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Title:
Modeling of response to endocrine therapy in a panel of human luminal breast cancer xenografts | Breast Cancer Research and Treatment
Description:
Resistance to endocrine therapy is a major complication of luminal breast cancer and studies of the biological features of hormonal resistance are limited by the lack of adequate preclinical models. The aim of this study is to establish and characterize a panel of primary human luminal breast carcinoma xenografts, and to evaluate their response to endocrine therapies. Four hundred and twenty-three tumor fragments obtained directly from patients have been grafted in the interscapular fatpad of Swiss nude mice. After stable engraftment with estradiol supplementation, xenografted tumors have been validated by conventional pathology and immunohistochemistry examination, and additional molecular studies. In vivo tumor growth and response to different endocrine treatments were evaluated. We have engrafted 423 tumors including 314 ER+ tumors, and 8 new luminal breast cancer xenografts have been obtained (2.5%). Tumor take was much lower for luminal tumors than for non-luminal tumors (2.5 vs. 24.7%, P < 0.0001), and was associated with two independent criteria, i.e., ER status (P < 0.0001) and a high grade tumor (P = 0.05). Histological and immunohistochemical analyses performed on patient鈥檚 tumors and xenografts showed striking similarities in the tumor morphology as well as in the expression level of ER, PR, and HER2. Response to hormone therapy, evaluated in 6 luminal models, showed different sensitivities, thus exhibiting heterogeneity similar to what is observed in the clinic. We have established a panel of primary human luminal breast cancer xenografts, recapitulating the biological and clinical behaviors of patient tumors, and therefore suitable for further preclinical experiments.
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cancer, breast, article, google, scholar, pubmed, cas, endocrine, xenografts, luminal, tumor, therapy, human, research, response, mice, tumors, characterization, institut, curie, cottu, hormone, access, clin, oncol, department, supplementary, treatment, study, vincentsalomon, models, patients, growth, tamoxifen, france, privacy, cookies, content, preclinical, marangoni, assayag, cremoux, decaudin, immunohistochemistry, therapeutic, paris, hbcx, data, publish, search,
Topics {鉁掞笍}
22th eortc-nci-aacr conference month download article/chapter early-stage breast cancer mammary epithelial-specific ablation luminal breast cancer patient-level meta-analysis human breast carcinomas translational research department modelling breast cancer invasive breast cancer endocrine therapy testing breast cancer metastasis related subjects estrogen receptor variants full article pdf breast cancer patients endocrine therapies privacy choices/manage cookies adequate preclinical models vivo tumor growth breast cancer patient tumor sampling ave claude vellefaux check access instant access luminal xenografts 6 luminal models human cells tumor biology teams breast carcinoma european economic area scope submit manuscript germline brca2 mutation hormonal receptors fluorescent inhibition screening h么pital st louis ecole nationale v茅t茅rinaire extended therapeutic characterization metastatic properties institut curie foundation electronic supplementary material conditions privacy policy cancer cell 10 hormonal resistance van de vijver de matos granja high grade tumor endocrine treatments hormone therapy exhibiting heterogeneity similar
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headline:Modeling of response to endocrine therapy in a panel of human luminal breast cancer xenografts
description:Resistance to endocrine therapy is a major complication of luminal breast cancer and studies of the biological features of hormonal resistance are limited by the lack of adequate preclinical models. The aim of this study is to establish and characterize a panel of primary human luminal breast carcinoma xenografts, and to evaluate their response to endocrine therapies. Four hundred and twenty-three tumor fragments obtained directly from patients have been grafted in the interscapular fatpad of Swiss nude mice. After stable engraftment with estradiol supplementation, xenografted tumors have been validated by conventional pathology and immunohistochemistry examination, and additional molecular studies. In vivo tumor growth and response to different endocrine treatments were evaluated. We have engrafted 423 tumors including 314 ER+ tumors, and 8 new luminal breast cancer xenografts have been obtained (2.5%). Tumor take was much lower for luminal tumors than for non-luminal tumors (2.5 vs. 24.7%, P聽<聽0.0001), and was associated with two independent criteria, i.e., ER status (P聽<聽0.0001) and a high grade tumor (P聽=聽0.05). Histological and immunohistochemical analyses performed on patient鈥檚 tumors and xenografts showed striking similarities in the tumor morphology as well as in the expression level of ER, PR, and HER2. Response to hormone therapy, evaluated in 6 luminal models, showed different sensitivities, thus exhibiting heterogeneity similar to what is observed in the clinic. We have established a panel of primary human luminal breast cancer xenografts, recapitulating the biological and clinical behaviors of patient tumors, and therefore suitable for further preclinical experiments.
