Clinical Utility of Breast Cancer DNA Markers in Serum
Creators: name: University Of California Office Of The President
Publisher: name: University of California Office of the President
publisherIdentifier: https://ror.org/00dmfq477
publisherIdentifierScheme: ROR
Year: 2024

description: The incidence of early stage breast cancer is rapidly increasing due to advances in methods for its detection. Despite these improvements 20-30% of patients without evidence of metastatic disease at initial diagnosis will subsequently develop a recurrence. New methods to identify high-risk patients requiring aggressive adjuvant therapy and to those not requiring treatment are needed. Because cancer progression has been shown to result from the accumulation of genetic alterations within the cell, assays that identify these genetic events may serve as valuable prognostic indicators. However, studies evaluating tumors are limited as they assess only a single time-point in the disease course and require a biopsy, an invasive procedure that may be associated with potential morbidity. Also this method is not always practical for early stages of disease when detection may be critical. We have recently developed an assay that can identify tumor-associated genetic aberrations from a patient's blood sample. We have demonstrated that these circulating genetic marker alterations correlate with those occurring in the patient's tumors and thus may act as surrogate markers of disease.
 
 
 
 
 
 
 
 Our hypothesis is that the sensitive genetic marker assay of serum will permit a minimally invasive approach to assess those genetic changes that may occur during tumor progression, and their assessment will have prognostic implications. We hypothesize that the serum genetic marker assay will allow earlier detection of breast cancer disease progression and identify disease-free patients who are likely to have disease recurrence within a short time.
 
 
 
 
 
 
 
 We have developed a method to isolate "free" DNA from small amounts of blood and analyze the DNA for tumor genetic markers. The DNA markers are amplified and assessed using highly sensitive instrumentation. In addition to assessing blood, we will also analyze bone marrow. We will develop an array of genetic markers that are frequently found in breast tumors. These markers will then be used to assess blood (serum) isolated from patients taken both before and after surgery. Bone marrow will be assessed as blood is for DNA markers. We focus our efforts on early stage patients, particularly those undergoing sentinel Iymph node mapping, a technique used to identify early disease spreading to the tumor-draining Iymph nodes.
 
 
 
 
 
 
 
 In this proposal one of the innovative approaches will be to use a more robust, rapid, high-throughput, and sensitive instrumentation to improve the assay efficacy.. The unique element of this proposal is that it permits a comprehensive approach for screening early stage breast cancer patients by using highly sensitive techniques for assessing critical sites of early disease spreading: sentinel lymph node(s), blood, and bone marrow. These findings may prove highly predictive of disease recurrence and help staging disease. Finally, more appropriate patient stratification into clinical treatment protocols may occur earlier in the disease course as a consequence of these genetic based tests. This addition of molecular oncology to current clinical and radiographic evaluations for disease screening and diagnosis may prove beneficial in the overall care of breast cancer patients in California.