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.
What's new?
The prevalence of mutations in breast cancer predisposition genesare not well investigated in Asia. We assessed germline mutations of 40 cancer susceptibility genes in 937 consecutive selected breast cancer patients from 26 centers of China, and discovered 23.8% of participates carried the pathogenic mutation, including 6.8% with mutations in non‐BRCA1/2 genes, while TP53 and PALB2 had a relatively high mutation rates (1.9% and 1.2%).There was no factors predicted for detrimental mutations in non‐BRCA1/2 genes when treated as a whole.
The aim of this study was to investigate the frequency distribution of the cytochrome P450 (
) enzymes,
and
, and the form of tamoxifen metab
ion in premenopausal patients with breast cancer in the ...Han and Uygur ethnic groups of Xinjiang to guide rational clinical drug use. A total of 125 Han patients and 121 Uygur patients with premenopausal hormone-receptor-positive breast cancer treated at the Xinjiang Uygur Autonomous Region Cancer Hospital between 1 June 2011 and 1 December 2013 were selected. The common mutation sites in
were analysed using TaqMan® minor groove binder technology. Genetic testing was performed to determine other metabolic types of tamoxifen, and the genotypes and metabolic types were compared using a Chi-squared test. Between the Han and Uygur groups, there were significant differences in the frequencies of the
(*10/*10) and
(*1/*1) genotypes, with
values of 0.002 and 0.015, respectively. Genotypes of
(*1/*1),
(*1/*5),
(*5/*5),
(*5/*10) and
(*3/*3) were expressed in the two patient groups, and the difference was not statistically significant (
> 0.05). In the Han patients, the proportions of extensive, intermediate and poor metabolisers of tamoxifen were 72, 24 and 4%, respectively, whereas those in the Uygur patients were 76.9, 17.4 and 5.7%, respectively, with no significant difference (
> 0.05). In conclusion, There were partial differences in the
and
gene polymorphisms of
between the Han and Uygur patients with premenopausal breast cancer, but there was no significant difference between the
and
phenotypes. Further research is needed to determine the relationship between the enzyme genetic differences of
and the pharmacokinetics and efficacy of tamoxifen. Although there were some differences in genotypes, these did not result in differences in the predicted tamoxifen metabolisation phenotype between the Han and Uygur patients with breast cancer. Therefore, the doses should be adjusted according to the individual genotype data.
BACKGROUND AND PURPOSE: Breast cancer is now recognized as a clinically heterogeneous disease with a wide spectrum of epidemiological and clinicopathologic features. We aimed to evaluate whether ...epidemiological and clinicopathologic features are associated with the histological tumor grade of breast carcinomas in Western China. METHODS: We retrospectively collected data from the Western China Clinical Cooperation Group and assessed associations between clinicopathologic factors and histological tumor grade in 8619 female breast cancer patients. Patients were divided into two groups: Group I (tumor grade I/II) and Group II (tumor grade III). Univariable analysis and multivariable logistic regression models were used to analyze the relationships between clinicopathologic factors and tumor grade. RESULTS: Patients presenting with positive axillary lymph nodes, large tumor size (>2 cm), lymphovascular invasion, hormone receptor negativity, human epidermal growth factor receptor 2 (HER-2) positivity, and triple negativity tended to have an increased risk of a high tumor grade. However, the number of pregnancies or births was inversely correlated with the risk of a high tumor grade. In addition, patients presenting with grade III tumors were more likely to receive aggressive treatment, such as adjuvant chemotherapy, anti–HER-2 therapy, and level III axillary lymph node dissection. CONCLUSIONS: Our results suggested that several clinicopathologic factors were associated with high tumor grade of breast cancer patients in Western China.
Background and purpose
Limited information is available regarding the correlations between mammographic calcifications and the epidemiological features of patients with breast cancer living different ...lifestyles in Western China. Thus, this study aimed to investigate the relationship between mammographic calcifications and the epidemiological characteristics of female patients with breast cancer in Western China.
Methods
This was a hospital-based, retrospective, multi-center epidemiological study of patients with breast cancer. Using the Western China Clinical Cooperation Group (WCCCG) database, we obtained the records of 7317 patients (with mammographic data) diagnosed with breast cancer between March 2011 and June 2016. These patients were divided into Groups I (mass alone) and II (mass combined with calcification), and their clinical and pathological data were compared.
Results
A total of 4211 patients were enrolled in Group I, and 3106 patients were enrolled in Group II. The tumors in Group II were more likely to be larger (
P
< 0.0001), higher grade (
P
= 0.0029), estrogen receptor (ER)+/progesterone receptor (PR)− (
P
= 0.0319), and human epidermal growth factor receptor 2 (HER-2)-positive (
P
< 0.0001), and to have axillary lymph node metastasis (
P
= 0.0033) than those in Group I. Regarding treatment, patients in Group II were more likely to have undergone chemotherapy (
P
= 0.0108) and anti-HER2 therapy (
P
= 0.0102), whereas patients in Group I were more likely to have undergone endocrine therapy (
P
< 0.0001).
Conclusions
In conclusion, mammographic calcifications in tumors were associated with distinct clinicopathologic characteristics and aggressive treatments.
Overexpression of survivin in breast cancer cells is associated with aberrant inhibition of apoptosis which leads to massive proliferation of cancer cells. Downregulation of survivin by the ...anticancer agent prodigiosin can efficiently induce apoptosis in cancer cells.
