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The role of HER4 in relation to trastuzumab resistance and prognosis in HER2 positive breast cancerMohd Nafi, Siti Norasikin January 2014 (has links)
Background Trastuzumab resistance imposes a major limitation to the successful treatment of HER2 positive breast cancer. The expression of HER4 and its prognostic value is controversial in breast cancer. Furthermore, its role in trastuzumab treatment and resistance in HER2 positive breast cancer has not been reported. Methods The effects of trastuzumab on HER4 cleavage and its localisation were studied in both parental and trastuzumab-resistant SKBR3 and BT474 cells using western blot, RT-PCR, nuclear fractionation and confocal microscopy. Tissue microarrays consisting of a cohort of HER2 positive breast cancer patients were stained for HER4 by immunohistochemistry and the results were correlated with patients’ outcome. This study also assessed HER4 expression in the tumor samples from a window study of trastuzumab alone or in combination with neoadjuvant chemotherapy in HER2 positive breast cancer patients. Results Trastuzumab treatment upregulated HER4 mRNA, and increased expression of both 80 and 180 kDa HER4 protein isoforms, and induced nuclear translocation of 80kDa HER4 protein isoforms, which the results similar to heregulin stimulation. This was also seen in trastuzumab resistant cells although HER4<sub>80kDa</sub> and nuclear HER4 decreased upon overnight withdrawal of trastuzumab in resistant cell lines. In addition, knockdown of HER4 protein expression by specific siRNAs increased trastuzumab sensitivity and reversed trastuzumab resistance in SKBR3 and BT474 cells, confirming the importance of HER4 in trastuzumab response. This study also showed that trastuzumab-induced HER4 nuclear translocation is due to HER4 activation and cleavage since γ-secretase inhibitor (GSi) and neratinib prevented the process when combined with trastuzumab treatment, correlating with an increased apoptosis and decreased cell viability. There was also increased nuclear HER4 expression in tumors from both BT474 xenografts and from patients with breast cancer treated with trastuzumab monotherapy. Furthermore, nuclear HER4 predicted poor clinical response to trastuzumab monotherapy in patients undergoing a window study and was a poor prognostic factor in HER2 positive breast cancer. Conclusions This study suggests HER4 activation, cleavage and nuclear translocation play a key role in trastuzumab resistance in HER2 positive breast cancer. Nuclear HER4 could be a novel predictive and prognostic biomarker in HER2 positive breast cancer patients.
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The contribution of molecular imaging to early evaluation of response to anti-HER2 agents in Breast CancerGebhart, Géraldine 08 June 2016 (has links)
L’imagerie en oncologie a fait des progrès considérables ces dernières années avec l’introduction du CT scan spiralé, de la résonance magnétique, de la mammographie digitalisée et du PET scan. Des combinaisons de différentes techniques ont vu le jour, telles que le PET/CT, et améliorent encore les possibilités de stadification de la maladie cancéreuse ainsi que le monitoring de son évolution dans le temps, et notamment sous traitement.Parallèlement, de grands progrès thérapeutiques ont étés réalisés en oncologie, en particulier le développement de médicaments « ciblés » dont l’efficacité dépend de l’expression par la cellule tumorale d’une molécule cible jouant un rôle important dans sa survie et/ou sa prolifération. L’expression de la molécule cible est une condition nécessaire mais pas suffisante pour observer une réponse au traitement ciblé :l’échec de ce dernier peut aussi s’expliquer par des altérations moléculaires en amont ou en aval de la « cible ».Le cancer du sein dit « HER2 positif » représente 20 à 25% des cancers du sein. Celui-ci est caractérisé par l’expression membranaire, en quantités importantes, d’une protéine, appelée HER2, qui lui confère une biologie agressive et un mauvais pronostic. L’expression de HER2 au niveau de la tumeur, déterminée en routine clinique par immunohistochimie et/ou par hybridation in situ en fluorescence, est le seul biomarqueur validé aujourd’hui dans le cancer du sein HER2 positif pour prédire l’efficacité des traitements ciblés anti-HER2. Cette prédiction est toutefois peu satisfaisante