Human breast-cancer xenografts in immune-suppressed mice

Bailey, M J; Gazet, J.‐C.; Peckham, M. J.

doi:10.1038/bjc.1980.275

Cited by 32 publications

(12 citation statements)

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“…ER-positive HBC have slow-growing properties (13), a low grade, or slow proliferation (14). Our failure to establish more ER-positive HBCx is in accordance with data reported by the Fribourg group (1) and other authors (15), who showed that ER-negative tumors were easier to establish in mice. The weak tumor take could also be attributed to differences between the hormonal status of female mice and women.…”

Section: Discussionsupporting

confidence: 91%

A New Model of Patient Tumor-Derived Breast Cancer Xenografts for Preclinical Assays

Marangoni¹,

Vincent‐Salomon²,

Auger³

et al. 2007

Clinical Cancer Research

371

374

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Purpose:To establish a panel of human breast cancer (HBC) xenografts in immunodeficient mice suitable for pharmacologic preclinical assays. Experimental Design: 200 samples of HBCs were grafted into Swiss nude mice. Twenty-five transplantable xenografts were established (12.5%). Their characterization included histology, p53 status, genetic analysis by array comparative genomic hybridization, gene expression by Western blotting, and quantitative reverse transcription-PCR. Biological profiles of nine xenografts were compared with those of the corresponding patient's tumor. Chemosensitivities of 17 xenografts to a combination of Adriamycin and cyclophosphamide (AC), docetaxel, trastuzumab, and Degarelix were evaluated. Results: Almost all patient tumors established as xenografts displayed an aggressive phenotype, i.e., high-grade, triple-negative status. The histology of the xenografts recapitulated the features of the original tumors. Mutation of p53 and inactivation of Rb and PTEN proteins were found in 83%, 30%, and 42% of HBC xenografts, respectively. Two HBCx had an ERBB2 (HER2) amplification. Large variations were observed in the expression of HER family receptors and in genomic profiles. Genomic alterations were close to those of original samples in paired tumors. Three xenografts formed lung metastases. A total of 15 of the 17 HBCx (88%) responded to AC, and 8 (47%) responded to docetaxel. One ERBB2-amplified xenograft responded to trastuzumab, whereas the other did not. The drug response of HBC xenografts was concordant with that of the patient's tumor in five of seven analyzable cases. Breast cancer is one of the most frequently diagnosed types of cancer in women and a leading cause of cancer-related death in women. The incidence of breast cancer has increased by twothirds over the last 15 years. However, mortality has decreased by one-third due to the earlier detection of breast cancer and increasing use of systemic therapies. Recently, new chemotherapy agents and molecular targeted therapies, such as trastuzumab, have provided a real hope of decreasing breast cancer mortality. However, despite appropriate adjuvant systemic therapy, up to 30% of patients will relapse. The vast majority of deaths are caused by recurrent metastatic disease. To date, patients relapsing will frequently have received multiple therapies in the adjuvant setting (anthracycline-taxane -based chemotherapy, hormonotherapy, and trastuzumab in case of ERBB2 amplification). Therefore, it is clear that novel compounds are required in the metastatic setting. Considering the numerous compounds produced by pharmaceutical companies, we need new tools to speed up clinical development and to take into account the heterogeneity of the disease. Preclinical models are one potential solution. A preclinical screening step in drug development must predict not only the antitumoral activity of new compounds, but also in which tumor type or subtype the compound will be effective. The preclinical models presently used are not predictive enou...

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Section: Discussionsupporting

confidence: 91%

A New Model of Patient Tumor-Derived Breast Cancer Xenografts for Preclinical Assays

Marangoni¹,

Vincent‐Salomon²,

Auger³

et al. 2007

Clinical Cancer Research

371

374

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“…Further attempts to improve the receptivity of mice to xenografts were reported by Bailey et al, (1980a). In an effort to improve the take-rate of human breast tumours, which have widely been found difficult to graft, a variety of modifications were made to the immuno-suppression procedure.…”

mentioning

confidence: 99%

The response to chemotherapy of a variety of human tumour xenografts

Steel¹,

Courtenay²,

Peckham³

1983

Br J Cancer

Self Cite

161

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“…There was no evidence that any of these manoeuvres increased the take rate. Details of these and other manipulations have been published elsewhere (Bailey et al, 1980a).…”

Section: Resultsmentioning

confidence: 99%