The risk of breast cancer is significantly increased among obese women as the deleterious adipokines can be over secreted and beneficial adipokines can be hyposecreted. We aim to evaluate the association between obesity-associated adipokines and breast cancer. We searched PubMed, EMBASE, Web of Science, and Chinese Biomedical Literature (CBM) databases for studies reporting association of obesity related adipokines with breast cancer published before Sept. 15, 2015. Initially, 26783 publications were identified, and later, 119 articles were selected for further meta-analysis. Out of these 119 studies, twenty-six studies had reported adipokine levels among obese and non-obese healthy subjects and ninety-three studies had reported adipokine levels among patients with breast cancer. The subjects with BMI >25 kg/m2 had significantly lower adiponectin levels and higher leptin and tumor necrosis factor-α (TNF-α) levels than those with BMI <25 kg/m2. Decreased concentrations of adiponectin, and increased concentrations of leptin, IL-6, IL-8, TNF-α, resistin and visfatin were significantly associated with risk of breast cancer. Adipokine levels were strongly associated with breast cancer among Asian women as compared to non-Asian women. Our results might explain the relationship of obesity, adipokine levels and risk of breast cancer, especially in Asian women.
Multigene panel testing of breast cancer predisposition genes have been extensively conducted in Europe and America, which is relatively rare in Asia however. In this study, we assessed the frequency of germline mutations in 40 cancer predisposition genes, including BRCA1 and BRCA2, among a large cohort of Chinese patients with high hereditary risk of BC. From 2015 to 2016, consecutive BC patients from 26 centers of China with high hereditary risk were recruited (n = 937). Clinical information was collected and next-generation sequencing (NGS) was performed using blood samples of participants to identify germline mutations. In total, we acquired 223 patients with putative germline mutations, including 159 in BRCA1/2, 61 in 15 other BC susceptibility genes and 3 in both BRCA1/2 and non-BRCA1/2 gene. Major mutant non-BRCA1/2 genes were TP53 (n = 18), PALB2 (n = 11), CHEK2 (n = 6), ATM (n = 6) and BARD1 (n = 5). No factors predicted pathologic mutations in non-BRCA1/2 genes when treated as a whole. TP53 mutations were associated with HER-2 positive BC and younger age at diagnosis; and CHEK2 and PALB2 mutations were enriched in patients with luminal BC. Among high hereditary risk Chinese BC patients, 23.8% contained germline mutations, including 6.8% in non-BRCA1/2 genes. TP53 and PALB2 had a relatively high mutation rate (1.9 and 1.2%). Although no factors predicted for detrimental mutations in non-BRCA1/2 genes, some clinical features were associated with mutations of several particular genes.
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Background: In recent years, traditional Chinese medicine (TCM) has been developing rapidly in cancer treatment. Huaier is a widely used fungus by TCM to treat different kinds of cancers. Its good efficacy in prevention of tumor recurrence and metastasis has been proven by a large number of clinical studies. In order to further investigate the efficacy and safety of Huaier granules in post-surgical therapy for stage I-III triple-negative breast cancer (TNBC) patients, we performed a case-control clinical study to observe its effects on the post-surgical safety and survival rates of these patients.Methods: Two hundred and one TNBC patients underwent modified radical mastectomy were selected, they were admitted to our hospital between October 2010 to September 2014. The patients were randomly allocated to the experimental group (101 cases) or the control group (100 cases). Patients in the experimental group were treated with Huaier granules, by orally taking 20 g each time with 3 times a day. Medication was started during chemotherapy or at the time in 6 or 18 months after it. The control group did not receive any TCM preparations during this process. The disease-free survival (DFS) and overall survival (OS) were measured as the main outcome.Results: The median follow-up time was 46 months. For the 100 patients in control group, 5-year DFS and OS was 82% and 86% respectively, while 87.1% and 90.1% for the 101 patients in the experimental group. The difference was not statistically significant. However, stage III patients in the control group showed a 5-year DFS of 53.8% and OS of 65.4%, which were significantly lower than that of stage III patients in the experimental group as 81.3% and 87.5%. In the experimental group, 10 patients with 6-month medication showed disease progression, whereas only 3 patients with 18-month medication showed disease progression. This difference was statistically significant as well.Conclusions: Huaier granules could play an important role in post-surgical adjuvant therapy of TNBC patients, specially by effectively increasing the DFS and OS of breast cancer patients at middle to advanced stage.