en termes de valeur prédictive positive (50% environ). Après une revue de la litérature sur les études d’imagerie fonctionnelle, peu nombreuses, réalisées dans le cancer du sein HER2 positif, nous avons décidé d’explorer le rôle de l’imagerie moléculaire avec la technologie PET/CT dans l’individualisation de la prise en charge du cancer du sein HER2 positif avec deux radio traceurs (FDG et zirconium89-trastuzumab), et ce, dans deux contextes cliniques distincts :dans la maladie précoce soumise à un traitement neoadjuvant et dans le contexte métastatique, en cas de traitement par le T-DM1. / Doctorat en Sciences médicales (Médecine) / info:eu-repo/semantics/nonPublished
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Long-Time Response With Ado-Trastuzumab Emtansine in a Recurrent Metastatic Breast CancerManthri, Sukesh, Singal, Sakshi, Youssef, Bahaaeldin, Chakraborty, Kanishka 30 October 2019 (has links)
Breast cancer is the most common cancer in a woman with a five-year survival of patients with metastatic disease is estimated at 23%. Ado-trastuzumab emtansine (T-DM1) is a HER2-antibody drug conjugate currently approved for the treatment of HER2-positive pre-treated metastatic breast cancer (BC). We report a case of recurrent metastatic breast cancer with unusually lengthy progression-free survival (PFS) on T-DM1 chemotherapy. She was diagnosed with Triple Positive Stage IIIC multifocal invasive ductal carcinoma of the left breast. After completing neoadjuvant chemotherapy, she underwent a bilateral mastectomy. Final pathology showed partial response. Postoperatively, she received adjuvant chemotherapy and radiation therapy. She was started on Q21 days trastuzumab following completion of adjuvant chemotherapy. Systemic imaging showed liver lesions and biopsy confirmed recurrence. She was started on T-DM1, endocrine therapy with anastrozole was continued. She is currently status post 45 cycles. T-DM1 was approved for the treatment (single-agent) of HER2-positive, metastatic BC based on phase III data from the EMILIA and TH3RESA study. Median PFS in the T-DM1 arm was 9.6 months. Herein, we present a case of a woman with recurrent triple positive metastatic BC with a lengthy progression-free survival on T-DM1 chemotherapy.
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Uso de trastuzumabe para o tratamento de mulheres com câncer de mama HER2 positivo: um estudo farmacoepidemiológico / Trastuzumab use for the treatment of women with HER2-positive breast cancer: a pharmacoepidemiological studyAyres, Lorena Rocha 24 March 2015 (has links)
Introdução: O câncer de mama é o segundo tipo de câncer mais frequente no mundo, com cerca de 1,67 milhões de casos novos e 521 mil mortes a cada ano. O câncer de mama pode ser classificado em diferentes grupos, sendo o subtipo HER2 positivo um dos mais agressivos e relacionado a um mal prognóstico. No entanto novas terapias, tendo como alvo o receptor HER2, vem sendo desenvolvidas com a finalidade de melhorar as condições das pacientes. Dentre elas encontra-se o trastuzumabe, um anticorpo monoclonal recombinante humanizado do tipo IgG1, o qual se liga com alta afinidade ao domínio extracelular do receptor HER2. O uso do trastuzumabe está associado a um aumento da taxa de sobrevida de mulheres com câncer de mama HER2 positivo. O trastuzumabe é geralmente bem tolerado, porém pode apresentar alguns eventos adversos dentre eles, a cardiotoxicidade, a qual pode levar à interrupção do tratamento, fazendo com que as pacientes se privem dos benefícios desta terapia medicamentosa. Além desse efeito, outros podem afetar a satisfação da paciente tais como as reações imunes relacionadas à infusão do trastuzumabe, eventos gastrointestinais, fadiga, dentre outros. Com a finalidade de aprimorar os cuidados à saúde, faz-se necessário avaliar os eventos adversos ao tratamento, bem como a qualidade de vida (QV) das mulheres com câncer de mama HER2 positivo que fazem uso do trastuzumabe visando contribuir para o aumento do seu bem-estar e garantir melhores resultados terapêuticos. Objetivo: Avaliar o perfil farmacoepidemiológico das mulheres com câncer de mama HER2 positivo que utilizaram o trastuzumabe atendidas pelo Sistema Único de Saúde, junto ao Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo. Casuística e métodos: O presente trabalho é um estudo observacional, descritivo e quantitativo, o qual foi realizado em duas