Breast cancer (BC) is one of the most widespread malignancies in women worldwide. Breast cancer is mainly classified into a few key molecular subtypes in accordance with hormone and growth factor receptor expression, etc. In spite of numerous advances in the remedy of breast cancer, the development of metastatic disease remains an untreatable and repeated basis of cancer death for women. Preclinical and clinical studies of immunotherapy in cancer remedy have been in progress for the past quite a few decades by an effort to accelerate, augment, and modulate the immune system to spot and devastate cancer cells. Advancement of cancer immunotherapy is rapidly increasing with eminent and most interesting therapy compared to other therapy like targeted therapy, cytotoxic chemotherapy, radiation as well as surgery. Cancer immunotherapy, also known as biological therapy, which denotes the controlling and by means of the patient's own immune system to goal the cancer cells rather than using an extrinsic therapy. In that way, focusing of cancer immunotherapy developing mediators that stimulates or enhances the immune system's recognition and destroying the cancer cells. This review describes a holistic outlook and deeper understanding of the biology of immunotherapy within the system of tumor microenvironment of breast cancer that improve clinical research and constructive impact on the study conclusion.

More than 1 million women worldwide are diagnosed with breast cancer (BC) each year. This study aims to explore the molecular mechanisms of β-catenin affecting the trastuzumab tolerance in HER2-positive BC. β-catenin in BC and non-BC tissue samples were assessed by immunohistochemistry. β-catenin and HER2 were over-expressed and knockdown to evaluate their role in tumorigenicity and trastuzumab resistance in cell and animal models using soft-agar and xenograft assays. Confocal laser immunofluorescence assay and co-immunoprecipitation were used to assess protein-protein binding. Expression of genes was detected using Western blot analysis. β-catenin was highly expressed in primary and metastatic BC, overexpression of β-catenin increased the colony formation of MCF7 cells when it was co-expressed with HER2 and synergically increased the tumor size in immunodeficient mice. Overexpression of β-catenin also increased the phosphorylation of HER2 and HER3 and increased the size of tumor derived from HER2-elevated cells. Confocal laser immunofluorescence assay showed that β-catenin and HER2 were co-localized on the membrane of MDA-MB-231 cells, suggesting that β-catenin binds HER2 to activate the HER2 signaling pathway. Immunoprecipitation of β-catenin and HER2 also confirmed this binding. On the other hand, knockdown of β-catenin in MDA-MB-231 cell lines decreased the activity of SRC and decreased phosphorylation of HER2 at Y877 and Y1248. The interaction between HER2 and SRC was enhanced when β-catenin was overexpressed, and β-catenin increased the resistance of tumor derived from HER2 elevated BT474 cells to trastuzumab. Further analysis showed that trastuzumab inhibited the activation of HER3, but SRC was still highly expressed in cells overexpressing β-catenin. Our work demonstrates that β-catenin is highly expressed in BC and it synergically promotes formation and progress of BC with HER2. β-catenin binds with HER2 leading to enhanced interaction with SRC and resistance to trastuzumab.