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120 Breast Cancer – Focusing Tumor Microenvironment, Stem Cells and Metastasis

intraductal sampling including samples of nipple aspiration, ductal lavage, and duct endoscopy, is newly used for direct access to the microenvironment surrounding the breast

Serum antigens and autoantibody profiling is another approach for early detection and diagnosis of breast cancer. Elevation in level of two antigens, CA 15-3 and CA 27.29, has been reported. Another way is detection of serum autoantibodies against tumor suppressor genes. Studying the changes appeared in level of several autoantibodies instead of only one

BRCA1/2 mutation or functional losses are the other markers will likely serve as a useful predictive biomarker for diagnosis as well as of response to treatment with PARP inhibitors. REGγ (also known as PA28γ, PSME3 or Ki antigen) is a member of the REG or 11S family of proteasome activators which bind to 20S proteasome and facilitate the related degradation of its intracellular protein substrates. REGγ is one of the potential markers in breast cancer whose expression is associated with breast cancer development and the presence of ER, CerBb-2 and lymph node metastasis. It has been reported that REGγ could facilitate the growth of breast cancer cells. Abnormal high expression of REGγ has been observed in

BCL2 has been introduced as an independent biomarker for prognosis of all types of earlystage breast cancers. Immunohistochemical studies have been introduced BCL2 expression as a new diagnostic instrument in breast cancer studies although further work should be done to ascertain the exact way to apply BCL2 testing for risk estimation and to find a

Ki-67, MI, PCNA, and LI have been reported as markers for poor prognosis, although the most important one has not been established yet (62). Serum associated tumor markers have been newly introduced for breast cancer diagnosis. Carbohydrate antigen (CA) 15-3 and carcinoembryonic antigen (CEA) are the most well-known markers. The noticeable point is that the elevation of CA 15-3 between 4 and 6 weeks after initiation of a new therapy, i.e. spurious early rise (surge), indicates poor prognosis. However, American Society of Clinical Oncology (ASCO) guidelines don't recommend CA 15-3 alone as a marker for either diagnosis or detection of early recurrence of breast cancer. CEA expression level has been not also confirmed as a marker for diagnosis or routine surveillance after primary therapy.

The ASCO recommend CEA level measurement as supplementary information (63).

Overexpression of cathepsin B (CTSB) - which is involved in proteolytic pathways that lead to the degradation of ECM proteins - and caveolin-1 (cav-1) - which is correlated with increased expression of RhoC and resultant increase in cell motility and invasion - have been established in Inflammatory breast cancer (IBC) compared to non-IBC tissues. Furthermore, CTSB expression level has shown a significant positive correlation with the number of positive metastatic lymph nodes in IBC (and not in non-IBC patients). IBC is the most invasive and fatal form of primary breast cancer, the 3-year survival rate for this kind of breast cancer is 40% which compared to 85% for non- IBC, is very poor. Distinct clinical features of this form include a rapid onset, erythema, edema of the breast and a "peaud' orange" appearance of the skin. High metastatic behavior, rapid invasion into blood and lymphatic vessels and formation of tumor emboli within these vessels are also major characteristics of IBC which make this form the most dangerous kind of breast cancer (64). MTDH/AEG-1overexpression or genomic amplification can also be used as biomarker to identify subgroups of patients with requirement for more aggressive treatment, although

cells that are undergoing malignant transformation (59).

antibody appears preferable to achieve more accuracy.

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more studies should be done (40).

standard protocol for BCL2 immunohistochemistry (61).

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**Part 2** 

**Breast Cancer and Microenvironment** 