partes. Parte A: restrospectiva, na qual se avaliou os eventos adversos ao trastuzumabe em monoterapia e/ou combinado com a quimioterapia descritos nos prontuários e por meio de exames laboratoriais e dos resultados do ecocardiograma. Foram utilizados modelos de regressão logística para estimar odds ratios e seus respectivos intervalos de confiança de 95%, com a finalidade de verificar a associação dos eventos adversos mais frequentes e uma série de variáveis sociodemográficas e clínicas das mulheres. Parte B: prospectiva, na qual, além da avaliação dos eventos adversos, foi também avaliada a QV das pacientes por meio do questionário específico para câncer QLQ-C30 e seu módulo de câncer de mama BR-23 da European Organization for Research and Treatment of Cancer (EORTC) em quatro momentos: antes do início da quimioterapia, após o término da quimioterapia, durante o uso do trastuzumabe e após o término do uso trastuzumabe. Análise de variância (ANOVA) para medidas repetidas foi utilizada para as comparações entre os escores médios obtidos das escalas e itens individuais dos questionários. Resultados Parte A: Foram analisados os prontuários de 79 pacientes que iniciaram o trastuzumabe entre 2007 e 2011. A incidência de reações imunes relacionadas a infusão do trastuzumabe aconteceu em 16 (20,3%) pacientes. A cardiotoxicidade ocorreu em 26 (32,9%) pacientes, sendo que treze (16,4%) destas interromperam permanentemente o tratamento, três (3,8%) interromperam temporariamente e 10 xi (12,6%) terminaram o tratamento sem interrupção. Com relação aos outros eventos adversos, os mais frequentes apresentados com o uso da quimioterapia combinada com o trastuzumabe foram dor (20,4%), náusea e vômito (15,9%), febre (9,7%), e neutropenia (7,1%), sendo apresentados por 55,7% das mulheres. Com relação ao uso do trastuzumabe em monoterapia, os mais frequentes foram: dor (19,6%), fadiga (10,8%), náusea e vômito (9,8%), e cefaleia (8,8%) apresentados por 49,4% das mulheres. Com exceção da cardiotoxicidade, nenhum outro evento adverso levou à descontinuação do tratamento. Não foram encontradas associações entre os eventos adversos mais frequentes e as variáveis sociodemográficas e clínicas das pacientes pelos modelos de regressão logística. Resultados Parte B: Dez pacientes foram incluídas no estudo, no período de outubro de 2011 a julho de 2012. Durante o uso do trastuzumabe e após o seu término foi observada uma melhora significativa da QV das pacientes nos parâmetros fadiga e efeitos colaterais sistêmicos, em comparação com o momento em que estavam utilizando os quimioterápicos. Entretanto estudos mais extensos com uma maior população são necessários para que possa ser avaliada a existência de associação entre os dados clínicos e sociodemográficos das pacientes como os resultados de QV. Conclusão: Embora o trastuzumabe seja um medicamento relativamente seguro para o tratamento do câncer de mama HER2 positivo, este pode causas alguns eventos adversos. Na população estudada, o único evento que levou à interrupção do tratamento foi a cardiotoxicidade, entretanto outros estudos mostraram que outros eventos adversos também foram capazes de ocasionar a descontinuação do tratamento. Para tanto são necessários que sejam tomados alguns cuidados para a prevenção e manejo desses eventos adversos, como um acompanhamento mais regular da função cardíaca e monitoramento constante das pacientes durante a infusão do trastuzumabe. Além disso, o trastuzumabe mostrou ter efeito positivo sobre a QV das pacientes. A avaliação da QV é importante, pois fornece informações clínica úteis em relação ao real impacto do tratamento proposto sobre a saúde e bem-estar das pacientes e pode também orientar na busca de estratégicas para minimizar os eventos adversos ao tratamento. / Introduction: Breast cancer is the second most common cancer in the world, with about 1.67 million new cases and 521,000 deaths each year. Breast cancer can be classified into different groups, being the HER2 positive subtype one of the most aggressive and related to a poor prognosis. However, new therapies that target the HER2 receptor have been developed in order to improve the conditions of patients. Among them is trastuzumab, a recombinant humanized monoclonal antibody of the IgG1 type, which binds with high affinity to the extracellular domain of the HER2 receptor. The use of trastuzumab is associated with an increase in