title: Modeling of response to endocrine therapy in a panel of human luminal breast cancer xenografts.
abstract: 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.
authors: Department of Medical Oncology, Institut Curie, Paris, France. paul.cottu@curie.net
authors: P
authors: P
authors: Cottu
authors: E
authors: E
authors: Marangoni
authors: F
authors: F
authors: Assayag
authors: P
authors: P
authors: de Cremoux
authors: A
authors: A
authors: Vincent-Salomon
authors: Ch
authors: Ch
authors: Guyader
authors: L
authors: L
authors: de Plater
authors: C
authors: C
authors: Elbaz
authors: N
authors: N
authors: Karboul
authors: J J
authors: JJ
authors: Fontaine
authors: S
authors: S
authors: Chateau-Joubert
authors: P
authors: P
authors: Boudou-Rouquette
authors: S
authors: S
authors: Alran
authors: V
authors: V
authors: Dangles-Marie
authors: D
authors: D
authors: Gentien
authors: M-F
authors: MF
authors: Poupon
authors: D
authors: D
authors: Decaudin
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology*; D055028:Comparative Genomic Hybridization; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D016896:Treatment Outcome; D047368:Tumor Burden; D023041:Xenograft Model Antitumor Assays
chemical_list: D018931:Antineoplastic Agents, Hormonal; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone