica de les pacients amb CM.Introducción: Las células tumorales pueden modificar la respuesta inmune en tumores primarios y en los ganglios linfáticos axilares con metástasis (GLA+) en el cáncer de mama (CM), lo que influye en la evolución de la paciente. Investigamos si los patrones de células inmunes en el tumor primario y en los ganglios linfáticos axilares sin metástasis (GLA-) difieren entre las pacientes diagnosticadas sin GLA+ (pdGLA-) y con GLA+ (pdGLA+) y las implicaciones para la evolución clínica. Material y métodos: Se estudiaron once marcadores inmunes utilizando inmunohistoquímica, matrices multitejido y análisis de imágenes digitales en 141 muestras de pacientes con CM (75 pdGLA+ y 66 pdGLA-). Se elaboraron dos modelos de regresión logística para identificar las variables clínicas, patológicas e inmunológicas asociadas con la presencia de GLA+ en el momento del diagnóstico. Resultados: Las pdGLA+ tuvieron tumores significativamente más grandes, porcentajes más altos de invasión linfovascular y perineural y un grado histológico más alto que las pdGLA-. Encontramos varios patrones inmunes en el GLA- asociados con la presencia de GLA+ en el momento del diagnóstico. Los modelos de regresión mostraron un pequeño subgrupo de pdGLA+ con patrones inmunes en el GLA- que eran más similares a los del GLA- de las pdGLA-. Este pequeño subgrupo también mostró un comportamiento clínico similar al de las pdGLA-. Se encontró otro pequeño subgrupo de pdGLA- con patrones inmunes en el GLA- más similares a los del GLA- de las pdGLA+. Este pequeño subgrupo tuvo un comportamiento clínico similar al pdGLA+. Discusión: Estos datos sugieren que algunas poblaciones inmunes presentes en GLA- en el momento del diagnóstico están asociadas a la presencia de metástasis en el GLA en el momento del diagnóstico, pero también queda patente que podrían influir en la evolución clínica de las pacientes con CM.
ntroduction: Tumor cells can modify the immune response in primary tumors and in the axillary lymph nodes with metastasis (ALN+) in breast cancer (BC), influencing patient outcome. We investigated whether patterns of immune cells in the primary tumor and in the axillary lymph nodes without metastasis (ALN-) differed between patients diagnosed without ALN+ ( pdALN-) and with ALN+ (pdALN+) and the implications for clinical outcome. Material and methods: Eleven immune markers were studied using immunohistochemistry, tissue microarray, and digital image analysis in 141 BC patient samples (75 pdALN+ and 66 pdALN-). Two logistic regression models were derived to identify the clinical, pathologic, and immunologic variables associated with the presence of ALN+ at diagnosis. Results: PdALN+ had significantly larger tumors, higher percentages of lymphovascular and perineural invasion and a higher histologic grade than pdALN-. We found several immune patterns in the ALN- associated with the presence of ALN+ at diagnosis. The regression models revealed a small subgroup of pdALN+ with ALN- immune patterns that were more similar to those of the ALN- of the pdALN-. This small subgroup also showed similar clinical behavior to that of the pdALN-. Another small subgroup of pdALN- with ALN- immune patterns was found whose members were more similar to those of the ALN- of the pdALN+. This small subgroup had similar clinical behavior to the pdALN+. Discussion: These data suggest that some immune populations present in ALN- at diagnosis are associated with having metastasis in the ALN at diagnosis but also highlight that they could influence the clinical outcome of BC patients.
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Hamy, Anne-Sophie. "Identification of Factors Predicting Sensitivity or Resistance to Neoadjuvant Chemotherapy in Breast Cancer Neoadjuvant treatment : the future of patients with breast cancer Neoadjuvant treatment for intermediate/high-risk HER2-positive and triple-negative breast cancers: no longer an “option” but an ethical obligation Long-term outcome of the REMAGUS 02 trial, a multicenter randomised phase II trial in locally advanced breast cancer patients treated with neoadjuvant chemotherapy with or without celecoxib or trastuzumab according to HER2 status BIRC5 (survivin) : a pejorative prognostic marker in stage II/III breast cancer with no response to neoadjuvant chemotherapy Beyond Axillary Lymph Node Metastasis, BMI and Menopausal Status Are Prognostic Determinants for Triple-Negative Breast Cancer Treated by Neoadjuvant Chemotherapy Pathological complete response and prognosis after neoadjuvant chemotherapy for HER2-positive breast cancers before and after trastuzumab era: results from a real-life cohort The presence of an in situ component on pre-treatment biopsy is not associated with response to neoadjuvant chemotherapy for breast cancer Chemosensitivity, tumor infiltrating lymphocytes (TILs), and survival of postpartum PABC patients treated by neoadjuvant chemotherapy Lymphovascular invasion after neoadjuvant chemotherapy is strongly associated with poor prognosis in breast carcinoma New insight for pharmacogenomics studies from the transcriptional analysis of two large-scale cancer cell line panels Biological network-driven gene selection identifies a stromal immune module as a key determinant of triple-negative breast carcinoma prognosis A Stromal Immune Module Correlated with the Response to Neoadjuvant Chemotherapy, Prognosis and Lymphocyte Infiltration in HER2-Positive Breast Carcinoma Is Inversely Correlated with Hormonal Pathways Stromal lymphocyte infiltration after neoadjuvant chemotherapy is associated with aggressive residual disease and lower disease-free survival in HER2-positive breast cancer Interaction between molecular subtypes, stromal immune infiltration before and after treatment in breast cancer patients treated with neoadjuvant chemotherapy COX2/PTGS2 Expression Is Predictive of Response to Neoadjuvant Celecoxib in HER2-negative Breast Cancer Patients Celecoxib With Neoadjuvant Chemotherapy for Breast Cancer Might Worsen Outcomes Differentially by COX-2 Expression and ER Status: Exploratory Analysis of the REMAGUS02 Trial Comedications influence immune infiltration and pathological response to neoadjuvant chemotherapy in breast cancer." Thesis, Université Paris-Saclay (ComUE), 2019. http://www.theses.fr/2019SACLS129.
