Tumor mutational profile of triple negative breast cancer patients in Thailand revealed distinctive genetic alteration in chromatin remodeling gene

Background Triple negative breast cancer (TNBC) is a breast cancer subtype characterized by absence of both hormonal receptors and human epithelial growth factor receptor 2 (HER2). TNBC accounts for 15–20% of breast cancer. TNBC is associated with more aggressive disease and worse clinical outcome. Though the underlying mechanism of TNBC is currently unclear, the heterogeneity of clinical characteristics in various population may relate to the difference in tumor mutational profile. There were studies on TNBC gene mutations in various ethnic groups but the tumor genome data on Thai TNBC patients is currently unknown. This study aims to investigate mutational profile of Thai TNBC. Methods The patients were Thai individuals who were diagnosed with primary breast carcinoma between 2014 and 2017. All surgically removed primary tumor tissues were carefully examined by pathologists and archived as formalin-fixed paraffin-embedded tumor. TNBC was defined by absence of hormonal receptors and HER2 by immunohistochemistry. Genomic DNA was extracted, enriched and sequenced of all exomes on the Illumina HiSeq. Genomic data were then processed through bioinformatics platform to identify genomic alterations and tumor mutational burden. Results A total of 116 TNBC patients were recruited. Genomic analysis of TNBC samples identified 81,460 variants, of which 5,906 variants were in cancer-associated genes. The result showed that Thai TNBC has higher tumor mutation burden than previously reported data. The most frequently mutated cancer-associated gene was TP53 similar to other TNBC cohorts. Meanwhile KMT2C was found to be more commonly mutated in Thai TNBC than previous studies. Mutational profile of Thai TNBC patients also revealed difference in many frequently mutated genes when compared to other Western TNBC cohorts. Conclusion This result supported that TNBC breast cancer patients from various ethnic background showed diverse genome alteration pattern. Although TP53 is the most commonly mutated gene across all cohorts, Thai TNBC showed different gene mutation frequencies, especially in KMT2C. In particular, the cancer gene mutations are more prevalent in Thai TNBC patients. This result provides important insight on diverse underlying genetic and epigenetic mechanisms of TNBC that could translate to a new treatment strategy for patients with this disease

Functional consequence of the MET-T1010I polymorphism in breast cancer.

Major breast cancer predisposition genes, only account for approximately 30% of high-risk breast cancer families and only explain 15% of breast cancer familial relative risk. The HGF growth factor receptor MET is potentially functionally altered due to an uncommon germline single nucleotide polymorphism (SNP), MET-T1010I, in many cancer lineages including breast cancer where the MET-T1010I SNP is present in 2% of patients with metastatic breast cancer. Expression of MET-T1010I in the context of mammary epithelium increases colony formation, cell migration and invasion in-vitro and tumor growth and invasion in-vivo. A selective effect of MET-T1010I as compared to wild type MET on cell invasion both in-vitro and in-vivo suggests that the MET-T1010I SNP may alter tumor pathophysiology and should be considered as a potential biomarker when implementing MET targeted clinical trials

Development and validation of a rapid psychosocial well-being screening tool in patients with metastatic breast cancer

Objective: The aim of this study was to develop and validate a rapid psychosocial well-being screening tool for metastatic breast cancer patients (MBC-PsySoc-Well-being). Methods: Applying a mixed method approach, the study was conducted in two phases. Phase 1, a focus group method was employed for item development, and three focus group sessions were conducted, with patients, caregivers, and medical professionals, respectively. Phase 2, validity and reliability testing were performed. Five experts reviewed items for content validity. Construct validity, criterion-related validity, internal consistency, and test-retest reliability were conducted among a sample of 53 patients with metastatic breast cancer. Results: Six themes were qualitatively analyzed based on focus group participants’ responses. Eight items were then developed based on these themes. The index of Item-Objective Congruence scored by the experts ranged from 0.6 to 1.0. An exploratory factor analysis yielded three factors: Being curious and active in information seeking, Enthusiasm to return to a normal life, and Adjusting to positive lifestyle. The total scores of MBC-PsySoc-Well-being and the European Organization for Research and Treatment of Cancer’s Quality of Life Core Questionnaire (EORTC QLQ-C30) were moderately correlated (r = 0.404, P = 0.003). Cronbach’s α coefficient of the overall scale was 0.686. Pearson correlation coefficients of items between two tests within 14-day ranged from 0.410 to 0.673. Conclusion: This study represents an initiative to develop a rapid psychosocial well-being screening tool for patients with metastatic breast cancer. The results from validity and reliability testing indicate that the scale is moderately suitable for application to patients with metastatic breast cancer. However, a larger scale study should be further administered to confirm the validity and reliability of the measurement