DEPARTMENT OF COMPARATIVE PATHOBIOLOGY
C. Paige Riley, BS
Graduate Student in Cancer Biology
Department of Comparative Pathobiology
Purdue
University
“Profiling Of And Biomarker Discovery From
Metastatic Breast Cancer Lymphatic Fluid”
Thursday, April 12,
2007
VPTH 112
3:30 pm
Abstract:
Breast cancer is the most common malignant disease,
currently affecting more than 200,000 women in the U.S. It is usually not the primary
tumor, but rather metastases at distant sites that are the main cause of death
of nearly 45,000 of these women per year. In recent years, early detection of
breast cancer by mammographic screening and the use of adjuvant therapy have
helped reduce the rates of breast cancer death.
Unfortunately, the success of chemotherapy has been hampered by multiple
acute, and often long terms, side effects that substantially affect the
patient’s quality of life. Moreover, these problems are compounded by the fact
that it is not currently possible to accurately predict the risk of metastasis
development in individual patients. As a consequence, 80% of women with breast
cancer, with or without metastasis, receive adjuvant therapy. In fact, only
about 40% of these women relapse and ultimately die of metastatic breast cancer
(in spite of aggressive adjuvant therapy), and thus one half of these women are
needlessly ‘over-treated’ and suffer the toxic side effects of chemotherapy and
would have most likely been cure by surgery and radiotherapy alone. Therefore,
new prognostic markers are urgently needed that will allow identification of
patients who are at highest risk for developing metastases. Such markers would
ultimately enable oncologists to begin tailoring treatment strategies to
individual patients. Our central hypothesis is that analysis of lymphatic fluid
draining directly from the tumor will allow the identification of sensitive and
specific protein markers that will accurately reflect individuals most likely
to develop metastatic cancer, and therefore benefit from adjuvant therapy. To determine the validity of our hypothesis
we developed a novel method for collection of lymphatic fluid from the afferent
lymph vessel prior to connection with the sentinel lymph node, and explored the
protein composition of tumor lymph in a rat model for metastases. Our protein profiling approach provides
reproducible global proteomic analysis on lymph and our study shows that the
diseased lymph has a unique protein expression fingerprint which includes
already identified metastatic disease markers such as hemopexin and insulin
like growth factors I and II. This initial proteomic evaluation of the diseased
mammary lymph suggests that lymph is a good source for identification of new
metastases biomarkers to facilitate diagnosis of and therapy for metastatic
cancers. Further assessment of
metastatic vs non metastatic lymph reveals 217 potential biomarkers.