Full textAbstract:
La chimiothérapie néoadjuvante (CNA) est utilisée dans les cancers du sein agressifs ou localement avancés (CS). Au delà des bénéfices cliniques, elle représente une opportunité pour monitorer in vivo la sensibilité d’une tumeur à un traitement.A partir de l’analyse de sets de données de patients traités par CNA, nous souhaitons identifier des mécanismes associes à la résistance ou sensibilité au traitement. Dans la première partie, nous avons évalué des paramètres, cliniques, anatomopathologiques et transcriptomiques. Nous avons démontré que des éléments non explorés comme la présence d’embols après CNA revêtaient une information pronostique importante. Dans une 2ème partie, nous avons analysé l’impact de l’infiltrat immunitaire dans le cancer du sein, et avons décrit les changements observés entre des échantillons avant et après CNA. Nous avons montré que l’impact pronostique des TILs était différent avant et après CNA, et était opposé dans les CS triple négatif ou HER2-positif. Finalement, nous avons analysé l’impact des comédications pendant la CNA. Nous avons trouvé des effets positifs – via l’augmentation de l’infiltrat immunitaire et la réponse au traitement – et des effets négatifs avec des effets délétères dans certains sous groupes de patients. En conclusion, la situation néoadjuvante représente une plateforme pour générer et potentiellement valider des hypothèses de recherche. La mise à disposition de jeux de données de patients traités par chimiothérapie néoadjuvante constituerait une ressource majeure pour accélérer la recherche contre le cancer du seinNeoadjuvant chemotherapy (NAC i.e. chemotherapy before surgery) is increasingly being used for aggressive or locally advanced breast cancer (BCs). Beyond clinical benefits, it represents an opportunity to monitor in vivo sensitivity to treatment. Based on the analysis of datasets of BCs patients treated with NAC, we aimed at identifying mechanisms associated with resistance or sensitivity to treatment.In the first part, we evaluated biological, clinical, pathological and transcriptomic patterns. We demonstrated that unexplored pathological features such as post-NAC lymphovascular invasion may carried an important prognostic information.In a second part, we analyzed impact of imune infiltration in BC and we described extensively the changes of tumor infiltrating lymphocytes (TILs) between pre and post-NAC samples. We showed that the prognostic impact of TILs was different before and after NAC, and was opposite in TNBC and HER2-positive BCs. Finally, we investigated the impact of comedications use during NAC. We found both positive effects - while enhancing immune infiltration and response to treatment - and negative effects with deleterisous oncologic outcomes in specific patients subgroups. In conclusion, the neoadjuvant setting represents a platform to both generate and potentially validate research hypotheses aiming at increasing the efficacy of treatment. The public release of real-life datasets of BC patients treated with NAC would represent a major resource to accelerate BC research
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Eleutério, Ricardo Jorge Neves. "Microwave imaging of the axilla to aid breast cancer diagnosis." Master's thesis, 2014. http://hdl.handle.net/10362/13658.
Full textAbstract:
Breast cancer is the most common type of cancer among women all over the world.
An important issue that is not commonly addressed in breast cancer imaging literature is the importance of imaging the underarm region—where up to 80% of breast cancer cells can metastasise to. The first axillary lymph nodes to receive drainage from the primary tumour in the breast are called Sentinel Node. If cancer cells are found in the Sentinel Node, there is an increased risk of metastatic breast cancer which makes this evaluation crucial to decide what follow-up exams and therapy to follow. However, non-invasive detection of cancer cells in the lymph nodes is often inconclusive, leading to the surgical
removal of too many nodes which causes adverse side-effects for patients.
Microwave Imaging is one of the most promising non-invasive imaging modalities
for breast cancer early screening and monitoring. This novel study tests the feasibility of imaging the axilla region by means of the simulation of an Ultra-Wideband Microwave Imaging system. Simulations of such system are completed in several 2D underarm models that mimic the axilla. Initial imaging results are obtained by means of processing the simulated backscattered signals by eliminating artefacts caused by the skin and beamforming
the processed signals in order to time-align all the signals recorded at each antenna.
