Background: Breast cancer (BC) is a type of disease with high heterogeneity. Molecular profiling, by revealing the intrinsic nature of its various subtypes, has extensively improved the therapeutic management of BC patients. However, the genomic mutation landscape of Chinese metastatic BC has not been fully explored. Methods: Matched plasma and mononuclear cells from 290 Chinese women with metastatic BC were sequenced using either of the two commercially-available panels consisting of 520 cancer-related and 108 BC-related genes. Both panels cover the same critical regions of 91 genes. The circulating tumor DNA mutation profile from our cohort was then compared with publicly-available metastatic BC datasets from Memorial Sloan Kettering Cancer Center (MSKCC) and Pan-cancer analysis of whole genomes (PCAWG). Results: A total of 1,201 mutations spanning 91 genes were detected from 234 patients, resulting in a mutation detection rate of 80.7%. TP53 (64.1%) was the gene with highest mutation frequency, followed by PIK3CA (31%), PTEN (11%), and RB1 (10%). Copy number amplifications (CNAs) in MYC (14.1%), FGFR1 (13.3%), CCND1 (6.6%), FGF3 (6.6%), FGF4 (6.2%) and FGF19 (6.2%) were also detected from our cohort. TP53 mutations were significantly more frequent among triple negative BC (TNBC), HR−/HER2+, and HR+/HER2+ BC, while less common in HR+/HER2-(P < 0.01). Meanwhile, PIK3CA mutations were significantly more frequent among HR+/HER2+, HR+/HER2-, and HR−/HER2+ BC, while less common in TNBC (P < 0.01). Pathogenic or likely pathogenic BRCA1/2 germline mutations were detected in 5.9% of the cohort and 4.4% in TNBC subgroup. Maximum allelic fraction (maxAF) of TP53, RB1, and PIK3CA mutations were associated with multiple organ metastasis. Patients with PIK3CA, PTEN, and RB1 mutation were more likely to have liver metastasis (P < 0.02). Compared with MSKCC and PCAWG dataset, Chinese patients had observably difference in genetic variation rates in different molecular subtypes (TNBC: TP53 73.0 vs. 91.
To investigate the predictive utility of stimulation threshold (ST) of intraoperative electromyography monitoring for facial nerve (FN) outcomes among vestibular schwannoma (VS) patients postoperatively. The authors enrolled 103 unilateral VS patients who underwent surgical resection into a prospective cohort observational study from January 2013 to April 2015 in our hospital. ST values were used to categorize 81 patients into the "low current" (ST ≤ 0.05 mA) group and 22 patients into the control (ST > 0.05 mA) group. The FN function outcomes were summarized and correlated with these two groups at 1, 3, 6, and 12 months after surgery. Binary regression analysis revealed that the percentage of "good" FN outcome, defined by House-Brackmann (HB) classification of facial function (I-II), in the "low current" group was significantly higher than that of the control group (42.0 vs. 4.5% at 1 month, P = 0.015; 64.2 vs. 31.8% at 3 months, P = 0.024; 72.8 vs. 40.9% at 6 months, P = 0.021; 84.0 vs. 45.5% at 12 months, P = 0.002). Ordinal regression analysis showed that the distribution of HB scores was shifted in a favorable direction in the "low current" group at 1, 3, 6, and 12 months postoperatively. For patients with HB IV at the first month postoperative period, the recovery rate of the "low current" group was significantly higher than that of control group (P = 0.003). "Low current" can predict FN function outcomes better and has faster recovery rates than that of the control group.
Background: Sentinel lymph node is the first stop of lymphatic spreading of cancer with known primary. The lymph node metastasis pattern of cancer of unknown primary (CUP) is unclear and has been presumed to follow the same pathway. To test this hypothesis, data of all 716 patients clinically diagnosed as CUP in our center were collected. Methods: Diagnoses of lymph node metastasis were established by 18 F-FDG PET-CT and/or biopsy pathology. Three hundred and forty-seven cases meeting the criteria were divided into three groups: pathology-confirmed primary with invasive biopsy or surgery of the suspicious lesion (group A, n = 64), primary still unknown even with invasive biopsy or surgery of the suspicious lesion (group B, n = 204), and others with no suspicious lesion or lesions who had not been sampled due to medical or other reasons (group C, n = 79). We assessed the clinicopathological features between these groups, and the relationship between lymph node metastasis pattern and confirmed primary site. Results: In group A, the primary sites of 61 cases were compatible with sentinel node theory, resulting in a positive predictive value of 95%. No significant differences in age, sex, bone metastasis, or visceral metastasis observed between group A and group B, except that group A had a higher ratio of differentiated carcinoma (94% vs. 77%, P = 0.003). Conclusion: To our knowledge, this is the first evidence indicating that the majority of clinical CUP cases follow the sentinel node theory to spread in lymph nodes, which helps tracking the primary, especially for differentiated carcinoma.
Background: Programmed death 1 (PD-1)/ programmed death-ligand 1 (PD-L1) inhibitor is one of the most popular immune therapies. Biomarkers for predicting response are highly needed, but no biomarkers are widely used till now. Patients and methods: From February 2018 to April 2019, pan-cancer patients treated with PD-1 or PD-L1 inhibitor as a single agent in our center were included. The benefit group included patients with partial response, complete response and stable disease, while the patients with progressive disease were classified into the nonbenefit group, according to the RECIST 1.1 criteria. Baseline peripheral blood was sampled to determine absolute monocyte count (AMC) and/or classical monocyte frequency (CMF) of peripheral blood mononuclear cells. Then, the association of the above-mentioned two biomarkers with response or progression-free survival (PFS) was evaluated. Results: In total, 107 patients enrolled in the present study. The nonbenefit group had significantly larger number of AMC than benefit group (P<0.001), and patients with higher AMC had decreased PFS time (P=0.001). Of 39 patients tested for CMF, the nonbenefit group had significantly higher CMF than benefit group (P=0.002), and patients with higher CMF had significantly decreased PFS time (P=0.002). The sensitivity of AMC and CMF was 87.9% and 85.7%, respectively, and the specificity was 44.9% and 61.1%, respectively. Multivariate analysis showed high baseline CMF and AMC were both significantly associated with decreased PFS time. Conclusion: Baseline CMF and baseline AMC can be potential pan-cancer biomarkers to predict efficacy of PD-1/PD-L1 inhibitors, especially in the PD-L1 subgroup.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.