HCI-044-EI breast cancer PDX

Tool Details

*FOR RESEARCH USE ONLY (for other uses, please contact the licensing team)

• Research area: Breast Cancer
• Description: Human breast cancer patient-derived xenograft (PDX) model that retains high fidelity to original tumour, including spatial structure, intratumour heterogeneity, genomic features, tumour growth rate, metastatic patterns, and drug responses. These highly translatable PDX models can be used to more accurately assess therapeutic efficacy and predict patient responses in preclinical drug validation studies than traditional models. This panel of PDX models includes some of the deadliest forms of breast cancer such as drug-resistant, metastatic tumours, and endocrine-resistant estrogen receptor-positive (ER+) and human epidermal growth factor receptor positive (HER2+) tumours. Sample taken in 2018 from brain met of Caucasian female, age 43 at time of collection with a primary diagnosis of IDC; 2014 (stage IV with bone mets only). Patient had no previous history of smoking and experienced metastasis in the pleura, bone, and skull. Patient had undergone radiation therapy to the hip 2014; skull and mandible 2015; sacrum and S2 2018 and had received systemic treatment of denosumab 2014; add tamoxifen 2015; taxol 2015; exemestane 2015- 2107; tamoxifen 2017; letrozole, palbociclib 2017-2018; doxorubicin 2018 prior to sample collection. Patient and PDX characteristics were as follows - ER status: positive, PR status: positive, HER2 status: negative. PDX information: PDX engrafted in June 2019 from HCI-044 grown in OVX mice. Not estrogen dependent. PAM50 subtype tests not done and metastasis detected in the brain and liver.

Patient Details

• Cancer: Breast cancer
• Biopsy site: Brain metastasis
• Gender: Female
• Patient ethnicity: Caucasian
• Treatment history: Pretreated: Patient had undergone radiation therapy to the hip 2014; skull and mandible 2015; sacrum and S2 2018 and had received systemic treatment of denosumab 2014; add tamoxifen 2015; taxol 2015; exemestane 2015-2017; tamoxifen 2017; letrozole, palbociclib 2017-2018; doxorubicin 2018 prior to sample collection

Engraftment Details

• Mice passaged: Yes
• Engraftment site: Cleared mammary fat pad
• Host strain: Immunocompromised mice NOD scid gamma (NSG) Jackson Laboratory 5557; NOD/scid, Jackson Laboratory 1303 or NOD rag gamma (NRG), Jackson Laboratory 7799
• Production details: Fresh or thawed human breast tumour fragments were implanted into the cleared inguinal mammary fat pad of female Immune-compromised mice. For bone metastasis samples, bone fragments were coimplanted. For liquid specimens, pleural effusion, or ascites fluid, 1-2 milion cells were injected into cleared mammary fat pads in Matrigel. For ER+ tumours, mice were dosed with E2 beeswax pellets and given supplemental E2 via drinking water. When tumours reached 1-2 cm in diameter, tumours were aseptically collected and reimplanted into new m ice or banked. Estrogen-independent ER+ breast PDX models were generated when ER+ PDX tumours were transplated into overiectomized mice without E2 supplementation.

Handling

• Initial handling information: Implant into the cleared inguinal mammary fat pad of female Immune-compromised mice NSG. NSG (fresh) time to growth: 5 months to 2 cm. Positive ER status
• Additional notes: Additional Information on PDX establishment: https://www.nature.com/articles/s43018-022-00337-6/figures/9

Application Details

• Genetic data: Whole exome sequencing, SNP array, CNV data and RNA sequence from Guillen et al. 2022 Nature Cancer, is available in NIH database dbGaP under accession number phs002479.v1.p1

References

• Tufail, et al. 2024. Journal of Translational Med. Jan 3:22(1):15. PMID: 38172946
• Bhattacharya, et al. 2023. Journal of Experimental & Clinical Cancer Research. Dec 16:42(1):343. PMID: 38102637
• Prekovic, et al. 2023. EMBO Molecular Medicine. Dec 7:15(12):e17737. PMID: 37902007
• Daneshdoust, et al. 2023. Cells. Sep 30:12(19):2338. PMID: 37830602
• Wang, et al. 2023. Cell Bioscience. Dec 1:13(1):224. PMID: 38041134
• Guillen, et al. 2022. Nature Cancer. Feb 3(2):232-250. PMID: 35221336