In this dissertation several image formation algorithms are implemented and compared
by visual inspection of the resulting images and through a range of performance metrics, such as Signal-to-Clutter Ratio and FullWidth Half Maximum calculations.
The results in this study showed that Microwave Imaging is a promising technique
that might allow to identify the presence and location of metastasised cancer cells in
axillary lymph nodes, enabling the non-invasive evaluation of breast cancer staging.
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Louis, Kristine Sarah. "Characterization of ZHX1 in Axillary Lymph Node-negative Breast Cancer." Thesis, 2012. http://hdl.handle.net/1807/32603.
Full textAbstract:
Women with breast cancer without local metastasis to the axillary lymph nodes (axillary lymph node-negative, ANN) have a good prognosis. However, 20 to 30% of patients with ANN breast cancer will still experience recurrence and distant metastases. Lymphatic invasion (LVI) is an important prognostic factor for ANN breast cancer. Zinc fingers and homeoboxes 1 (ZHX1) was identified as a candidate gene involved in LVI and associated with early recurrence of ANN breast cancer. I examined expression of ZHX1 in breast cancer cell lines and ANN breast tumour samples and discovered that it is expressed at variable levels. I also investigated ZHX1 copy number and determined that amplification does not appear to be a mechanism of its over-expression. From bioinformatic and proteomic analyses, ZHX1 was discovered to potentially be phosphorylated. Overall, these studies suggest that ZHX1 may be involved in ANN breast cancer.
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Wells, Bryan John. "A Comparison of the Costs of Sentinel Lymph Node Biopsy and of Axillary lymph Node Dissection in the Management of Early-stage Breast Cancer in Ontario." Thesis, 2009. http://hdl.handle.net/1807/18993.
Full textAbstract:
Objective: To complete a cost-minimization analysis (CMA) of the cost of sentinel lymph node biopsy (SLNB) and axillary lymph node dissection (ALND) in the management of early-stage breast cancer (ESBC) in a hypothetical Ontario hospital setting.
Methods: Decision-analysis modeling, with a decision-tree and Markov states, was used to estimate hospital costs for the two treatment options. The model was populated with data from the literature and costs from the Ontario Case Costing Initiative, a publicly accessible, government-sponsored, costing database. Model variability and parameter uncertainty were quantified by probabilistic sensitivity analysis (PSA).
Results: The SLNB treatment algorithm was cost-minimizing compared to the ALND-only treatment option. The costs of treating postoperative complications did not contribute to the incremental average cost.
Conclusion: A treatment algorithm that involves SLNB as the initial axillary-staging procedure in the setting of ESBC offers a cost-savings over the ALND-only option. This result is generalizable to all Ontario hospitals.
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Hung, Chin-Sheng, and 洪進昇. "High expression of CXCR4 in HER2 negative breast cancer patient may contribute to lymph node metastasis." Thesis, 2008. http://ndltd.ncl.edu.tw/handle/70078996122203709811.
Full textAbstract:
碩士國立臺灣大學
臨床醫學研究所
96
Purposes of the study: Lymph node metastasis is an important prognostic factor in breast cancer, and lymph node metastasis may be the initial step for further distal metastasis. Therefore, identifying the contributing factors of lymph node metastasis in breast cancer may be helpful to understand the mechanism of metastasis. CXC chemokine receptor 4（CXCR4）is a member of chemokine receptor which is mostly expressed in immune cells. However, many studies report the expression in cancer cell and the relationship between cancer metastasis and CXCR4 expression. So, our study is to identify the correlation between the CXCR4 expression and axillary lymph node metastasis. This study investigate the influence of hormone receptor and HER2/neu expression. Material and method: Patients who had distal metastasis, T4 or N3 stage breast cancer, predominant ductal carcinoma in situ, received neoadjuvant chemotherapy or no lymph node data available were excluded. Eighty breast cancer patients between January 2006 and December 2006 were enrolled. All patients received the breast surgery and axillary lymph node dissection or sentinel lymph node sampling. Breast cancer tissue fixed with formalin and embedded with paraffin was obtained and stained with anti-CXCR4 antibody (MAB170, R&D system). This immunohistochemistry (IHC) stain result was interpreted by expert pathologists and then analyzed by image analysis software (Image-pro plus Ver 5.1). According to image analysis result of IHC stain, we divide patients into two groups as CXCR4 high and low expression. The results with age, tumor size, lymph node metastasis, estrogen receptor (ER), progesterone receptor (PR), and HER2/neu were examined by chi-square or Fisher’s exact test. Result: There is no significant difference between CXCR4 expression and pathological characteristics. But, there is significant difference between CXCR4 expression and lymph node metastasis in HER2/neu negative (p = 0.04) and hormone receptor positive patients (p = 0.02 in ER and p = 0.03 in PR). Conclusion: Our finding is that CXCR4 high expression contributes to axillary lymph node metastasis, especially when HER2/neu is negative. In other words, CXCR4 may be an alternative pathway in tumor invasion and metastasis when HER2/neu is not working. Another result is that CXCR4 high expression in hormone receptor positive patient associate with axillary lymph node metastasis. However, the really relationship between hormone receptor and CXCR4 is not quite clear and it needs further study. But, if CXCR4 really has influence on hormone receptor positive cancer cell, maybe that’s the reason why we use hormone therapy could achieve better outcome.
