The inter- and intra-tumor heterogeneity of breast cancer needs to be adequately captured in pre-clinical models. We have created a large collection of breast cancer patient-derived tumor xenografts (PDTXs), in which the morphological and molecular characteristics of the originating tumor are preserved through passaging in the mouse. An integrated platform combining in vivo maintenance of these PDTXs along with short-term cultures of PDTX-derived tumor cells (PDTCs) was optimized. Remarkably, the intra-tumor genomic clonal architecture present in the originating breast cancers was mostly preserved upon serial passaging in xenografts and in short-term cultured PDTCs. We assessed drug responses in PDTCs on a high-throughput platform and validated several ex vivo responses in vivo. The biobank represents a powerful resource for pre-clinical breast cancer pharmacogenomic studies (http://caldaslab.cruk.cam.ac.uk/bcape), including identification of biomarkers of response or resistance.This research was supported with funding from Cancer Research UK and from
the European Union to the EUROCAN Network of Excellence (FP7; grant numnumber
260791). M.C. has received funding from the European Union’s Horizon
2020 research and innovation program under the Marie Sk1odowska-Curie
grant agreement no. 660060 and was supported by the Department of Experimental
Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale
dei Tumori, Milan, Italy. R.N.B. is supported by the Wellcome Trust PhD
Programme in Mathematical Genomics and Medicine. S-J.S. is supported
by the Wellcome Trust PhD Programme for Clinicians in Cambridge. A.Bruna,
O.M.R., E.M., V.S., and C.C. are members of the EurOPDX Consortium. Weare
very grateful for the generosity of all the patients that donated samples for implantation.
We are also deeply indebted to all the staff (surgeons, pathologists,
oncologists, theatre staff, and other ancillary personnel) at the Cambridge
Breast Unit, Cambridge University Hospital NHS Foundation Trust, for facilitating
the timely collection of samples. We thank the Cancer Research UK
Cambridge Institute Genomics, Bioinformatics, Histopathology, Flow Cytometry,
Biological Resource, and Bio-repository Core Facilities for support during
the execution of this project.This is the final version of the article. It first appeared from Elsevier at http://dx.doi.org/10.1016/j.cell.2016.08.041