Abstract
3283
Purpose: The development of a blood test that can detect cancer or predict disease outcome is an ongoing challenge. One possibility is to use recent knowledge of cancer genetics to develop a simple test applicable to blood samples. The identification of DNA exhibiting tumor specific LOH in plasma from patients with lung and head and neck cancers respectively prompted a wider investigation of other cancer types. Several groups, including our own, identified specific microsatellite alterations, principally LOH, in plasma and/or serum from patients with breast cancer. Moreover, two of these studies suggested that tumor DNA in plasma at diagnosis may be a valuable predictor of disease free-survival The aim of this study was to investigate the utility of plasma DNA analysis for follow up of primary breast cancer patients. Patient and Methods: Blood samples were taken over a period of 2 years following diagnosis from 10 patients with primary breast cancer and over 6 months from 10 patients with metastatic breast cancer . DNA was extracted from lymphocytes, plasma and foci of tumor cells, isolated by laser capture microdissection, and analysed for tumour specific LOH at four loci (DM-1, D17S855, D13S260, D10S249) previously shown to exhibit frequent LOH in breast cancer cases. Double-stranded plasma DNA was also quantified using Pico green fluorescence measurement. Results: All 10 patients who had primary breast cancer had detectable DNA in all plasma samples collected, with variable concentrations but tending to increase with time after diagnosis. 2 had plasma DNA samples taken before breast cancer resection that showed tumor specific alterations (LOH identical to that seen in the tumour). Both of these patients relapsed within 1 year; one has since died and one has developed metastases. The 8 other primary patients remain disease-free 3 years after diagnosis, 5 now show LOH in plasma DNA, which has remained consistent in at least 2 of 3 subsequent plasma samples. The 10 patients with metastatic breast cancer have DNA with consistent tumour specific alterations detected in all plasma samples tested. Conclusions: This pilot study suggests that identifying plasma DNA with LOH at diagnosis in primary patients may be a useful prognostic indicator where there are no other clinical signs of metastatic disease and warrants further investigation in a larger series of patients.
- American Association for Cancer Research