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Mathe, Andrea. "Genetic and epigenetic changes associated with the development of lymph node metastasis in triple negative breast cancer." Thesis, 2016. http://hdl.handle.net/1959.13/1314568.
Full textAbstract:
Research Doctorate - Doctor of Philosophy (PhD)Breast cancer is the most common cancer in women worldwide with one of the highest cancer-related death rates. The most aggressive breast cancer subtype is triple negative breast cancer (TNBC), which is characterised by the lack of expression for the estrogen receptor, progesterone receptor, and human epidermal growth factor 2. These receptors provide treatment targets in other breast cancer subtypes, which express at least one of these. Not only is there no targeted therapy for TNBC, it is also known to metastasise more frequently and earlier than other subtypes. Metastasis is the cause of most cancer-related deaths. This study aimed to identify genetic and epigenetic changes that are associated to lymph node metastasis in TNBC. In the first part of this study the gene expression of primary TNBC tumours (IDC), matched normal adjacent tissues (NAT) and matched lymph node metastases (LN) were examined using whole genome gene expression arrays. This revealed a novel four-gene signature specific for TNBC as well as an 83-gene signature associated with lymph node metastasis. Additionally, these findings were correlated with microRNAs that had previously been associated with lymph node metastasis in our own laboratory (using whole genome microRNA microarrays). microRNAs are small non-coding RNAs that are able to alter gene expression post-transcriptionally. After correlating genes and microRNAs that were associated with lymph node metastasis, the function of a number of these microRNAs were examined by overexpressing them in TNBC cells. Cell proliferation and migration were measured after transient microRNA mimic transfection. None of the tested microRNAs showed an effect on cell proliferation or migration, which may be due to the transfection method. Finally, the epigenetic mechanism of DNA methylation was investigated in these TNBC IDC, NAT and LN samples (using whole genome DNA methylation arrays). DNA methylation is the process whereby a methyl group is added to a cytosine base in the DNA, which leads to structural changes inhibiting gene transcription and therefore leads to gene silencing. The correlation of DNA methylation changes and gene expression changes provided novel insight into the development and progression of TNBC. Additionally, prognostic methylation changes were identified in this part of this study. Taken together, the results presented in this thesis show genetic (gene expression) and epigenetic (microRNAs and DNA methylation) changes that are associated with the development and progression of TNBC. This has not been done in TNBC on a whole genome level, including matched LN samples. This research has added to our knowledge and understanding of genetic and epigenetic changes that occur during the development and progression of TNBC. Especially, the novel insight in the progression of TNBC to secondary cancers provides potential prognostic indicators or therapeutic targets for this hard-to-treat subtype.
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Li, Karen Hui. "Micrometastatic node-positive breast cancer: an analysis of survival outcomes and prognostic impact of the number of positive nodes and the ratio of positive to excised nodes in comparison to node-negative and macrometastatic node-positive breast cancer." Thesis, 2009. http://hdl.handle.net/1828/1393.
Full textAbstract:
In this study, we examined survival for patients with micrometastases greater than 0.2mm but less than 2mm (pN1a) in comparison to node-negative (pN0) and macrometastatic node-positive (pN1b) patients. Data for patients diagnosed from 1988 to 1998 with TNM pathological T1-2 stage, pN0, and pN1a-b breast cancer with no distant metastasis was provided by Dr. P. Truong from BC Cancer Agency. Results obtained from the Kaplan-Meier estimators and the multivariable Cox Proportional Hazards Model analyses suggested that micrometastatic node-positive patients had worse survival than the node-negative patients, but better survival in comparison to the macrometastatic node-positive patients. Increasing number of positive nodes and larger values of the ratio of positive to excised nodes were significantly associated with worse survival.
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Murch, Lisa Elaine. "Evaluation of pathologic parameters and published nomograms in predicting non-sentinel lymph node metastases in female breast cancer patients with positive sentinel lymph nodes." 2007. http://hdl.handle.net/1993/21219.
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Klein, Evelyn [Verfasser]. "Evaluation of side effects after axillary lymph node dissection for breast cancer taking tumour staging status into account / Evelyn Klein." 2009. http://d-nb.info/1006965459/34.
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Rempp, Hansjörg [Verfasser]. "Sentinel lymph-node radiodetection in breast cancer : results of a clinical study and development of a quantitative approach / vorgelegt von Hansjörg Rempp." 2005. http://d-nb.info/977655350/34.