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Endocrine therapy modeling
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description:Resistance to endocrine therapy is a major complication of luminal breast cancer and studies of the biological features of hormonal resistance are limited by the lack of adequate preclinical models. The aim of this study is to establish and characterize a panel of primary human luminal breast carcinoma xenografts, and to evaluate their response to endocrine therapies. Four hundred and twenty-three tumor fragments obtained directly from patients have been grafted in the interscapular fatpad of Swiss nude mice. After stable engraftment with estradiol supplementation, xenografted tumors have been validated by conventional pathology and immunohistochemistry examination, and additional molecular studies. In vivo tumor growth and response to different endocrine treatments were evaluated. We have engrafted 423 tumors including 314 ER+ tumors, and 8 new luminal breast cancer xenografts have been obtained (2.5%). Tumor take was much lower for luminal tumors than for non-luminal tumors (2.5 vs. 24.7%, P聽<聽0.0001), and was associated with two independent criteria, i.e., ER status (P聽<聽0.0001) and a high grade tumor (P聽=聽0.05). Histological and immunohistochemical analyses performed on patient鈥檚 tumors and xenografts showed striking similarities in the tumor morphology as well as in the expression level of ER, PR, and HER2. Response to hormone therapy, evaluated in 6 luminal models, showed different sensitivities, thus exhibiting heterogeneity similar to what is observed in the clinic. We have established a panel of primary human luminal breast cancer xenografts, recapitulating the biological and clinical behaviors of patient tumors, and therefore suitable for further preclinical experiments.
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email:[email protected]
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name:Department of Medical Oncology, Institut Curie, Paris, France
name:Laboratory of Preclinical Investigations, Institut Curie Translational Research Department, H么pital St Louis, Paris, France
name:Laboratory of Preclinical Investigations, Institut Curie Translational Research Department, H么pital St Louis, Paris, France
name:Laboratory of Preclinical Investigations, Institut Curie Translational Research Department, H么pital St Louis, Paris, France
name:Department of Pathology and Tumor Biology, Institut Curie, Paris, France
name:Department of Pathology and Tumor Biology, Institut Curie, Paris, France
name:Laboratory of Preclinical Investigations, Institut Curie Translational Research Department, H么pital St Louis, Paris, France
name:Laboratory of Preclinical Investigations, Institut Curie Translational Research Department, H么pital St Louis, Paris, France
name:Laboratory of Preclinical Investigations, Institut Curie Translational Research Department, H么pital St Louis, Paris, France
name:Laboratory of Preclinical Investigations, Institut Curie Translational Research Department, H么pital St Louis, Paris, France
name:Pathology Department, Ecole Nationale V茅t茅rinaire d鈥橝lfort, Maisons Alfort, France
name:Pathology Department, Ecole Nationale V茅t茅rinaire d鈥橝lfort, Maisons Alfort, France
name:Department of Medical Oncology, Institut Curie, Paris, France
name:Department of Surgical Oncology, Institut Curie, Paris, France
name:Laboratory of Preclinical Investigations, Institut Curie Translational Research Department, H么pital St Louis, Paris, France
name:Molecular Biology Facilities, Institut Curie Translational Research Department, H么pital St Louis, Paris, France
name:Laboratory of Preclinical Investigations, Institut Curie Translational Research Department, H么pital St Louis, Paris, France
name:Department of Medical Oncology, Institut Curie, Paris, France
name:Laboratory of Preclinical Investigations, Institut Curie Translational Research Department, H么pital St Louis, Paris, France
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