the survival rate of women with HER2 positive breast cancer. Trastuzumab is generally well tolerated, but may have some adverse events, among them the cardiotoxicity, which can lead to treatment discontinuation, depriving patients of the benefits of this therapy. In addition to this effect, others may affect patient satisfaction such as immune reactions related to the infusion of trastuzumab, gastrointestinal events, fatigue, among others. In order to improve health care, it is necessary to assess treatment adverse events and quality of life (QoL) of women with HER2-positive breast cancer that uses trastuzumab to contribute to the increase in their welfare and ensure better treatment results. Objective: To evaluate the pharmacoepidemiological profile of women with HER2-positive breast cancer that used trastuzumab attended by Brazilian public health system, in the General Hospital of Ribeirão Preto Medical School, University of São Paulo. Patients and methods: This is an observational, descriptive and quantitative study, which was conducted in two parts. Part A: retrospective, in which it was evaluated the adverse events to trastuzumab alone and / or combined with chemotherapy described in the medical records and by laboratory tests and echocardiogram results. We used logistic regression models to estimate odds ratios and their 95% confidence intervals to verify the association of the most frequent adverse events and a number of sociodemographic and clinical variables. Part B: prospective, in which besides the evaluation of adverse events it was also evaluated the QoL of patients through the specific questionnaire QLQ-C30 cancer and its breast cancer module BR-23 from the European Organization for Research and Treatment of Cancer (EORTC) in four moments: before the start of chemotherapy, after the end of chemotherapy, during the use of trastuzumab and after the trastuzumab use. Results Part A: The medical records of 79 patients who started the trastuzumab between 2007 and 2011 were analysed. The incidence of immune reactions related to the infusion of trastuzumab occurred in 16 (20.3%) patients. Cardiotoxicity occurred in 26 (32.9%) patients, and 13 (16.4%) of these permanently discontinued the treatment, three (3.8%) discontinued temporarily and 10 (12.6%) completed treatment without interruption. In relation to the other adverse events, the most common events described with the use of trastuzumab combined with chemotherapy were pain (20.4%), nausea and vomiting (15.9%), fever (9.7%), and neutropenia (7.1%), being presented by 55.7% of women. Regarding the use of trastuzumab in monotherapy, the most common were pain (19.6%), fatigue (10.8%), nausea and vomiting (9.8%) and headache (8.8%) presented by 49.4% of women. Except for cardiotoxicity, no other adverse events led to treatment discontinuation. xiii No associations were found between the most frequent adverse events and the sociodemographic and clinical variables of the patients by logistic regression models. Results Part B: Ten patients were included in the study from October 2011 to July 2012. During the use of trastuzumab and after its completion, a significant improvement in QoL of patients on the parameters fatigue and systemic side effects were observed in comparison with the moment they were using chemotherapy. Nevertheless, larger studies with a larger population are needed in order to evaluate if there is an association between clinical and social demographic data of the patients with the results of QoL. Conclusion: Although trastuzumab is a relatively safe medication for the treatment of HER2 positive breast cancer, it may cause some adverse events. In this population, the only event that led to treatment interruption was cardiotoxicity, although other studies have shown that other adverse events were also able to cause treatment discontinuation. Therefore, some precaution needs to be taken for the prevention and management of those adverse events, such as a more regular monitoring of cardiac function and constant monitoring of patients during trastuzumab infusion. Furthermore, trastuzumab has shown to have a positive effect on patients QoL. The assessment of QoL is important as it provides useful clinical information regarding the real impact of the proposed treatment on the health and welfare of patients and can also guide the search for strategies to minimize treatment adverse events.