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Chu, Hou-Wei, and 禇候維. "A Novel Estrogen Receptor-microRNA 190a-PAR-1-Pathway Regulates Breast Cancer Progression, A Finding Initially Suggested by Genome-Wide Analysis of Loci Associated with Lymph-Node Metastasis." Thesis, 2013. http://ndltd.ncl.edu.tw/handle/45156246177806729968.
Full textAbstract:
博士國防醫學院
生命科學研究所
102
To identify microRNAs that are important in regulating breast cancer progression, the present study used data for the 199961 single-nucleotide polymorphisms (SNPs) in 837 breast cancer patients genotyped in a recent genome-wide association study to identify loci associated with lymph node metastasis (LNM). SNPs tagging the 15q22.2 locus showed a significant association with LNM and miR-190a was found to be the only microRNA in this region. The role of miR-190a in LNM was supported by the findings that increased miR-190a expression inhibited cell migration and invasiveness and that the target of miR-190a was protease-activated-receptor 1 (PAR-1), which is a metastasis promoting protein in several cancers. In addition, the promoter region of miR-190a was defined and found to contain half of an estrogen response element, suggesting that miR-190a is regulated by estrogen receptor (ER) signaling. This was confirmed by the findings that miR-190a expression was activated by 17β-estradiol and that ERα bound directly to this promoter. The importance of this ERα-miR190a-PAR-1 link in breast tumorigenesis is suggested by the findings of (a) an association between genetic polymorphism of the miR-190a-containing region and LNM that is modified by SNPs of PAR-1 and is particularly significant in ERα-positive patients and (b) a combined effect of ERα and miR-190a expression on tumor grade/cancer stage. More importantly, the level of miR-190a expression in primary breast carcinomas correlated with overall survival. These findings suggest a novel pathway in which ERα signaling regulates miR-190a expression, causing inhibition of PAR-1 expression, correlated with inhibition of cancer metastasis.
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Kolařík, Dušan. "Populace buněk karcinomu prsu. Využití pro stanovení optimálního terapeutického postupu. Prediktivní model." Doctoral thesis, 2016. http://www.nusl.cz/ntk/nusl-351520.
Full textAbstract:
1 ABSTRACT Background Breast cancer cell population characteristics are used in common clinical practice for estimation of prognosis of the malignant disease (prognostic factors) and for prediction of reactivity of the tumor to certain therapeutic modality (predictive factors). Also axillary lymph node status is an independent prognostic factor in women with early breast cancer. Therefore, surgical excision and following histopathological examination of the nodes is the obligatory part of primary breast cancer surgery. The extension of axillary surgery varies widely, although sentinel lymph node biopsy is considered to be the standard procedure. However, it must be admitted that this type of procedure need not be optimal for all the breast cancer patients. Aims of the study The aim of this study is the verify the hypothesis whether or not the axillary lymph node metastatic affection can be effectively estimated using non-surgical methods - i.e. by evaluation of the combination of prognostic and predictive factors of the primary breast tumor. Statistical model composed on the basis of data of early breast cancer patients is the basic tool for this prediction. Application of this model In everyday practice can enable to adjust the extent of axillary surgery for each individual patient. Patients and methods A...
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Dostálek, Lukáš. "Možnosti značení lymfatických uzlin v axile u pacientek s karcinomem prsu." Doctoral thesis, 2021. http://www.nusl.cz/ntk/nusl-446960.
Full textAbstract:
Introduction Axillary dissection has little diagnostic and therapeutic benefit in the node-positive breast cancer patients in whom axillary disease has been completely eradicated after neoadjuvant chemotherapy (ypN0). We sought to assess the efficacy of an algorithm used for the identification of the ypN0 patients consisting of intraoperative evaluation of sentinel and tattooed (initially positive) lymph nodes. Methods Included were T1 and T2 breast cancer patients with one to three positive axillary lymph nodes marked with carbon who were referred for neoadjuvant chemotherapy followed by a surgery. Axillary dissection was performed only in the patients with residual axillary disease after neoadjuvant chemotherapy on ultrasound or with metastases described in the sentinel or tattooed lymph nodes either intraoperatively or in the final histology. Results Out of 62 included initially node-positive patients, 15 (24%) were spared axillary dissection. The detection rate of tattooed lymph node after neoadjuvant chemotherapy was 81%. The ypN0 patients were identified with 91% sensitivity and 38% specificity using ultrasound and intraoperative assessment of both sentinel and tattooed lymph node according to the final histology. Discussion/Conclusion Lymph node marking with carbon dye is a useful and...
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Duarte, Nuno Miguel de Faria Bento. "Fisioterapia: influência na qualidade de vida da mulher com cancro da mama: contributo para a qualidade do serviço em oncologia." Doctoral thesis, 2016. http://hdl.handle.net/10362/20113.
