Establishing and characterizing patient-derived xenografts using pre-chemotherapy percutaneous biopsy and post-chemotherapy surgical samples from a prospective neoadjuvant breast cancer study

Jia Yu, Bo Qin, Ann Moyer, Jason P. Sinnwell, Kevin J. Thompson, John A III Copland, Laura A. Marlow, James L. Miller, Ping Yin, Bowen Gao, Katherine Minter-Dykhouse, Xiaojia Tang, Sarah A. McLaughlin, Alvaro Moreno Aspitia, Anthony Schweitzer, Yan Lu, Jason Hubbard, Donald W Northfelt, Richard J. Gray, Katie HuntAmy L. Conners, Vera Jean Suman, Krishna R Kalari, James N. Ingle, Zhenkun Lou, Daniel W Visscher, Richard M Weinshilboum, Judy C Boughey, Matthew Philip Goetz, Liewei M Wang

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Number of pages1
JournalBreast cancer research : BCR
Volume19
Issue number1
DOIs
StatePublished - Dec 6 2017

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Heterografts
Breast Neoplasms
Biopsy
Drug Therapy
Neoplasms
Residual Neoplasm
Pharmaceutical Preparations
Triple Negative Breast Neoplasms
Anthracyclines
Drug Discovery
Paclitaxel
Biomarkers

Keywords

  • Breast cancer
  • Patient-derived Xenograft (PDX)
  • Percutaneous tumor biopsies (PTB)
  • Pre-clinical therapy
  • Prospective neoadjuvant chemotherapy (NAC)

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Establishing and characterizing patient-derived xenografts using pre-chemotherapy percutaneous biopsy and post-chemotherapy surgical samples from a prospective neoadjuvant breast cancer study. / Yu, Jia; Qin, Bo; Moyer, Ann; Sinnwell, Jason P.; Thompson, Kevin J.; Copland, John A III; Marlow, Laura A.; Miller, James L.; Yin, Ping; Gao, Bowen; Minter-Dykhouse, Katherine; Tang, Xiaojia; McLaughlin, Sarah A.; Moreno Aspitia, Alvaro; Schweitzer, Anthony; Lu, Yan; Hubbard, Jason; Northfelt, Donald W; Gray, Richard J.; Hunt, Katie; Conners, Amy L.; Suman, Vera Jean; Kalari, Krishna R; Ingle, James N.; Lou, Zhenkun; Visscher, Daniel W; Weinshilboum, Richard M; Boughey, Judy C; Goetz, Matthew Philip; Wang, Liewei M.

In: Breast cancer research : BCR, Vol. 19, No. 1, 06.12.2017.

Research output: Contribution to journalArticle

Yu, Jia ; Qin, Bo ; Moyer, Ann ; Sinnwell, Jason P. ; Thompson, Kevin J. ; Copland, John A III ; Marlow, Laura A. ; Miller, James L. ; Yin, Ping ; Gao, Bowen ; Minter-Dykhouse, Katherine ; Tang, Xiaojia ; McLaughlin, Sarah A. ; Moreno Aspitia, Alvaro ; Schweitzer, Anthony ; Lu, Yan ; Hubbard, Jason ; Northfelt, Donald W ; Gray, Richard J. ; Hunt, Katie ; Conners, Amy L. ; Suman, Vera Jean ; Kalari, Krishna R ; Ingle, James N. ; Lou, Zhenkun ; Visscher, Daniel W ; Weinshilboum, Richard M ; Boughey, Judy C ; Goetz, Matthew Philip ; Wang, Liewei M. / Establishing and characterizing patient-derived xenografts using pre-chemotherapy percutaneous biopsy and post-chemotherapy surgical samples from a prospective neoadjuvant breast cancer study. In: Breast cancer research : BCR. 2017 ; Vol. 19, No. 1.
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abstract = "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.",
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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

AU - Sinnwell, Jason P.

AU - Thompson, Kevin J.

AU - Copland, John A III

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 Jean

AU - Kalari, Krishna R

AU - Ingle, James N.

AU - Lou, Zhenkun

AU - Visscher, Daniel W

AU - Weinshilboum, Richard M

AU - Boughey, Judy C

AU - Goetz, Matthew Philip

AU - Wang, Liewei M

PY - 2017/12/6

Y1 - 2017/12/6

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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DO - 10.1186/s13058-017-0920-8

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