Effects of neoadjuvant therapies on genetic regulation of targeted pathways in ER+ primary ductal breast carcinoma: A meta-analysis of microarray datasets

Abstract

Breast cancer arises as a result of multiple interactions between environmental and genetic factors. Conventionally, breast cancer is treated based on histopathological and clinical features. DNA technologies like the human genome microarray are now partially integrated into clinical practice and are used for developing new “personalized medicines” and “pharmacogenetics” for improving the efficiency and safety of cancer medications. We investigated the effects of four established therapies—for ER+ ductal breast cancer—on the differential gene expression. The therapies included single agent tamoxifen, two-agent docetaxel and capecitabine, or combined three-agents CAF (cyclophosphamide, doxorubicin, and fluorouracil) and CMF (cyclophosphamide, methotrexate, and fluorouracil). Genevestigator 8.1.0 was used to compare five datasets from patients with infiltrating ductal carcinoma, untreated or treated with selected drugs, to those from the healthy control. We identified 74 differentially expressed genes involved in three pathways, i.e., apoptosis (extrinsic and intrinsic), oxidative signaling, and PI3K/Akt signaling. The treatments affected the expression of apoptotic genes ( TNFRSF10B [ TRAIL ], FAS , CASP3/6/7/8 , PMAIP1 [ NOXA ], BNIP3L , BNIP3 , BCL2A1 , and BCL2 ), the oxidative stress-related genes ( NOX4 , XDH , MAOA , GSR , GPX3 , and SOD3 ), and the PI3K/Akt pathway gene ( ERBB2 [ HER2 ]). Breast cancer treatments are complex with varying drug responses and efficacy among patients. This necessitates identifying novel biomarkers for predicting the drug response, using available data and new technologies. GSR , NOX4 , CASP3 , and ERBB2 are potential biomarkers for predicting the treatment response in primary ER+ ductal breast carcinoma.

Combinations of Calcitriol with Anticancer Treatments for Breast Cancer: An Update

“…Notably, other BC subtypes such as ER-positive, PR-positive, and HER2-positive also express VDR in a high percentage of tumor cells, a feature found to be associated with more favorable prognostic characteristics and less aggressive phenotypes [ 47 ]. The choice of treatment in each of these cases is based on tumor histopathological features, molecular markers and clinical characteristics, and may include chemotherapy in conjunction with a targeted therapy [ 48 , 49 ]. Therefore, given the high rate of VDR expression in BC tumors, it is feasible to target this receptor in conjunction with chemotherapeutic drugs in the different BC subtypes.…”

Comprehensive analysis of gene expression profiles to identify differential prognostic factors of primary and metastatic breast cancer

“…Breast cancer (BC), which is the most frequently diagnosed cancer type in women, could be treatable if detected in its early stages ( Andreopoulou and Hortobagyi, 2008 , Jemal et al, 2009 , OZKAN, 2022 , Masood, 2005 , Albogami et al, 2021 ). Based on its stage, the prognosis of BC is usually classed from I to IV, with various sub-stages( Cianfrocca and Goldstein, 2004 ).…”