Full textAbstract:
RESUMO - Introdução: As modalidades da cirurgia a cancro da mama que recorrem apenas à
biópsia do gânglio sentinela (BGS) têm um menor impacto na qualidade de vida (QdV)
das mulheres quando comparadas às cirurgias em que é realizada uma linfadenectomia
axilar. No entanto, na fase aguda de sobrevivência, na qual são realizados tratamentos
por terapias oncológicas ao longo do primeiro ano após o diagnóstico, o efeito dessas
terapias poderá sobrepor-se à menor agressividade da cirurgia com BGS, levando a que
não existam diferenças na QdV destes dois grupos de doentes. Existe alguma evidência
de que a fisioterapia pode contribuir para a melhoria da QdV das doentes com cancro
da mama, todavia as doentes submetidas a cirurgia com BGS raramente são incluídas
num programa de reabilitação funcional pelo facto de estar associada a ideia que nesta
cirurgia existe uma ausência de morbilidade. Torna-se relevante que seja esclarecido
se a fisioterapia contribui para a melhoria da QdV da mulher com cancro da mama
submetida a cirurgia com BGS, tentando, desta forma, esclarecer se a fisioterapia pode
contribuir para a qualidade de serviço prestado a esse grupo de doentes.
Materiais e Métodos: Foi desenvolvido um estudo Quasi-experimental. A amostra do
estudo foi constituída por um grupo de 172 mulheres com cancro da mama submetidas
a cirurgia com BGS e a outras terapias oncológicas. Das 172 doentes, 90 foram
incluídas no grupo de controlo e 82 no grupo experimental. Utilizou-se o questionário
EORTC C30 e o EORTC BR23 para a recolha de dados sobre a QdV ao longo dos
primeiros 9 meses pós-cirurgia (1, 3, 6 e 9 meses). O grupo experimental foi submetido
a técnicas específicas de fisioterapia na reabilitação funcional da mulher com cancro da
mama enquanto o grupo de controlo foi apenas alvo de avaliações. Utilizou-se a
estatística descritiva bivariável para a caracterização da amostra, recorrendo-se à
estatística inferencial para analisar as questões de investigação. A regressão de
Poisson foi utilizada para realizar o cálculo do Benefício Relativo (BRa) e Risco Relativo
(RRa) ajustados para diversos fatores de confundimento na baseline do estudo. O nível
de significância utilizado no estudo foi de 5% e os intervalos de confiança (IC) foram
estabelecidos em 95%. Todos os cálculos foram efetuados com recurso ao software
SPSS, versão 20, com exceção do cálculo do BR e do RR e respetivos IC a 95% da
análise bivariável, em que foi utilizado o programa online OpenEpi versão 3.
Resultados: Ao 3º mês pós-cirurgia o grupo experimental apresentou maior proporção
de doentes com uma melhoria clínica relevante no Estado de Saúde Global (ESG)
(BRa=2,230; p=0,014) e um menor risco de degradação do ESG (RRa=0,384; p=0,011),
Função Física (FF) (RRa=0,484; p=0,035) e Sintomas Membro Superior (SMS)
(RRa=0,159; p=0,007), quando comparado ao grupo de controlo. Entre o 1º e 6º mês
pós-cirurgia a fisioterapia parece atuar como um fator protetor na degradação do ESG
e FF. Entre o 1º e 9º mês pós-cirurgia o grupo experimental apresentou maior proporção
de doentes com melhoria clínica relevante, estatisticamente significativa, no ESG
(BRa=1,905; p=0,038) e nos SMS (BRa=1,761; p=0,029) e um menor risco de
degradação nas escalas de ESG (RRa=0,287; p=0,010) e SMS (RRa=0,265; p=0,0421),
quando comparado ao grupo de controlo.
Conclusão: Podemos concluir que a fisioterapia pode contribuir para a melhoria da QdV
das mulheres com cancro de mama submetidas a cirurgias com BGS, no decorrer da
fase aguda de sobrevivência, podendo dar um contributo favorável para a qualidade do
serviço prestado a este grupo de doentes.ABSTRACT - Introduction: The surgical modalities for breast cancer which use only sentinel lymph node biopsy (SLNB) have a lesser impact in quality of life (QoL) of women when compared to surgeries in which an axillary lymph node dissection is performed. However, in the acute phase of survival, in which treatments by oncologic therapies are performed during the first year after the diagnosis, the effect of these therapies can superimpose the less aggressive surgery with SLNB, leading to no differences in QoL of these two groups of patients. There is some evidence that physical therapy can help improve the QoL of patients with breast cancer, nevertheless the patients undergoing surgery with SLNB are rarely included in functional rehabilitation programs due to the idea that in this surgery there is an absence of morbidity. It is relevant to clarify whether physiotherapy contributes to improve the QoL of women with breast cancer who underwent surgery with SNLB. Trying, this way, to understand if physical therapy can contribute to the quality of service provided to this group of patients. Materials and Methods: We have developed a Quasi-experimental study. The study sample was composed by a group of 172 women with breast cancer who underwent surgery with SNLB and other oncologic therapies. Of the 172 patients, 90 were included in the control group and 82 in the experimental group. We used the EORTC C30 and EORTC BR23 questionnaires to collect data about the QoL in the course of the first 9 months after surgery (1, 3, 6 and 9 months). The experimental group was subjected to specific physical therapy techniques in functional rehabilitation of women with breast cancer while the control group was only the target of assessments. We used bivariate descriptive statistics for sample characterisation, resorting to inferential statistics to analyse the research questions. Poisson regression was used to perform the calculation of the Relative Benefit (aRB) and Relative Risk (aRR) adjusted for several confounding factors at baseline of the study. The significance level used in the study was 5% and the confidence interval (CI) was established at 95%. All calculations were performed using the SPSS software, 20th version, with the exception of the calculation of the RB and RR and respective CI at 95% of the bivariate analysis, for which we used the online program OpenEpi 3rd version. Results: On the 3rd month after surgery the experimental group showed