Article
Evaluating Minimal Residual Disease (MRD) in Peripheral Blood of Breast Cancer Patients – Translational Research Program of the SUCCESS-Study
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Published: | March 20, 2006 |
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Background: There isincreasing evidence that MRD in peripheral blood could serve as surrogate marker for risk stratification and predict efficacy and toxicity of cytostatic treatment. As integral part of the SUCCESS-Study, a collaborative project of three German university hospitalsinvestigatesprevalence of and systemic treatment effects on MRD in early breast cancer.
Methods: 60ml of blood will be analyzed for Ca27.29, circulating tumor cells (CTCs), genetic polymorphisms (SNPs) and genetic instability, i.e. loss of heterozygosity (LOH) and microsatelite instability (MSI). After immunomagnetic enrichment with an anti-Epcam-antibody, cells will be labelled with anti-cytokeratin(8,18,19) and anti-CD45 antibodies to distinguish epithelial cells and leukocytes. The CellSearchSystem (Veridex) will be used for isolation and enumeration of cells. Genes coding for targets, transporters and enzymes involved in the metabolism of cytostatics (CYP3A4, CYP2C8, CYP2B6, CYP3A5, CYP2C19, UGT2B7, 5-HT3B) will be analyzed by RT-PCR. PCR-based microsatellite analyses will be performed to identify LOH and MSI at known tumor suppressor genes to determine their influence on tumorigenesis. Analyses will be conducted at Frauenklinik Innenstadt der LMU München, Frauenklinik des Universitätsklinikums Erlangen and Tumorimmunologisches Institut des UKE Hamburg.
Results: The SUCCESS-Study was opened for recruitment on September 15th, 2005. At this point we have analyzed 108 blood samples. Blood samples will be collected at four time points during systemic treatment: before chemotherapy, after the end of chemotherapy and before start of zoledronate/endocrine treatment and after 2 and 5 years of zoledronate/endocrine treatment, respectively. Patients, who show MRD in 2 subsequent blood samples will qualify for intensified metastases screening, including chest x-ray, liver ultrasound and bone scan. First results of detection rates of MRD in peripheral blood will be presented at the meeting.
Conclusions: The combination of a clinical phase III chemotherapy trial with an extensive translational research program will ensure sufficient patient recruitment and high quality monitored clinical data for both aspects. The SUCCESS-Study (www.success-studie.de) will provide information on the role of MRD in peripheral blood for better risk stratification and selection of more individualized treatment options in early breast cancer.
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