Study of Biomarkers profile in breast cancer patients

Breast cancer is the most common cancer among female population worldwide.This cancer is a complex phenotypically diverse genetic disease, involving a variety of changes in gene expression and structure. Recent advances in molecular profiling technology have made great progress in unravelling the molecular taxonomy of breast cancer, which has shed new light on the aetiology of the disease and also heralded great potential for the development of novel biomarkers and therapeutic targets. AIM: To identify prognostic biomarkers of long-term outcomes in cancer patients. Methods: Ninety-six nonmetastatic breast cancer patients were included in this study. CTCs(Circutating Tumor Cells) were isolated by immunomagnetic techniques using magnetic beads labelled with a multi-CK-specific antibody (CK3-11D5) and CTC detection through immunocytochemical methods. Estrogen receptor, progesterone receptor and epidermal growth factor receptor (EGFR) were evaluated by immunofluorescence experiments and HER2 and TOP2A by fluorescence in situ hybridization. Results: Baseline detection rate was 48.3% ≥ 1 CTC/30 ml threshold. CTC-positive cells were more frequent in HER2-negative tumors (p = 0.048). In patients younger than 60 years old, HER2-amplified and G1-G2 tumors had a higher possibility of being nondetectable CTCs. Heterogeneous expression of hormonal receptors (HRs) in samples from the same patients was found. Discordances between HR expression, HER2 and TOP2A status in CTCs and their primary tumor were found in the sequential blood samples. Less that 37% of patients switched their CTC status after receiving chemotherapy. EGFR-positive CTCs were associated with Luminal tumors (p = 0.03). Conclusions: Our study suggests that CTC biomarkers profiles might be useful as a surrogate marker for therapeutic selection and monitoring since heterogeneity of the biomarker distribution in CTCs and the lack of correlation with the primary tumor biomarker status were found.About 25% of early breast cancer patients including stage 0 disease can be detected through these biomarkers. The promise of these proteolytic species as early cancer biomarkers and use of the cleavage site-specificantibodies are particularly remarkable, since early breast cancer detection can be applied to establish higher cure rates and thus lead to better prognosis for patients.

کلیدواژه ها:

Breast cancer. Biomarkers ، CTC ، genetic disease