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Uso de trastuzumabe para o tratamento de mulheres com câncer de mama HER2 positivo: um estudo farmacoepidemiológico / Trastuzumab use for the treatment of women with HER2-positive breast cancer: a pharmacoepidemiological studyLorena Rocha Ayres 24 March 2015 (has links)
Introdução: O câncer de mama é o segundo tipo de câncer mais frequente no mundo, com cerca de 1,67 milhões de casos novos e 521 mil mortes a cada ano. O câncer de mama pode ser classificado em diferentes grupos, sendo o subtipo HER2 positivo um dos mais agressivos e relacionado a um mal prognóstico. No entanto novas terapias, tendo como alvo o receptor HER2, vem sendo desenvolvidas com a finalidade de melhorar as condições das pacientes. Dentre elas encontra-se o trastuzumabe, um anticorpo monoclonal recombinante humanizado do tipo IgG1, o qual se liga com alta afinidade ao domínio extracelular do receptor HER2. O uso do trastuzumabe está associado a um aumento da taxa de sobrevida de mulheres com câncer de mama HER2 positivo. O trastuzumabe é geralmente bem tolerado, porém pode apresentar alguns eventos adversos dentre eles, a cardiotoxicidade, a qual pode levar à interrupção do tratamento, fazendo com que as pacientes se privem dos benefícios desta terapia medicamentosa. Além desse efeito, outros podem afetar a satisfação da paciente tais como as reações imunes relacionadas à infusão do trastuzumabe, eventos gastrointestinais, fadiga, dentre outros. Com a finalidade de aprimorar os cuidados à saúde, faz-se necessário avaliar os eventos adversos ao tratamento, bem como a qualidade de vida (QV) das mulheres com câncer de mama HER2 positivo que fazem uso do trastuzumabe visando contribuir para o aumento do seu bem-estar e garantir melhores resultados terapêuticos. Objetivo: Avaliar o perfil farmacoepidemiológico das mulheres com câncer de mama HER2 positivo que utilizaram o trastuzumabe atendidas pelo Sistema Único de Saúde, junto ao Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo. Casuística e métodos: O presente trabalho é um estudo observacional, descritivo e quantitativo, o qual foi realizado em duas partes. Parte A: restrospectiva, na qual se avaliou os eventos adversos ao trastuzumabe em monoterapia e/ou combinado com a quimioterapia descritos nos prontuários e por meio de exames laboratoriais e dos resultados do ecocardiograma. Foram utilizados modelos de regressão logística para estimar odds ratios e seus respectivos intervalos de confiança de 95%, com a finalidade de verificar a associação dos eventos adversos mais frequentes e uma série de variáveis sociodemográficas e clínicas das mulheres. Parte B: prospectiva, na qual, além da avaliação dos eventos adversos, foi também avaliada a QV das pacientes por meio do questionário específico para câncer QLQ-C30 e seu módulo de câncer de mama BR-23 da European Organization for Research and Treatment of Cancer (EORTC) em quatro momentos: antes do início da quimioterapia, após o término da quimioterapia, durante o uso do trastuzumabe e após o término do uso trastuzumabe. Análise de variância (ANOVA) para medidas repetidas foi utilizada para as comparações entre os escores médios obtidos das escalas e itens individuais dos questionários. Resultados Parte A: Foram analisados os prontuários de 79 pacientes que iniciaram o trastuzumabe entre 2007 e 2011. A incidência de reações imunes relacionadas a infusão do trastuzumabe aconteceu em 16 (20,3%) pacientes. A cardiotoxicidade ocorreu em 26 (32,9%) pacientes, sendo que treze (16,4%) destas interromperam permanentemente o tratamento, três (3,8%) interromperam temporariamente e 10 xi (12,6%) terminaram o tratamento sem interrupção. Com relação aos outros eventos adversos, os mais frequentes apresentados com o uso da quimioterapia combinada com o trastuzumabe foram dor (20,4%), náusea e vômito (15,9%), febre (9,7%), e neutropenia (7,1%), sendo apresentados por 55,7% das mulheres. Com relação ao uso do trastuzumabe em monoterapia, os mais frequentes foram: dor (19,6%), fadiga (10,8%), náusea e vômito (9,8%), e cefaleia (8,8%) apresentados por 49,4% das mulheres. Com exceção da cardiotoxicidade, nenhum outro evento adverso levou à descontinuação do tratamento. Não foram encontradas associações entre os eventos adversos mais frequentes e as variáveis sociodemográficas e clínicas das pacientes pelos modelos de regressão logística. Resultados Parte B: Dez pacientes foram incluídas no estudo, no período de outubro de 2011 a julho de 2012. Durante o uso do trastuzumabe e após o seu término foi observada uma melhora significativa da QV das pacientes nos parâmetros fadiga e efeitos colaterais sistêmicos, em comparação com o momento em que estavam