18,678 research outputs found
Focal Spot, Winter 2006/2007
https://digitalcommons.wustl.edu/focal_spot_archives/1104/thumbnail.jp
Focal Spot, Winter 2004/2005
https://digitalcommons.wustl.edu/focal_spot_archives/1098/thumbnail.jp
Focal Spot, Summer/Fall 2009
https://digitalcommons.wustl.edu/focal_spot_archives/1112/thumbnail.jp
Focal Spot, Summer/Fall 2004
https://digitalcommons.wustl.edu/focal_spot_archives/1097/thumbnail.jp
The clinical and prognostic use of circulating tumour cells in breast cancer
Adjuvant therapies such as endocrine or cytotoxic chemotherapy have been demonstrated to
improve overall survival in early breast cancer patients. A blood test to monitor patients at risk of
relapse is needed to identify those patients who would benefit from these treatments and those
for whom it is not necessary. This is in favour of detecting disseminated tumour cells (DTCs) from
painful bone marrow aspirates, currently the goldâstandard method for detecting minimal
residual disease (MRD). The use of circulating tumour cells (CTCs) enriched from the blood was
investigated for this purpose along with their characterisation in the metastatic setting to enable
individualised therapy.
Sixtyâfour primary breast cancer patients were followed up for up to 12 years post surgery for
any MRD present. This analysis looked at measurements of DTCs in the bone marrow, CTCs in the
blood and circulatingâfree DNA (cfDNA) in the plasma over the follow up period. Patients who
had involved lymph nodes at surgery, were significantly more likely to have CTCs present than
low risk patients with no nodes positive, (70% compared to 39% respectively, p = 0.042). Our
analysis also looked at the relationship of cfDNA to DTCs and CTCs. An inverse relationship of cell
death in the blood (manifesting as blood cfDNA) to bone marrow DTCs by qRTâPCR was apparent.
This may be due to tumour dormancy mechanisms â cycles of tumour cell proliferation and cell
death occurring in the bone marrow, evidence not shown before in patient samples. Combined
use of these markers could therefore be used as a monitoring system for impending metastatic
disease and a rationale for further treatment.
We also participated in a multiâcentre study to assess the effects of lapatinib; a targeted therapy
against two members of the human epidermal growth factor receptor family (EGFR and HER2).
This was in advanced breast cancer patients and used CTCs as a surrogate marker. Our study
selected patients on the basis of EGFR positivity in CTCs that were present in the blood. Four out
of 12 patients (33%) demonstrated an initial decrease in the number of EGFR positive CTCs in
response to Lapatinib, however this was limited and all patients were taken off study with
progressive disease. We also explored a novel method in development to detect viable CTCs. This
used an in situ hybridisation method to amplify signals from mRNA transcripts of tumour markers
in CTCs. The use of CTCs is a very useful and promising tool for studying both the biology of
breast cancer, and also as a nonâinvasive analytical tool in the clinical setting to gain predictive
and prognostic information
Immunoscintigraphy for therapy decision making and follow-up of biological therapies
With the availability of new biological therapies there is the need of more accurate diagnostic tools to noninvasively
assess the presence of their targets. In this scenario nuclear medicine offers many radiopharmaceuticals for
SPECT or PET imaging of many pathological conditions. The availability of monoclonal antibodies provides tools to
target specific antigens involved in angiogenesis, cell cycle or modulation of the immune systems. The radiolabelling of
such therapeutic mAbs is a promising method to evaluate the antigenic status of each cancer lesion or inflamed sites
before starting the therapy. It may also allow to perform follow-up of such biological therapies. In the present review we
provide an overview of the most studied radiolabelled antibodies for therapy decision making and follow-up of patients
affected by cancer and other pathological conditions
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