Title |
Blood Test Detects Change from HER2- to+in Breast Cancer
|
Institution |
UNIVERSITY OF TEXAS SW MED CTR/DALLAS, DALLAS, TX
|
Principal Investigator |
UHR, JONATHAN
|
NCI Program Director |
Tracy Lively
|
Cancer Activity |
Diagnostics Research
|
Division |
DCTD
|
Funded Amount |
$253,070
|
Project Dates |
09/01/2005 - 08/31/2008
|
Fiscal Year |
2007
|
Project Type |
Grant
|
Research Topics w/ Percent Relevance |
Cancer Types w/ Percent Relevance |
Genetic Testing (100.0%)
|
Breast (100.0%)
|
Research Type |
Technology and/or Marker Testing in a Clinical Setting
Systemic Therapies - Clinical Applications
|
Abstract |
DESCRIPTION (provided by applicant): This proposal will test the hypotheses that: 1.There is concordance between the HER-2 gene status of metastases and circulating tumor cells (CTCs) in patients with [sic] whose primary tumor was HER-2 gene nonamplified and who acquired HER-2 gene amplification of their CTCs. 2. Such patients can respond significantly better to trastuzumab-containing therapy compared to a control group. At present, patients who acquire HER-2 gene amplification in their CTCs are rarely diagnosed and therefore do not receive needed targeted treatment. This is because the primary tumor is considered the "gold standard" for making the diagnosis of HER-2 gene amplification. This assumption should be questioned because the genetically unstable clone of tumor cells is rapidly mutating giving rise to genetic changes. Clinical experience shows that variants appear which are resistant to the particular chemotherapeutic regimen that was employed. Hence, it would be predicted that amplification of genes that make tumor cells more aggressive and resistant to chemotherapy would emerge with tumor progression. In preliminary experiments involving patients with primary breast carcinoma, concordance between the pathologists' evaluation of the primary tumor and FISH evaluation of CTCs was at the 97% level (29 of 30 patients). Of the breast cancer patients whose primary tumor was HER-2 gene non-amplified, HER-2 gene amplification was present in the CTCs of 37% of such patients (9 of 24) after a recurrence. Four of these patients were treated with trastuzumab-containing therapy. Three patients responded with a PR or CR. Testing of concordance between primary and metastatic tumor with concomitantly obtained CTCs will be extended to 275 patients to obtain statistically significant results. Our oncologists will treat patients who have acquired HER-2 gene amplification in their CTCs with targeted treatment. Finally, a new immunofluorescence method for quantifying HER-2 expression will be studied. The long-term goal is to validate the use of CTCs for determination of changes in immunophenotype and genotype of progressive cancer such as acquisition of HER-2 gene amplification. This would ensure that patients who acquire treatable changes in their tumor will receive optimal targeted therapy. |