utilizando os quimioterápicos. Entretanto estudos mais extensos com uma maior população são necessários para que possa ser avaliada a existência de associação entre os dados clínicos e sociodemográficos das pacientes como os resultados de QV. Conclusão: Embora o trastuzumabe seja um medicamento relativamente seguro para o tratamento do câncer de mama HER2 positivo, este pode causas alguns eventos adversos. Na população estudada, o único evento que levou à interrupção do tratamento foi a cardiotoxicidade, entretanto outros estudos mostraram que outros eventos adversos também foram capazes de ocasionar a descontinuação do tratamento. Para tanto são necessários que sejam tomados alguns cuidados para a prevenção e manejo desses eventos adversos, como um acompanhamento mais regular da função cardíaca e monitoramento constante das pacientes durante a infusão do trastuzumabe. Além disso, o trastuzumabe mostrou ter efeito positivo sobre a QV das pacientes. A avaliação da QV é importante, pois fornece informações clínica úteis em relação ao real impacto do tratamento proposto sobre a saúde e bem-estar das pacientes e pode também orientar na busca de estratégicas para minimizar os eventos adversos ao tratamento. / Introduction: Breast cancer is the second most common cancer in the world, with about 1.67 million new cases and 521,000 deaths each year. Breast cancer can be classified into different groups, being the HER2 positive subtype one of the most aggressive and related to a poor prognosis. However, new therapies that target the HER2 receptor have been developed in order to improve the conditions of patients. Among them is trastuzumab, a recombinant humanized monoclonal antibody of the IgG1 type, which binds with high affinity to the extracellular domain of the HER2 receptor. The use of trastuzumab is associated with an increase in the survival rate of women with HER2 positive breast cancer. Trastuzumab is generally well tolerated, but may have some adverse events, among them the cardiotoxicity, which can lead to treatment discontinuation, depriving patients of the benefits of this therapy. In addition to this effect, others may affect patient satisfaction such as immune reactions related to the infusion of trastuzumab, gastrointestinal events, fatigue, among others. In order to improve health care, it is necessary to assess treatment adverse events and quality of life (QoL) of women with HER2-positive breast cancer that uses trastuzumab to contribute to the increase in their welfare and ensure better treatment results. Objective: To evaluate the pharmacoepidemiological profile of women with HER2-positive breast cancer that used trastuzumab attended by Brazilian public health system, in the General Hospital of Ribeirão Preto Medical School, University of São Paulo. Patients and methods: This is an observational, descriptive and quantitative study, which was conducted in two parts. Part A: retrospective, in which it was evaluated the adverse events to trastuzumab alone and / or combined with chemotherapy described in the medical records and by laboratory tests and echocardiogram results. We used logistic regression models to estimate odds ratios and their 95% confidence intervals to verify the association of the most frequent adverse events and a number of sociodemographic and clinical variables. Part B: prospective, in which besides the evaluation of adverse events it was also evaluated the QoL of patients through the specific questionnaire QLQ-C30 cancer and its breast cancer module BR-23 from the European Organization for Research and Treatment of Cancer (EORTC) in four moments: before the start of chemotherapy, after the end of chemotherapy, during the use of trastuzumab and after the trastuzumab use. Results Part A: The medical records of 79 patients who started the trastuzumab between 2007 and 2011 were analysed. The incidence of immune reactions related to the infusion of trastuzumab occurred in 16 (20.3%) patients. Cardiotoxicity occurred in 26 (32.9%) patients, and 13 (16.4%) of these permanently discontinued the treatment, three (3.8%) discontinued temporarily and 10 (12.6%) completed treatment without interruption. In relation to the other adverse events, the most common events described with the use of trastuzumab combined with chemotherapy were pain (20.4%), nausea and vomiting (15.9%), fever (9.7%), and neutropenia (7.1%), being presented by 55.7% of women. Regarding the use of trastuzumab in monotherapy, the most common were pain (19.6%), fatigue (10.8%), nausea and vomiting (9.8%) and headache (8.8%) presented by 49.4% of women. Except for cardiotoxicity, no other adverse events led to treatment discontinuation. xiii No associations were found