Patient Derived Breast Cancer Xenografts
This study will use tissue or body fluid acquired during standard procedures that are part of the patient's care for their cancer, such as surgery to remove tumor tissue or needle withdrawal of body fluid containing cancer cells. The tissue or cells will be injected into immune compromised mice and the tissue will be allowed to grow to a tumor 1-1.5 cm size. The tissue will then be extracted and either frozen, embedded in paraffin, or used for engraftment into another generation of mice. The second generation mice will be separated into groups and given various treatments.
Tissue from the participants and from the mouse established tumors, in which the mice have either received treatment or have not received treatment, will be used to evaluate the levels of various genes that assist in regulating cell growth and cell death. The tumor tissue from participants and mice will also be tested for random changes in the genetic material and compared to the participant's blood to determine if any of the changes in the genetic material correlate with better engraftment of the patient tissue in the mice. It is anticipated that 10-30% will have successful engraftment of tumor tissue
Metastatic Breast Cancer
|Study Design:||Observational Model: Case-Only
Time Perspective: Prospective
|Official Title:||Patient Derived Breast Cancer Xenografts|
- Successful Engraftment [ Time Frame: 2 years ] [ Designated as safety issue: No ]Thirty-five patients with breast cancer will be recruited. We anticipate that 10-30% will have successful engraftment of tumor tissue. The achievement of five successful xenografts would justify additional study.
- Targeted Therapeutic Drugs [ Time Frame: 2 years ] [ Designated as safety issue: No ]To determine which currently available chemotherapeutic agent(s) or targeted therapeutic(s) with reported activity in breast cancer models are most active against an individual patient's tumor growing as a xenograft
- Analysis of relevant downstream signaling pathways. [ Time Frame: 2 years ] [ Designated as safety issue: No ]To assay tumor tissue for putative effectors of clinically relevant downstream signaling pathways as potential biomarkers of response. The immunohistochemical expression of downstream effectors of the mitogen-activated protein kinase (MAPK) and PI3K/AKT/mTOR pathways (p-ERK1/2, p-AKT, p-eIF4E, p-S6) expression will be assessed
- Whole genome DNA sequencing [ Time Frame: 2 years ] [ Designated as safety issue: No ]To identify genomic alterations that correlate with successful human tumor engraftment in mice. Tumor tissue, normal peripheral blood cells, and xenografts which form tumors in mice will evaluated using whole-genome DNA sequencing
Biospecimen Retention: Samples With DNA
whole blood and tumor tissue samples as well as DNA that has been extracted from both blood and tiisue will be stored.
|Study Start Date:||October 2012|
|Estimated Primary Completion Date:||October 2014 (Final data collection date for primary outcome measure)|
|Invasive breast cancer with metastatic disease|
|United States, New Hampshire|
|Dartmouth Hitchcock Medical Center|
|Lebanon, New Hampshire, United States, 03756|
|Principal Investigator:||Gary Schwartz, MD||Dartmouth-Hitchcock Medical Center|