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Breast Cancer: subgroups specific blood-biomarkers for early / predictive diagnosis and personalized treatment

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- Ex vivo sub-cellular imaging of DNA-damage and -repair in circulating leukocytes - Homocystein level in blood-plasma - Pathology-specific protein-profiles in circulating leukocytes
Metabolomics
Genomics
Proteomics
Breast and Gynecologic Cancers Research

Breast-conserving lumpectomy followed by radiation therapy has been shown to be an alternative strategy, competitive to mastectomy, in preventing mortality caused by breast cancer. However, besides negative short-term effects (blood flow disturbances, painful erythema, etc.) breast irradiation causes severe long-term side-effects (leucopenia, anemia, breast edema, fibrosis, increase of angiosarcoma, leukemia, myelodysplastic syndromes). Therefore, the identification of individual susceptibility to radiation and improved patient-specific radiotherapy planning are highly desirable for personalised treatment in breast cancer. Why early and predictive diagnosis is crucial for long-term outcomes of breast cancer? Breast cancer is the most common cause of cancer death among women with an average incidence rate of 10-12 per 100 women. In 2005, breast cancer led to 502,000 deaths worldwide. Advanced stages of breast cancer lead to the development of metastasis predominantly in the lymph nodes, bone, lung, skin, brain, and liver. Although breast-MRI is currently the most sensitive diagnostic tool for breast imaging, its specificity is limited resulting in a negative impact for surgical management in approximately 9 % of cases. Early diagnosis has been demonstrated to be highly beneficial, enabling significantly enhanced therapy efficiency and possibly full recovery.

Some recently developed, advanced diagnostic approaches focus on minimally invasive blood analysis as a valuable source of information concerning individual stress reactions under irradiation treatment. The prognostic role of leukocyte activity in breast cancer patients has long been recognised. Although fluctuating considerably among both node- negative and -positive patients, this activity has been demonstrated to be significantly lower in patients with a greater tumour burden. The authors emphasise the necessity for a more comprehensive analysis that would consider late effects of radiotherapy, stress-response and repair kinetics in terms of diagnostic and prognostic purposes in favour of the personalised treatment of breast cancer patients. In addition to the increased risk of tumour-spreading by invasive biopsies, a serious disadvantage of utilizing biopsy samples for molecular imaging is the mixed cell population obtained, strongly varying from case to case, and resulting in differential gene expression with limited specificity related to the pathology. The central concept of our research in favour to non-invasive diagnosis focuses on 1. blood-tests for the prediction of an individual’s predisposition, 2. highly homogeneous subgroups considering single criteria of patients grouping such as age, familial/genetic predisposition, benign breast pathologies versus malignancy, pre/peri/post-menopausal status, accompanying diseases (e.g. metabolic disorder), etc. 3. combined biomarkers to increase the predictive power of the diagnostic approach.
Measurements of Homocysteine in blood-plasma Measurements of homocysteine in EDTA-plasma were performed using high performance liquid chromatography (HPLC) as described elsewhere. Comet Assay analysis The “Comet assay” provides a simple and effective method for evaluation of DNA damage and DNA-repair capacity in single cells such as leukocytes. The principle of the assay is based upon the ability of DNA fragments to migrate out of the cell under the influence of an electric field. An evaluation of the “comet” tail shape and DNA fragments migration pattern allows for assessment of DNA damage and repair capacity.

There are currently no biomarkers annotated for this protocol.

No datasets are currently associated with this protocol.


New Funding Opportunity: Biomarker Development Laboratories for the Early Detection Network: Applications Due May 23

Update: Pre-application webinar information now available.

The National Cancer Institute's Division of Cancer Prevention has released a new funding opportunity to solicit organ-specific applications for Biomarker Developmental Laboratories (BDLs), one of the four scientific units of the recently funded Early Detection Research Network (EDRN). The EDRN is a national infrastructure funded to discover, develop, and validate biomarkers for risk assessment, detection, and molecular diagnosis and prognosis of early cancer. BDLs are responsible for the discovery, development, characterization, and testing of new, or the refinement of existing, biomarkers and biomarker assays for risk assessment, detection, and molecular diagnosis and prognosis of cancers.

The existing BDLs are primarily focused on ovary and gastrointestinal cancers. The proposed BDLs (to be supported under this funding opportunity) should be focused on one or more of the following cancers: breast, prostate and other genitourinary organs, or lung. In addition, cancers with rapidly rising incidence rates, e.g., endometrial, hepatocellular, kidney, thyroid, oropharyngeal cancers, and/or cancers with unique etiology, e.g., mesothelioma, will be considered.

The newly funded units of the Early Detection Research Network will be announced later in April. Successful applicants have already been notified. Those researchers who were not successful during the last round of applications are encouraged to apply to this opportunity.