The levels of survivin expression in breast cancer stem like side population (SP) cells were assessed. Analyzed were also the rate of apoptosis, drug resistance and the efficiency of clone formation of breast cancer SP cells after treatment with progiosin.
Breast cancer samples contained about 2.7% of cancer stem like SP cells which possessed elevated mRNA expression of stem cell proteins Oct-4, EpCAM and ABC transporter ABCG2, essential for the maintenance of SP cells. Furthermore, the SP cells displayed overexpression of survivin in conjunction with reduced apoptosis and increased multidrug resistance. After treatment with prodigiosin, the SP cells became more sensitive to apoptosis and to several chemotherapeutic agents.
These data suggest that increased expression of survivin in SP cells is one of the major factors involved in apoptosis and resistance to chemotherapy.
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.
What's new?
The prevalence of mutations in breast cancer predisposition genesare not well investigated in Asia. We assessed germline mutations of 40 cancer susceptibility genes in 937 consecutive selected breast cancer patients from 26 centers of China, and discovered 23.8% of participates carried the pathogenic mutation, including 6.8% with mutations in non‐
BRCA1/2
genes, while
TP53
and
PALB2
had a relatively high mutation rates (1.9% and 1.2%).There was no factors predicted for detrimental mutations in non‐
BRCA1/2
genes when treated as a whole.
Germline mutations in PALB2 gene make a small contribution to heritable breast cancer susceptibility. A recent report has revealed that women with mutations in the PALB2 gene were more than nine ...times as likely to develop breast cancer compared to those without. The aim of this study is to understand the status of PALB2 mutations among Chinese high-risk breast cancer patients in a multi-ethnic region in China.
152 patients with hereditary predisposition to breast cancer from the Xinjing region of China were enrolled in the study, and 100 control samples from healthy women were collected in the same locality. We sequenced the coding sequences and flanking intronic regions of PALB2 gene from DNA samples obtained from all subjects by direct sequencing.
A total of 4 deleterious PALB2 mutations were identified in 152 breast cancer patients with a prevalence of about 2.6 % (4/152). The PALB2 mutation prevalence was 3.2 % (3/95) in cases with family history of breast cancer. In addition to the four deleterious mutations, we identified nine missense variants in 12 patients, using the prediction Softwares SIFT and PolyPhen, four of which might be disease associated (in 5 patients). Two of the 4 patients with deleterious mutations and 2 of the 5 patients presenting putative deleterious missense mutations had triple-negative breast cancer. No PALB2 mutation carriers were identified in 100 healthy controls.
PALB2 mutations account for a small, but not negligible, proportion of patients with hereditary predisposition to breast cancer in the Xinjing region of China.
The formation of inclusion in Ti–Al complex deoxidized C–Mn steel was investigated. When Al content in steel is very low(Al=0.0005%), for 0.003%<Ti<0.007%, the inclusion is the ...Al2O3–SiO2–MnO–TiOx composite inclusion; for Ti≥0.009%, the inclusion is TiOx in the steel. When Ti=0.005%, Al<0.001%, the inclusion is the Al2O3–SiO2–MnO–TiOx composite inclusion; while Al>0.006%, inclusions would be pure Al2O3. The experimental results agree with the thermodynamics conclusions.
The screening of BRCA1 and BRCA2 mutations is now an established component of risk evaluation and management of familial breast cancer, early-onset breast cancer and bilateral breast cancer patients. ...There is still some controversy about whether this screening should be done in triple-negative breast cancers. Therefore, we evaluated the BRCA mutation prevalence in patients with triple-negative breast cancer in a multi-ethnic region of China.
A total 96 women who were diagnosed with triple-negative breast cancer in the Xinjiang region of China were enrolled in this study. BRCA1 and BRCA2 screening was performed by polymerase chain reaction-denaturing high-performance liquid chromatography (PCR-DHPLC) sequencing analysis. All mutations were confirmed with direct sequencing.
The prevalence of a BRCA1/2 germline mutation was about 25% (24/96) in the Xinjiang region of China. Among 35 selected cases with a family history and/or bilateral breast cancers, the BRCA1/2 mutation prevalence was 25.7% (9/35). Of the remaining 61 patients with unselected triple-negative breast cancer, the BRCA1/2 mutation prevalence was 24.6% (15/61), and all 15 individuals with these mutations were premenopausal patients.
These results suggest that premenopausal women with triple-negative breast cancer may be candidates for genetic testing for BRCA1/2 in the Xinjiang region of China, even in the absence of a family history or bilateral breast cancer.
The phenomenon of debris flow is intermediate between mass movement and solid transport. Flows can be sudden, severe and destructive. Understanding debris flow erosion processes is the key to ...providing geomorphic explanations, but progress has been limited because the physical-mechanical properties, movement laws and erosion characteristics are different from those of sediment-laden flow. Using infinite slope theory, this research examines the process and mechanism of downcutting erosion over a moveable bed in a viscous debris flow gully. It focuses specifically on the scour depth and the critical slope for viscous debris flow, and formulas for both calculations are presented. Both scour depth and the critical conditions of downcutting erosion are related to debris flow properties （sand volume concentration and flow depth） and gully properties （longitudinal slope, viscous and internal friction angle of gully materials, and coefficient of kinetic friction）. In addition, a series of flume experiments was carried out to characterize the scouring process of debris flows with different properties. The calculated values agreed well with the experimental data. These theoretical formulas are reasonable, and using infinite slope theory to analyze down cutting erosion from viscous debris flow is feasible.
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