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

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

  • Breast Cancer Res. 2017 Dec 6;19(1):130. doi: 10.1186/s13058-017-0920-8.
Jia Yu 1,  Bo Qin 1 2,  Ann M Moyer 3,  Jason P Sinnwell 4,  Kevin J Thompson 4,  John A Copland 3rd 5,  Laura A Marlow 5,  James L Miller 5,  Ping Yin 2,  Bowen Gao 6,  Katherine Minter-Dykhouse 2,  Xiaojia Tang 4,  Sarah A McLaughlin 7,  Alvaro Moreno-Aspitia 8,  Anthony Schweitzer 9,  Yan Lu 9,  Jason Hubbard 9,  Donald W Northfelt 10,  Richard J Gray 11,  Katie Hunt 12,  Amy L Conners 12,  Vera J Suman 4,  Krishna R Kalari 4,  James N Ingle 2,  Zhenkun Lou 2,  Daniel W Visscher 3,  Richard Weinshilboum 1,  Judy C Boughey 13,  Matthew P Goetz 1 2,  Liewei Wang 14
Affiliations

Affiliations

  • 1 Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA.
  • 2 Department of Oncology, Mayo Clinic, Rochester, MN, 55905, USA.
  • 3 Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, 55905, USA.
  • 4 Department of Health Sciences Research, Mayo Clinic, Rochester, MN, 55905, USA.
  • 5 Department of Cancer Biology, Mayo Clinic, Jacksonville, FL, 32224, USA.
  • 6 Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.
  • 7 Department of Surgery, Mayo Clinic, Jacksonville, FL, 32224, USA.
  • 8 Department of Hematology/Oncology, Mayo Clinic, Jacksonville, FL, 32224, USA.
  • 9 Affymetrix, now part of Thermo Fisher Scientific, Santa Clara, CA, 95051, USA.
  • 10 Department of Hematology/Oncology, Mayo Clinic, Scottsdale, AZ, 85259, USA.
  • 11 Department of Surgery, Mayo Clinic, Scottsdale, AZ, 85259, USA.
  • 12 Department of Radiology, Mayo Clinic, Rochester, MN, 55905, USA.
  • 13 Department of Surgery, Mayo Clinic, Rochester, MN, 55905, USA.
  • 14 Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA. Wang.Liewei@mayo.edu.
PMID: 29212525 DOI: 10.1186/s13058-017-0920-8
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.

Keywords

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

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