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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’s 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,

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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 < 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’s 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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            name:Institut Curie
            address:
               name:Department of Surgical Oncology, Institut Curie, Paris, France
               type:PostalAddress
            type:Organization
      name:V. Dangles-Marie
      affiliation:
            name:Hôpital St Louis
            address:
               name:Laboratory of Preclinical Investigations, Institut Curie Translational Research Department, Hôpital St Louis, Paris, France
               type:PostalAddress
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      name:D. Gentien
      affiliation:
            name:Hôpital St Louis
            address:
               name:Molecular Biology Facilities, Institut Curie Translational Research Department, Hôpital St Louis, Paris, France
               type:PostalAddress
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      name:M.-F. Poupon
      affiliation:
            name:Hôpital St Louis
            address:
               name:Laboratory of Preclinical Investigations, Institut Curie Translational Research Department, Hôpital St Louis, Paris, France
               type:PostalAddress
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      name:D. Decaudin
      affiliation:
            name:Institut Curie
            address:
               name:Department of Medical Oncology, Institut Curie, Paris, France
               type:PostalAddress
            type:Organization
            name:Hôpital St Louis
            address:
               name:Laboratory of Preclinical Investigations, Institut Curie Translational Research Department, Hôpital St Louis, Paris, France
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      email:[email protected]
PostalAddress:
      name:Department of Medical Oncology, Institut Curie, Paris, France
      name:Laboratory of Preclinical Investigations, Institut Curie Translational Research Department, Hôpital St Louis, Paris, France
      name:Laboratory of Preclinical Investigations, Institut Curie Translational Research Department, Hôpital St Louis, Paris, France
      name:Laboratory of Preclinical Investigations, Institut Curie Translational Research Department, Hôpital 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, Hôpital St Louis, Paris, France
      name:Laboratory of Preclinical Investigations, Institut Curie Translational Research Department, Hôpital St Louis, Paris, France
      name:Laboratory of Preclinical Investigations, Institut Curie Translational Research Department, Hôpital St Louis, Paris, France
      name:Laboratory of Preclinical Investigations, Institut Curie Translational Research Department, Hôpital St Louis, Paris, France
      name:Pathology Department, Ecole Nationale Vétérinaire d’Alfort, Maisons Alfort, France
      name:Pathology Department, Ecole Nationale Vétérinaire d’Alfort, 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, Hôpital St Louis, Paris, France
      name:Molecular Biology Facilities, Institut Curie Translational Research Department, Hôpital St Louis, Paris, France
      name:Laboratory of Preclinical Investigations, Institut Curie Translational Research Department, Hôpital St Louis, Paris, France
      name:Department of Medical Oncology, Institut Curie, Paris, France
      name:Laboratory of Preclinical Investigations, Institut Curie Translational Research Department, Hôpital St Louis, Paris, France
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