between the most frequent adverse events and the sociodemographic and clinical variables of the patients by logistic regression models. Results Part B: Ten patients were included in the study from October 2011 to July 2012. During the use of trastuzumab and after its completion, a significant improvement in QoL of patients on the parameters fatigue and systemic side effects were observed in comparison with the moment they were using chemotherapy. Nevertheless, larger studies with a larger population are needed in order to evaluate if there is an association between clinical and social demographic data of the patients with the results of QoL. Conclusion: Although trastuzumab is a relatively safe medication for the treatment of HER2 positive breast cancer, it may cause some adverse events. In this population, the only event that led to treatment interruption was cardiotoxicity, although other studies have shown that other adverse events were also able to cause treatment discontinuation. Therefore, some precaution needs to be taken for the prevention and management of those adverse events, such as a more regular monitoring of cardiac function and constant monitoring of patients during trastuzumab infusion. Furthermore, trastuzumab has shown to have a positive effect on patients QoL. The assessment of QoL is important as it provides useful clinical information regarding the real impact of the proposed treatment on the health and welfare of patients and can also guide the search for strategies to minimize treatment adverse events.
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Unravelling Drug Resistance Mechanisms in Breast Cancervon der Heyde, Silvia 04 June 2015 (has links)
No description available.
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Rôle de la tarification de l'activité des établissements de santé dans l'accès des patients aux traitements anticancéreux oraux : exemple du cancer du sein métastatique HER2+ / Role of the tariff of activity health facilities in patient access the oral cancer treatment : example of breast cancer metastatic HER2 +Benjamin, Laure 30 November 2012 (has links)
Depuis le début des années 2000, les traitements anticancéreux oraux (TAO) sont en développement croissant, notamment dans le cancer du sein. Ils permettent aux patients la prise de comprimés par voie orale à domicile améliorant la qualité de vie. On estime que 10 à 34% des tumeurs du sein sur-expriment la protéine HER2 (HER2+) qui augmente le risque de métastases. Deux thérapies ciblées anti-HER2 sont actuellement disponibles : le trastuzumab, anticorps monoclonal administré par voie intraveineuse et le lapatinib, inhibiteur de tyrosine kinase administré par voie orale. D’après les recommandations de l’Agence Nationale d’Accréditation et d’Evaluation en Santé (ANAES, 2003), les TAO devraient être privilégiées par rapport aux formes intraveineuses prises à l’hôpital lorsque leur efficacité est équivalente. Dans la pratique courante des oncologues, les TAO semblent néanmoins sous-utilisées dans certains cas. En plus des freins médicaux connus (adhésion thérapeutique, gestion des effets indésirables), les TAO induisent une consommation de ressources hopitalières supplémentaires qui n’est pas valorisée dans le modèle de tarification à l’activité (T2A) des établissements hospitaliers, lequel repose sur la nature et la quantité d’activité médicale réalisée. Nous supposons que le modèle de T2A représente un frein économique à l’utilisation des TAO entrainant une disparité d’accès entre les traitements anticancéreux oraux et intraveineux. L’objectif de ce travail de thèse était donc de déterminer le rôle de la T2A dans l’accès des patients aux TAO au moyen d’une évaluation médico- économique de l’impact économique et organisationnel des TAO sur le système de soins. Une revue de littérature a permis de mettre en évidence le rôle du mode de financement des soins sur l’accès aux TAO en France et aux Etats-Unis. L’analyse des bases de données nationales hospitalières du Programme Médicalisé des Systèmes d’Information (PMSI) a permis de quantifier l’enjeu économique de la chimiothérapie pour les établissements de soins et qui représente la deuxième activité des hôpitaux en volume après l’hémodialyse. Le bénéfice lié aux séances de chimiothérapie a ainsi été estimé à 108 millions d’Euros en 2010 pour l’ensemble des établissements publics et privés en France. L’analyse a également permis de simuler le transfert d’allocation de ressources de l’hôpital vers les soins de ville induit par la substitution des séances de chimiothérapie par l’utilisation des TAO. Un modèle comparant le coût du traitement intraveineux (trastuzumab) aux TAO (lapatinib et capécitabine) dans le