BRAF Expression and Copy Number Alterations Predict Unfavorable Tumor Features and Adverse Outcomes in Patients With Breast Cancer.

Background: The role of BRAF in breast cancer pathogenesis is still unclear. To address this knowledge gap, this study is aimed at evaluating the impact of BRAF gene expression and copy number alterations (CNAs) on clinicopathologic characteristics and survival in patients with breast cancer. Methods: The Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) dataset was obtained from the cBioPortal public domain. Tumoral BRAF mRNA expression and CNAs along with demographic and tumor data for patients with breast cancer were retrieved. The association of BRAF expression and CNAs with breast cancer clinicopathologic characteristics was analyzed. The impact of BRAF mRNA expression on the overall survival of patients was assessed using Kaplan-Meier survival analysis. Results: BRAF gene mRNA log intensity expression was positively correlated with tumor size and the Nottingham Prognostic Index (NPI) (p < 0.001). Alternatively, BRAF gene expression was negatively correlated with the age at diagnosis (p = 0.003). The average BRAF mRNA expression was significantly higher in premenopausal patients, patients with high tumor grade, hormone receptor-negative status, and non-luminal tumors compared to postmenopausal patients, patients with low-grade, hormone receptor-positive, and luminal disease. BRAF gain and high-level amplification copy numbers were significantly associated with higher NPI scores and larger tumor sizes compared to neutral copy number status. Survival analysis revealed no discernible differences in overall survival for patients with low and high BRAF mRNA expression. Conclusion: High BRAF mRNA expression as well as the gain and high-level amplification copy numbers were associated with advanced tumor characteristics and unfavorable prognostic factors in breast cancer. BRAF could be an appealing target for the treatment of premenopausal patients with hormone receptor-negative breast cancer.

Targeting Receptor Tyrosine Kinases as a Novel Strategy for the Treatment of Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) comprises a group of aggressive and heterogeneous breast carcinoma. Chemotherapy is the mainstay for the treatment of triple-negative tumors. Nevertheless, the success of chemotherapeutic treatments is limited by their toxicity and development of acquired resistance leading to therapeutic failure and tumor relapse. Hence, there is an urgent need to explore novel targeted therapies for TNBC. Receptor tyrosine kinases (RTKs) are a family of transmembrane receptors that are key regulators of intracellular signaling pathways controlling cell proliferation, differentiation, survival, and motility. Aberrant activity and/or expression of several types of RTKs have been strongly connected to tumorigenesis. RTKs are frequently overexpressed and/or deregulated in triple-negative breast tumors and are further associated with tumor progression and reduced survival in patients. Therefore, targeting RTKs could be an appealing therapeutic strategy for the treatment of TNBC. This review summarizes the current evidence regarding the antitumor activity of RTK inhibitors in preclinical models of TNBC. The review also provides insights into the clinical trials evaluating the use of RTK inhibitors for the treatment of patients with TNBC.

Targeting Angiogenesis in Breast Cancer: Current Evidence and Future Perspectives of Novel Anti-Angiogenic Approaches.

Angiogenesis is a vital process for the growth and dissemination of solid cancers. Numerous molecular pathways are known to drive angiogenic switch in cancer cells promoting the growth of new blood vessels and increased incidence of distant metastasis. Several angiogenesis inhibitors are clinically available for the treatment of different types of advanced solid cancers. These inhibitors mostly belong to monoclonal antibodies or small-molecule tyrosine kinase inhibitors targeting the classical vascular endothelial growth factor (VEGF) and its receptors. Nevertheless, breast cancer is one example of solid tumors that had constantly failed to respond to angiogenesis inhibitors in terms of improved survival outcomes of patients. Accordingly, it is of paramount importance to assess the molecular mechanisms driving angiogenic signaling in breast cancer to explore suitable drug targets that can be further investigated in preclinical and clinical settings. This review summarizes the current evidence for the effect of clinically available anti-angiogenic drugs in breast cancer treatment. Further, major mechanisms associated with intrinsic or acquired resistance to anti-VEGF therapy are discussed. The review also describes evidence from preclinical and clinical studies on targeting novel non-VEGF angiogenic pathways in breast cancer and several approaches to the normalization of tumor vasculature by targeting pericytes, utilization of microRNAs and extracellular tumor-associate vesicles, using immunotherapeutic drugs, and nanotechnology.

