الفهرس 
Value of CD73 Expression in Triple Negative Breast Cancer Eligible for Neoadjuvant Chemotherapy
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Abstract
Breast cancer is the most frequent malignancy in women and is a heterogeneous disease on the molecular level. Triple-negative breast cancer (TNBC) is a particularly challenging subtype due to highly invasive nature, relatively low response to therapeutics and dim outcome. Due to absence of specific treatment strategies for this tumor subgroup, TNBC is managed with conventional therapeutics, often leading to systemic relapse and different outcomes, hence a need arises for new markers predicting the outcome of disease course and NACTH response. CD73 is a promising target with controversial role. The aim of this study was to examine the value of CD73 expression in locally advanced triple negative breast cancer tumoral cells as well as tumor infiltrating lymphocytes (TILs) and to elucidate its relation to the extent of NAC response and overall survival of the studied cases. Material and Methods: Seventy nine cases of immunohistochemically confirmed to be triple negative breast carcinoma were evaluated for NACTH response in both tumor and lymph nodes status according to Miller-Payne’s, Sataloff’s systems and residual cancer burden (RCB). CD73 expression in tumor as well as TILs were evaluated in the pre-therapy biopsies, then correlated with NACTH response in breast tumor and lymph nodes, tumor microenvironment (TIL) and special immune cells (FOXP3+ Tregs). Studied parameters were correlated with other clinico-pathological factors and overall survival records. Results: Breast tumors showed high CD73 expression in tumor cells in (49.4%) of cases, high CD73 expression in TILs in (51.9%) of cases . High infiltration by TILs was detected in (60.8%) of cases while high infiltration by FOXP3+Tregs was detected in (36.7%) of cases. High CD73 expression in tumor cells significantly correlates with higher tumor grade, incomplete pCR (Sataloff’s N-C category) in the lymph nodes (p = 0.002), high infiltration by TILS (p=0.001) and high infiltration by FOXP3+ Tregs (p <0.001). Low infiltration by FOXP3+ Tregs was related to partial pathologic response (N-C) in the axillary lymph nodes (P= 0.016), and near complete pCR (Miller grade 4) in the breast tumor (P= 0.017). OS was inversely related to younger age, poor response to neoadjuvant chemotherapy in breast tumor, high infiltration by FOXP3+ Tregs, non-adjuvant therapy intake and CD73 expression in tumor cells and in TILs (P <0.05 each) in the univariate analysis. Multivariate analysis confirmed that high CD73 expression in tumor cells was found to show significant inverse effect on OS (p=0.031). Conclusion: This result may provide evidence that CD73 marker is a good prognostic and predictive marker for TNBC indicated for neoadjuvant chemotherapy and can be used for stratifications of TNBC cases, giving a chance for clinical trials regarding introduction of therapeutic inhibitors targeting CD73 which are already being evaluated at the current time, especially for TNBC cases where target therapeutic regimens are not available due to absent hormonal or Her-2 neu receptors.