One woman out of nine will develop mammary cancer. Though clinical, biochemical and radiological investigation do not reveal tumour spread, haematogenic dissemination often present at the time of diagnosis will be responsible for morbidity and mortality of this disease. The detection of disseminated tumour cells in the blood stream and/or in the bone marrow of breast cancer patients could lead to a better staging and prognostication of these patients.
Immunohistochemical analysis of bone marrow and lymph nodes for the demonstration of morphologically detectable tumour cells has been used since long. This microscopic methodology, however, has a low sensitivity whereby small numbers of tumour cells can be missed. Molecular biology techniques have a much higher sensitivity, yet a low specificity. The aim of this study is to develop a sensitive and specific molecular biological technology to detect micrometastatic disease in breast cancer patients and to compare the results with those obtained by immunohistochemistry.
Tumour cells in peripheral blood and in bone marrow will be detected with RT-PCR amplifying mRNA of cytokeratin-19 (CM19). Using the cDNA sepcific primer/probe set for CK19 and the ABI Prism 7700 Real-Time PCR (TaqmanTM) results will be quantified.
In a second phase of the investigation prognostic significance of these parameters with respect to metastasis and survival in operable breast cancer patients will be addressed.
In a third part of the study the relationship between presence of disseminated tumour cells and tumour angiogenesis will be investigated