Objective: Increasing evidence highlights the roles of N6-methyladenosine (m6A) and its regulators in oncogenesis. Herein, this study observed the associations of m6A regulators with breast cancer.Methods: RNA-seq profiles of breast cancer were retrieved from the Cancer Genome Atlas (TCGA) database. The expression of m6A regulators was analyzed in tumor and normal tissues. Their expression correlations were analyzed by Spearson test. Overall survival (OS) analysis of these regulators was then presented. Gene set enrichment analysis (GSEA) was performed in high and low YTHDF1 expression groups. The correlations of YTHDF1 expression with immune cells and tumor mutation burden (TMB) were calculated in breast cancer samples. Somatic variation was assessed in high and low YTHDF1 expression groups.Results: Most of m6A regulators were abnormally expressed in breast cancer compared to normal tissues. At the mRNA levels, there were closely relationships between them. Among them, YTHDF1 up-regulation was significantly related to undesirable prognosis (p = 0.025). GSEA results showed that high YTHDF1 expression was associated with cancer-related pathways. Furthermore, YTHDF1 expression was significantly correlated with T cells CD4 memory activated, NK cells activated, monocytes, and macrophages. There were higher TMB scores in YTHDF1 up-regulation group than its down-regulation group. Missense mutation and non-sense mutation were the most frequent mutation types.Conclusion: Our findings suggested that dysregulated m6A regulator YTHDF1 was predictive of survival outcomes as well as response to immunotherapy of breast cancer, and were closely related to immune microenvironment.
Background Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, and the targeted therapies are lacking for this type of cancer. We previously demonstrated that Huaier effectively improve 5-year OS and DFS in stage III TNBC patients, and the polysaccharides of Huaier (PS-T) have been identified as the major components of Huaier. However, the mechanisms of anti-tumor action of PS-T is unclear. This study aimed to investigate the effect of PS-T on TNBC cell invasion and migration. Results This study showed that PS-T inhibited cell invasion and migration both in vitro and in vivo by inducing autophagy to suppress epithelial-mesenchymal transition (EMT). Autophagy inhibitor LY294002 or knockdown of ATG5 suppressed the inhibitory effects of PS-T. In addition, as a key transcription factor controlling EMT initiation, Snail was found to be degraded by PS-T induced autophagy. In addition, overexpression of Snail reversed the inhibitory effects of PS-T. Furthermore, it was confirmed that the expression of Snail was inversely correlated with LC3 and associated with poor prognosis using immunohistochemistry and TCGA database analysis, respectively. Conclusions This study demonstrated that PS-T could inhibit EMT in breast cancer cells by inducing autophagy to degrade Snail protein, thus improving the prognosis of TNBC, offering potential treatment alternatives for TNBC patients.
Abstract. Due to lack of systematic reviews, BRCA, DNA Repair Associated (BRCA) mutations in the Chinese population are not completely understood. The following study investigates the prevalence and type of BRCA mutations in Chinese patients with high hereditary risk of breast cancer (BC).Patients Drwere recruited from 14 cities between October 2015 and February 2016, and were selected based on family and personal medical history. BRCA mutations were analyzed by collecting blood samples from all participants. 437 BC patients were included. A total of seventy-six (17.4%) mutation carriers were identified with no geographic difference. The mutation rate in the early-onset BC patients was lower compared to family history of breast/ovarian cancer (OC), bilateral BC, male BC, BC&OC or meeting ≥2 criteria (9.2 vs. 21.7, 24.0, 22.2, 16.7 and 24.3%, respectively, P=0.007). A total of 61 mutation sites were identified (BRCA1 32, BRCA2 29) including 47.5% novel sites and extra 10 variants of uncertain significance. A total of five sites were repeated in more than one unrelated patient. A total of 11 sites were associated with hereditary breast and ovarian cancer syndrome, two of which were confirmed by family pedigrees. Compared with BRCA -patients, patients with BRCA1 mutation tended to be triple-negative BC (P<0.001), whereas patients with BRCA2 mutation were more likely to be hormone receptor positive
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