Pharmacists' experience, competence and perception of telepharmacy technology in response to COVID-19.

BACKGROUND: In the telepharmacy model, the pharmacist can play a pivotal role in delivering pharmaceutical services for patients. However, evidence of pharmacists' impact on improving patient outcomes through disease outbreak through telepharmacy is sparse. OBJECTIVES: This study aims to examine pharmacists' attitudes towards clinical benefits and identify challenges regarding the use of telepharmacy during the COVID-19 pandemic in Jordan. METHOD: A cross-sectional survey design was used to recruit eligible participants from both hospital and community pharmacies. RESULTS: A total of 364 pharmacists agreed to participate in the study. The majority of the participants (70.6%) expressed favourable attitudes towards telepharmacy to accurately capture and report signs and symptoms of COVID-19. Almost 91% agreed that patients can receive immediate medical feedback while using telepharmacy services. Pharmacists (87%) emphasised their role in the monitoring of physiological parameters when entered by patients using telepharmacy technology. However, more than half of the participants reported that lack of reimbursement and evidence-based studies might hinder the use of telemedicine technology to deliver remote clinical services. CONCLUSION: The need for implementing telepharmacy technology has been further boosted because of its noticeable benefits in promoting convenient healthcare services remotely in emergency situations.

Glycosylated Hemoglobin A1c Is Associated with Anthropometric Measurements and Tumor Characteristics in Breast Cancer Patients.

PURPOSE: To investigate the association between glycosylated hemoglobin A1c (HbA1c) with anthropometric measurements and clinicopathologic characteristics of breast cancer patients. Such data are lacking in Arabian countries. PATIENTS AND METHODS: A cross-sectional study was conducted at the Outpatient Oncology Unit at King Hussein Medical Center at the Royal Medical Services (RMS) and 223 breast cancer patients were included. Blood levels of HbA1c were measured and patients were classified into normal/non-diabetic (HbA1c <5.7%), prediabetic (HbA1c 5.7-6.4%), and diabetic (HbA1c ≥6.5%). RESULTS: The average age of patients was 49.9±10.3 years. Most patients had waist circumference equal to or more than 80 cm (91.9%) and more than half (55.2%) had waist-hip ratio equal to or more than 0.85. Mean body mass index (BMI) was 29.9±5.7 kg/m2. The mean level of HbA1c was 6.2±1.4% (range 4.7% to 12.6%). HbA1c levels revealed that most patients in this study classified as prediabetics (44.4%). There was a significant positive correlation between HbA1c levels and each of patient's age (r=0.267, p<0.001), waist circumference (r=0.180, p=0.008), and waist-hip ratio (r=0.278, p<0.001). Compared with premenopausal breast cancer patients, postmenopausal patients had significantly higher HbA1c blood levels (t=-3.542, p=0.003). HbA1c was significantly associated with stage (p=0.044) and grade (p=0.016) of carcinoma in premenopausal breast cancer patients. Among postmenopausal cases, HbA1c was significantly associated with molecular subtype of the disease (p=0.039). CONCLUSION: The majority of Jordanian breast cancer patients in this study are prediabetic, obese, and had visceral obesity. HbA1c levels are increased among older patients and those who have greater waist circumference and waist-hip ratio. HbA1c is associated with advanced stage and grade of breast carcinoma in premenopausal patients and with molecular subtype in postmenopausal cases. These findings urge the need to screen breast cancer patients for glycemic status upon disease presentation and to further consider treatments to control hyperglycemia in order to reduce the impact of metabolic derangements on disease prognosis and outcomes.