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Different approaches have been used to develop three\u2010dimensional models able to recapitulate the complexity of the extracellular matrix. Here, we use cell\u2010free patient\u2010derived scaffolds (PDSs) generated from breast cancer samples that were recellularized with cancer cell lines as an in vivo\u2010like culture system for drug testing. We show that PDS cultured MCF7 cancer cells increased their resistance against the front\u2010line chemotherapy drugs 5\u2010fluorouracil, doxorubicin and paclitaxel in comparison to traditional two\u2010dimensional cell cultures. The gene expression of the environmentally adapted cancer cells was modulated in different ways depending on the drug and the concentration used. High doses of doxorubicin reduced cancer stem cell features, whereas 5\u2010fluorouracil increased stemness and decreased the proliferative phenotype. By using PDSs repopulated with other breast cancer cell lines, T\u201047D and MDA\u2010MB\u2010231, we observed both general and cell line specific drug responses. In summary, PDSs can be used to examine the extracellular matrix influence on cancer drug responses and for testing novel compounds in in vivo\u2010like microenvironments.<\/jats:p>","DOI":"10.1002\/jcp.30191","type":"journal-article","created":{"date-parts":[[2020,12,25]],"date-time":"2020-12-25T03:00:29Z","timestamp":1608865229000},"page":"4709-4724","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Breast cancer patient\u2010derived scaffolds as a tool to monitor chemotherapy responses in human tumor microenvironments"],"prefix":"10.1002","volume":"236","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1374-8934","authenticated-orcid":false,"given":"Maria Carmen","family":"Leiva","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine, Sahlgrenska Center for Cancer Research, Institute of Biomedicine, Sahlgrenska Academy University of Gothenburg Gothenburg 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