In the United States, breast cancer is among the most frequently diagnosed cancers in women. Breast cancer is classified into four major subtypes: human epidermal growth factor receptor 2 (HER2), Luminal-A, Luminal-B, and Basal-like or triple-negative, based on histopathological criteria including the expression of hormone receptors (estrogen receptor and/or progesterone receptor) and/or HER2. Primary breast cancer treatments can include surgery, radiation therapy, systemic chemotherapy, endocrine therapy, and/or targeted therapy. Endocrine therapy has been shown to be effective in hormone receptor-positive breast cancers and is a common choice for adjuvant therapy. However, due to the aggressive nature of triple-negative breast cancer, targeted therapy is becoming a noteworthy area of research in the search for non-endocrine-targets in breast cancer. In addition to HER2-targeted therapy, other emerging therapies include immunotherapy and targeted therapy against critical checkpoints and/or pathways in cell growth. This review summarizes novel targeted breast cancer treatments and explores the possible implications of combination therapy.

BRCA1 and BRCA2 are tumor suppressor genes with pivotal roles in the development of breast and ovarian cancers. These genes are essential for DNA double-strand break repair via homologous recombination (HR), which is a virtually error-free DNA repair mechanism. Following BRCA1 or BRCA2 mutations, HR is compromised, forcing cells to adopt alternative error-prone repair pathways that often result in tumorigenesis. Synthetic lethality refers to cell death caused by simultaneous perturbations of two genes while change of any one of them alone is nonlethal. Therefore, synthetic lethality can be instrumental in identifying new therapeutic targets for BRCA1/2 mutations. PARP is an established synthetic lethal partner of the BRCA genes. Its role is imperative in the single-strand break DNA repair system. Recently, Olaparib (a PARP inhibitor) was approved for treatment of BRCA1/2 breast and ovarian cancer as the first successful synthetic lethality-based therapy, showing considerable success in the development of effective targeted cancer therapeutics. Nevertheless, the possibility of drug resistance to targeted cancer therapy based on synthetic lethality necessitates the development of additional therapeutic options. This literature review addresses cancer predisposition genes, including BRCA1, BRCA2, and PALB2, synthetic lethality in the context of DNA repair machinery, as well as available treatment options.

Chimeric antigen receptor (CAR) T-cell therapy is an innovative form of immunotherapy wherein autologous T-cells are genetically modified to express chimeric receptors encoding an antigen-specific single-chain variable fragment and costimulatory molecules. Moreover, CAR T-cell therapy can only work successfully in patients who have an intact immune system. Therefore, patients receiving cytotoxic chemotherapy will be immunosuppressed making CAR-T therapy less effective. In adoptive CD8+ T-cell therapy (ACT), numerous tumor-specific, engineered T-cells are sourced from patients, expanded in vitro, and infused back expressing tumor-specific antigen receptors. The most successful ACT, anti-CD19 chimeric antigen receptor T-cell therapy directed against B-cell lymphoma, has proved to be efficacious. However, current efforts to utilize this approach for solid tumors, like breast cancer, have shown only modest improvement. Nevertheless, the potential efficacy of CAR-T therapy is promising in an era of immunological advances. By appropriately manipulating CAR T-cells to combat the immunosuppressive forces of the tumor microenvironment, significant eradication of the solid tumor may occur. This review discusses CAR T-cell therapy and its specificity and safety in adoptive cell transfers in breast cancer. We will highlight novel discoveries in CAR T-cell immunotherapy and the formidable barriers including suppression of T-cell function and localization at tumor sites.

Early detection of breast cancer plays a critical role in successful treatment that saves thousands of lives of patients every year. Despite massive clinical data have been collected and stored by healthcare organizations, only a small portion of the data has been used to support decision-making for treatments. In this study, we proposed an engineered up-sampling method (ENUS) for handling imbalanced data to improve predictive performance of machine learning models. Our experiment results showed that when the ratio of the minority to the majority class is less than 20%, training models with ENUS improved the balanced accuracy 3.74%, sensitivity 8.36% and F1 score 3.83%. Our study also identified that XGBoost Tree (XGBTree) using ENUS achieved the best performance with an average balanced accuracy of 97.47% (min = 93%, max = 100%), sensitivity of 97.88% (min = 89% and max = 100%), and F1 score of 96.20% (min = 89.5%, max = 100%) in the validation dataset. Furthermore, our ensemble algorithm identified Cell_Shape and Nuclei as the most important attributes in predicting breast cancer. The finding re-affirms the previous knowledge of the relationship between Cell_Shape, Nuclei, and the grades of breast cancer using a data-driven approach. Finally, our experiment showed that Random Forest and Neural Network models had the least training time. Our study provided a comprehensive comparison of a wide range of machine learning methods in predicting breast cancer risk. It can be used as a tool for healthcare practitioners to effectively detect and treat breast cancer.

Chimeric antigen receptors (CAR) T cells are T cells engineered to express membrane receptors with high specificity to recognize specific target antigens presented by cancer cells and are co-stimulated with intracellular signals to increase the T cell response. CAR-T cell therapy is emerging as a novel therapeutic approach to improve T cell specificity that will lead to advances in precision medicine. CAR-T cells have had impressive outcomes in hematological malignancies. However, there continue to be significant limitations of these therapeutic responses in targeting solid malignancies such as heterogeneous antigens in solid tumors, tumor immunosuppressive microenvironment, risk of on-target/off-tumor, infiltrating CAR-T cells, immunosuppressive checkpoint molecules, and cytokines. This review paper summarizes recent approaches and innovations through combination therapies of CAR-T cells and other immunotherapy or small molecule drugs to counter the above disadvantages to potentiate the activity of CAR-T cells.

This review highlights Receptor Expressed in Lymphoid Tissues (RELT), a Tumor Necrosis Factor Superfamily member, and its two paralogs, RELL1 and RELL2. Collectively, these three proteins are referred to as RELTfms and have gained much interest in recent years due to their association with cancer and other human diseases. A thorough knowledge of their physiological functions, including the ligand for RELT, is lacking, yet emerging evidence implicates RELTfms in a variety of processes including cytokine signaling and pathways that either promote cell death or survival. T cells from mice lacking RELT exhibit increased responses against tumors and increased inflammatory cytokine production, and multiple lines of evidence indicate that RELT may promote an immunosuppressive environment for tumors. The relationship of individual RELTfms in different cancers is not universal however, as evidence indicates that individual RELTfms may be risk factors in certain cancers yet appear to be protective in other cancers. RELTfms are important for a variety of additional processes related to human health including microbial pathogenesis, inflammation, behavior, reproduction, and development. All three proteins have been strongly conserved in all vertebrates, and this review aims to provide a clearer understanding of the current knowledge regarding these interesting proteins.