TY - JOUR
T1 - Establishing and characterizing patient-derived xenografts using pre-chemotherapy percutaneous biopsy and post-chemotherapy surgical samples from a prospective neoadjuvant breast cancer study
AU - Yu, Jia
AU - Qin, Bo
AU - Moyer, Ann M.
AU - Sinnwell, Jason P.
AU - Thompson, Kevin J.
AU - Copland, John A.
AU - Marlow, Laura A.
AU - Miller, James L.
AU - Yin, Ping
AU - Gao, Bowen
AU - Minter-Dykhouse, Katherine
AU - Tang, Xiaojia
AU - McLaughlin, Sarah A.
AU - Moreno-Aspitia, Alvaro
AU - Schweitzer, Anthony
AU - Lu, Yan
AU - Hubbard, Jason
AU - Northfelt, Donald W.
AU - Gray, Richard J.
AU - Hunt, Katie
AU - Conners, Amy L.
AU - Suman, Vera J.
AU - Kalari, Krishna R.
AU - Ingle, James N.
AU - Lou, Zhenkun
AU - Visscher, Daniel W.
AU - Weinshilboum, Richard
AU - Boughey, Judy C.
AU - Goetz, Matthew P.
AU - Wang, Liewei
N1 - Publisher Copyright:
© 2017, The Author(s).
PY - 2017/12
Y1 - 2017/12
N2 - Background: Patient-derived xenografts (PDXs) are increasingly used in cancer research as a tool to inform cancer biology and drug response. Most available breast cancer PDXs have been generated in the metastatic setting. However, in the setting of operable breast cancer, PDX models both sensitive and resistant to chemotherapy are needed for drug development and prospective data are lacking regarding the clinical and molecular characteristics associated with PDX take rate in this setting. Methods: The Breast Cancer Genome Guided Therapy Study (BEAUTY) is a prospective neoadjuvant chemotherapy (NAC) trial of stage I-III breast cancer patients treated with neoadjuvant weekly taxane+/-trastuzumab followed by anthracycline-based chemotherapy. Using percutaneous tumor biopsies (PTB), we established and characterized PDXs from both primary (untreated) and residual (treated) tumors. Tumor take rate was defined as percent of patients with the development of at least one stably transplantable (passed at least for four generations) xenograft that was pathologically confirmed as breast cancer. Results: Baseline PTB samples from 113 women were implanted with an overall take rate of 27.4% (31/113). By clinical subtype, the take rate was 51.3% (20/39) in triple negative (TN) breast cancer, 26.5% (9/34) in HER2+, 5.0% (2/40) in luminal B and 0% (0/3) in luminal A. The take rate for those with pCR did not differ from those with residual disease in TN (p = 0.999) and HER2+ (p = 0.2401) tumors. The xenografts from 28 of these 31 patients were such that at least one of the xenografts generated had the same molecular subtype as the patient. Among the 35 patients with residual tumor after NAC adequate for implantation, the take rate was 17.1%. PDX response to paclitaxel mirrored the patients’ clinical response in all eight PDX tested. Conclusions: The generation of PDX models both sensitive and resistant to standard NAC is feasible and these models exhibit similar biological and drug response characteristics as the patients’ primary tumors. Taken together, these models may be useful for biomarker discovery and future drug development.
AB - Background: Patient-derived xenografts (PDXs) are increasingly used in cancer research as a tool to inform cancer biology and drug response. Most available breast cancer PDXs have been generated in the metastatic setting. However, in the setting of operable breast cancer, PDX models both sensitive and resistant to chemotherapy are needed for drug development and prospective data are lacking regarding the clinical and molecular characteristics associated with PDX take rate in this setting. Methods: The Breast Cancer Genome Guided Therapy Study (BEAUTY) is a prospective neoadjuvant chemotherapy (NAC) trial of stage I-III breast cancer patients treated with neoadjuvant weekly taxane+/-trastuzumab followed by anthracycline-based chemotherapy. Using percutaneous tumor biopsies (PTB), we established and characterized PDXs from both primary (untreated) and residual (treated) tumors. Tumor take rate was defined as percent of patients with the development of at least one stably transplantable (passed at least for four generations) xenograft that was pathologically confirmed as breast cancer. Results: Baseline PTB samples from 113 women were implanted with an overall take rate of 27.4% (31/113). By clinical subtype, the take rate was 51.3% (20/39) in triple negative (TN) breast cancer, 26.5% (9/34) in HER2+, 5.0% (2/40) in luminal B and 0% (0/3) in luminal A. The take rate for those with pCR did not differ from those with residual disease in TN (p = 0.999) and HER2+ (p = 0.2401) tumors. The xenografts from 28 of these 31 patients were such that at least one of the xenografts generated had the same molecular subtype as the patient. Among the 35 patients with residual tumor after NAC adequate for implantation, the take rate was 17.1%. PDX response to paclitaxel mirrored the patients’ clinical response in all eight PDX tested. Conclusions: The generation of PDX models both sensitive and resistant to standard NAC is feasible and these models exhibit similar biological and drug response characteristics as the patients’ primary tumors. Taken together, these models may be useful for biomarker discovery and future drug development.
KW - Breast cancer
KW - Patient-derived Xenograft (PDX)
KW - Percutaneous tumor biopsies (PTB)
KW - Pre-clinical therapy
KW - Prospective neoadjuvant chemotherapy (NAC)
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U2 - 10.1186/s13058-017-0920-8
DO - 10.1186/s13058-017-0920-8
M3 - Article
C2 - 29212525
AN - SCOPUS:85048269938
SN - 1465-5411
VL - 19
JO - Breast Cancer Research
JF - Breast Cancer Research
IS - 1
M1 - 130
ER -