cancer du sein métastatique HER2+ a confirmé des coûts moindres pour les TAO (17 165€ versus 36 077€ par an et par patient) liés à une économie sur les transports médicalisés mais surtout sur les consommations hospitalières et ce, malgré un coût d’acquisition plus élevé des TAO. Malgré cet impact budgétaire négatif pour les hôpitaux, une étude de préférences (Méthode des Choix Discrets) conduite auprès d’un échantillon de 203 médecins hospitaliers et libéraux a montré que l’efficacité d’un traitement anticancéreux restait le déterminant principal de la décision thérapeutique (β=2,214, p<0,0001). L’étude a toutefois révélé que, aux stades avancés du cancer, la voie d’administration et son coût étaient également associés au choix du traitement (β=0,612, p=0,035 ;β=0,506, p<0,0001). Les résultats montrent donc que le modèle de financement de l’activité hospitalière influence le choix des modalités de traitement même si les critères d’ordre médicaux et environnementaux du patient demeurent des déterminants essentiels dans le choix du recours aux TAO (profil clinique du patient, adhésion thérapeutique, préférences du patient, environnement familial et socio-économique, conditions d’accès à l’offre de soins) / Since the early 2000’s, oral anticancer drugs (OADs) are increasingly available especially for the treatment of breast cancer. This route of chemotherapy administration allows patients to take oral tablets at home improving their quality-of-life. We estimate that 10 to 34% of breast tumors over-express the HER2 protein (HER2+) that increases the risk of developing metastasis. Two anti-HER2 targeted therapies are currently available: trastuzumab, a monoclonal antibody administered intravenously and lapatinib, a tyrosine kinase inhibitor administered orally. According to the recommendations of the National Agency for Accreditation and Evaluation in Health (ANAES, 2003), OADs should be administered when their efficacy is equivalent to the one of intravenous forms taken at hospital. In the current practice of oncologists, OADs seem to be underused in some cases. The medical brakes to the use of OADs (i.e. adherence, management of side effects) are well known. Nonetheless, OADs induce additional hospital healthcare resources which are not taken into account in the hospital payment system that is based on the nature and the quantity of medical activities performed (i.e. per-case payment system (PPS)). We assume that the current model of PPS represents an economic barrier to the use of OADs and which induces a disparity of access between oral and intravenous cancer treatments. The objective of this thesis was to determine the role of the PPS on the patient access to OADs based on a medico-economic evaluation of the economical and organizational impacts of OADs on the health care system. A literature review has highlighted the role of the funding of care on the access to OADs in the French and US healthcare systems. From an analysis of the national hospital database (PMSI database), we have quantified the economic implications of chemotherapy administration that is the second hospital activity in volume after hemodialysis. Earnings associated with chemotherapy sessions have been estimated at 108 million Euros in 2010 for all private and public institutions in France. This analysis also allowed us to simulate the transfer of resources allocation from hospital to community setting induced by the substitution of chemotherapy sessions by the use of OADs. A model comparing the cost of intravenous anticancer drug (trastuzumab) to OADs (lapatinib and capecitabine) in the treatment of HER2+ metastatic breast cancer confirmed the lower costs for OADs (€ 17,165 versus € 36,077 per year per patient). The higher acquisition cost of OADs was offset by the cost savings in terms of medical transportation and hospital resources. Despite this negative budget impact for hospitals, a preference study (Discrete Choice Experiment) conducted among 203 physicians showed that the efficacy of cancer treatment remained the main determinant of the therapeutic decision (β=2.214, p<0.0001). The study has also revealed that, in the advanced stages of cancer, the route of administration and its associated cost was also associated with the treatment choice (β=0.612, p= 0.035; =β0.506, p<0.0001). Overall, the results show that the hospital payment system influences the choice of treatment modalities. Nonetheless, medical criterions related to the patient remain essential in the choice of using OADs (clinical profile of the patient, adherence, patient preferences, familial and socio-economic environment, and conditions of access to health care)
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