a higher proportion of patients with a relevant clinical improvement in the Global Health Status (GHS) (aRB=2,230; p=0,014) and a lower risk of degradation of the GHS (aRR=0,384; p=0,011), Physical Function (PF) (aRR=0,484; p=0,035) and Upper Limb Symptoms (ULS) (aRR=0,159; p=0,007), when compared to the control group. Between the 1st and 6th month after surgery, physical therapy seems to act as a protective factor on the degradation of GHS and PF. Between the 1st and 9th month after surgery the experimental group showed a higher proportion of patients with relevant clinical improvement, statistically significant, in the GHS (aRB=1,905; p=0,038) and in the ULS (aRB=1,761; p=0,029) and a lower risk of degradation of the GHS (aRR=0,287; p=0,010) and ULS (aRR=0,265; p=0,0421) scales, when compared to the control group. Conclusion: It can be concluded that physiotherapy can contribute to improve the QoL of women with breast cancer who underwent surgeries with SNLB, in the course of the acute phase of survival, giving a favourable contribution to the quality of service provided to this group of patients.
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Mechtouf, Nawel. "Détection moléculaire des métastases des ganglions lymphatique dans le cancer du col de l'utérus." Thèse, 2014. http://hdl.handle.net/1866/12768.
Full textAbstract:
Le Cancer du Col Utérin (CCU) chez la femme est provoqué par le virus oncogénique VPH. La métastase lymphatique ganglionnaire est un facteur pronostique majeur pour l’évolution de ce cancer et sa présence influence la décision thérapeutique. En général, l’envahissement ganglionnaire est diagnostiqué par histologie, mais cette méthode est laborieuse et parfois prise en défaut pour détecter les micrométastases et les cellules cancéreuses isolées et pour donner des résultats rapides en per opératoire. L’outil moléculaire que nous désirons développer pour combler cette lacune est basé sur une analyse d’ARN des gènes du VPH exprimés par les cellules du CCU. Ceci sera fait par transcription réverse de l’ARN cellulaire couplé à une réaction quantitative en chaine par polymérase en temps réel (RT-qPCR). Cette technique devrait nous permettre une détection et une évaluation rapide des micrométastases pour aider à déterminer immédiatement un pronostic fiable et la thérapie associée. C’est un test précis, sensible et rapide pour détecter un envahissement ganglionnaire dans le CCU visant à améliorer la gestion thérapeutique. Le projet est basé sur trois objectifs. En premier lieu, valider les marqueurs moléculaires E6 et E7 de VPH16 et 18 à partir des échantillons frais et des échantillons fixés dans des blocs de paraffine. En deuxième lieu, déterminer la fiabilité et la sensibilité des marqueurs pour la détection des macrométastases, des micrométastases et les cellules tumorales isolées en utilisant la technique de RT-qPCR. En troisième lieu et parallèlement au travail présenté dans ce mémoire, il est nécessaire de constituer une base de données des patientes qui ont le virus VPH16 et 18 intégré dans leur génome, qui ont été traitées et dont nous connaissons déjà le diagnostic final afin de valider la méthode (biobanque). Nous avons réussi à extraire de l’ARNm de haute qualité à partir d’échantillons complexes, à détecter les gènes E6 et E7 de VPH16 et 18 en RT-qPCR, et à déterminer précisément la limite de détection de E6 et E7 dans les échantillons frais qui est une proportion de 0,008% de cellules cancéreuses. Dans les échantillons fixés dans la paraffine, cette limite est de 0,02% et 0,05% pour E6-E7-VPH16 et E6-E7-VPH18 respectivement. Ceci comparativement à une limite de détection histologique de 1% qui est déterminée par immunohistochimie de CK19. Enfin, notre protocole est validé pour VPH18 dans les ganglions lymphatiques du CCU.The presence of lymph nodes metastasis in uterine cervical carcinoma influences therapeutic management and patient survival. The gold standard for metastasis detection is histology. However, histology lacks sensitivity to detect micrometastasis or isolated cancer cells and is not an efficient method for immediate diagnosis during surgery. The molecular tool that we want to develop to fill this gap is based on an analysis of expressed RNA transcripts derived from the HPV genome in cells of uterine cervical carcinoma (UCC). This will be done by reverse transcription of cellular RNA coupled to a quantitative polymerase chain reaction in real-time (RT-qPCR). This technique could allow detection and rapid assessment of micrometastasis to help determine prognosis and an immediate reliable combination therapy. The proposed technique would be a specific test, sensitive and rapid to detect lymph node involvement in the UCC to improve therapy management. Our objective is to constitute a patient bank containing genetic and clinical information. This genetic information will be used to test and improve new molecular markers for UCC metastasis. These markers will be validated using comparisons to traditional histological results and evaluated for their capacity to detect lymph nodes micrometastasis. Ultimately, we wish to develop a reliable molecular diagnosis method useful during surgery and improve our knowledge about the clinical evolution of metastatic UCC. Currently, we are able to extract high quality mRNA from formalin-fixed cells mounted in paraffin blocks and to detect E6 and E7 from HPV16 and HPV18 using RT-qPCR. We have specifically determined the detection limit of E6 and E7, which is 0.008% in the fresh samples and 0.02% and 0.05% for HPV16-E6-E7 and HPV18- E6-E7 respectively in the samples fixed in paraffin blocks. Comparatively, the histological detection limit was determined to be around 1% using immunohistochemistry for CK19 expression. Finally, our protocol has been validated for HPV18 in UCC patient lymph nodes
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Hashim, Che Gon. "Identifying predictors of postoperative persistent pain in women with breast cancer: assessments of investigative tools." Master's thesis, 2018. http://hdl.handle.net/1885/162744.
