Landscape of clinically actionable mutations in breast cancer ‘A cohort study’

Abstract

Breast cancer (BC) is a heterogeneous disease. Numerous chemotherapeutic agents are available for early stage or advanced/metastatic breast cancer to provide maximum benefit with minimum side effects. However, the clinical outcome of patients with the same clinical and pathological characteristics and treated with similar treatments may show major differences and a vast majority of patients still develop treatment resistance and eventually succumb to disease. It remains an unmet need to identify specific molecular defects, new biomarkers to enable clinicians to adopt individualized treatment for every patient in terms of endocrine, chemotherapy or targeted therapy which will improve clinical outcomes in BC. Our study aimed to identify frequent hotspot mutation profile in BC by targeted deep sequencing in cancer-related genes using Illumina Truseq amplicon/Swift Accel-Amplicon panel and MiSeq technology in an IRB-approved prospective study in a CLIA compliant laboratory. All the cases had pathology review for stage, histological type, hormonal status and Ki-67. Data was processed using Strand NGS™. Mutations identified in the tumor were assessed for ‘actionability’ i.e. response to therapy and impact on prognosis.

Enhancing antioxidant properties of CeO2 nanoparticles with Nd3+ doping: structural, biological, and machine learning insights

“…For example, it has been shown that BC's responses to therapeutic regimens vary due to the diverse genetic profiles among BC cells. 57 In addition, the presence of amino acids, carbohydrates, proteins, and metabolites in different culture media affects the aggregation of NPs and their consequent uptake, toxicity, and bioactivities in cells. 58 Some of these factors can be compared with those of other rare-earth nanostructures (e.g., Gd 2 O 3 , CeO 2 -Gd, and La 2 O 3 ) that are cytotoxic against glioblastoma and hepatoma cell lines.…”

Three-Dimensional Culture Models to Study Innate Anti-Tumor Immune Response: Advantages and Disadvantages

“…In this context, the study of the NK-tumor cell interaction has to consider the dynamic conditions that accompany tumor growth and its vascularization [ 195 , 196 , 197 , 198 ]. It is evident that, within a tumor mass, a strong heterogeneity is present due to the differential expression of altered genes (mutations, up and down regulation of genes, chromosomal/copy number alterations) in different cell populations, and the heterogeneity of the metabolic state of these cells [ 199 , 200 , 201 , 202 , 203 ]. The expression of mutated genes can be dependent on the metabolic state and the primary source of energy used by tumor cells, and vice versa, some mutations trigger metabolic responses [ 204 , 205 , 206 , 207 ].…”

A common goal to CARE: Cancer Advocates, Researchers, and Clinicians Explore current treatments and clinical trials for breast cancer brain metastases

“…Molecular markers, like BRCA1 or BRCA2 (breast cancer gene 1 or 2) germline mutations, are indicators of possible basal-like breast cancer development and are used to determine potential risk and guide treatment 6 . Recent large-scale sequencing efforts have led to the identification of the genes with the highest mutation rates in breast cancer, including TP53 , PIK3CA , AKT1 , PTEN , ERBB2 , ATM , CDH1 , APC , KRAS, NRAS 7 . Ongoing research will determine whether these mutations are “actionable” in order to lay the foundation for personalized medicine approaches.…”