Full textAbstract:
Persistent pain after surgery in breast cancer has a significant
impact on the patient’s survival. The value of escalating
research on breast cancer in Malaysia cannot be underestimated.
However, it is not known how many of these women experience
persistent pain after surgery. This study surveyed previously
unknown figures on prevalence, and explored the predictive
factors of persistent pain women with breast cancer in Malaysia.
There were three objectives. First, to assess the reliability of
the already established investigative tools, namely, the Brief
Pain Inventory, Distress Thermometer, and Resilience scale RS-14;
second, to survey the prevalence of persistent pain; and thirdly
to identify predictors of persistent pain in women after breast
surgery, using the above measures. A test and retest design with
no intervention and a recall period of 3 to 7 days was employed
for assessment of the investigative tools. A cross-sectional
study, with a prospective, correlational design, a retrospective
review of medical records was used to identify predictors of
persistent pain. These investigations were conducted in two
phases –Section A and Section B – using separate data sets,
with different inclusion and exclusion criteria. Participants
were recruited from the University of Malaya Medical Centre,
Malaysia. Descriptive statistics, a stepwise regression model for
reliability testing, Cronbach alpha, and factor analysis were
used. This study divided pain into categories 0 = no pain, 1–4
= mild pain, 5–6 = moderate pain, and 7–10 = severe pain.
Section A: The tools were found reliable. Section B: A total of
123 participants were recruited; 119 participants remained
because 4 of them did not meet the inclusion criteria. A total of
43% of the participants had persistent pain (n = 51). Pain
interfered with their work, mood, and sleep. Based on a “Yes”
answer for pain today (n = 51), data were analysed to determine
predictors. The results revealed three predictors: distress, B =
–.911, resilience, B = –.444, and pain interference, B =
.309. The model was statistically significant, F (3, 41, 44) =
13.827, R2 = 0.267, .381, .467), and adjusted R2 = .250, .351,
.467, p = 0.001. Significant P value ≤ .005. Pain prevalence
was 43% in this Malaysian population. This study provided
empirical evidence which is an important new knowledge to health
care systems, health care providers, policy makers, and future
research. The impact of persistent pain on work, mood, and sleep
are justifiable medical concerns. The results obtained and
identified predictors are catalysts for providing extra support
for breast cancer women after surgery. Ideally, all women with
breast cancer should have very good life satisfaction.
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Kocián, Roman. "Význam biopsie sentinelové uzliny v léčbě pacientek s časným stádiem karcinomu děložního hrdla." Doctoral thesis, 2021. http://www.nusl.cz/ntk/nusl-447348.
Full textAbstract:
The sentinel lymph node biopsy is part of recommended surgical staging guidelines in patients with early stages of cervical cancer. High success rates of bilateral detection of SLN are achieved in sites with adequate experience with this procedure. The sentinel lymph node biopsy without systematic pelvic lymph node dissection is currently considered inadequate procedure for stages IB to IIA of the disease. One of the benefits of sentinel lymph node detection is extensive histopathological examination using the ultrastaging protocol enabling detection of small metastases (i.e. micrometastases). At the moment, there is lack of evidence about oncological safety of sentinel lymph node biopsy which might replace systematic lymph node dissection in the future. Prognostic significance of micrometastases is also controversial due to the lack of data about their potential presence in non-sentinel lymph nodes in cases with negative sentinel lymph nodes. This dissertation deals with the concept of sentinel lymph node biopsy in the cervical cancer and focuses on several topics. We have shown that the presence of micrometastasis is associated with significant negative impact on patients' prognosis on the largest retrospective cohort of patients ever published. Only 67% of patients with micrometastasis have...