Breast Cancer In Chinese Women Research Articles

Guidelines for clinical diagnosis and treatment of advanced triple negative breast cancer in China（2024 edition）

Breast cancer ranks as the most common female malignancy worldwide. Data from GLOBOCAN 2020 showed that breast cancer surpassed lung cancer and become the leading malignancy globally which was a serious threat to women's health. Different from Caucasian, there is a lower prevalence of breast cancer in Chinese women. But the age-standardized incidence rate of breast cancer in China has reached to 39.1 per 100,000 in 2020, with 416,000 new cases, accounting for 18.4% of global breast cancer burden, due to multiple factors such as lifestyle and dietary habits changes in recent years[1]. The treatment and prevention of breast cancer are becoming increasingly a tuff task. In addition, triple-negative breast cancer (TNBC) is a subtype with higher malignancy and worse prognosis. Due to lack of specific therapeutic targets, less treatment progress has been made in recent years. There is even less progress in the therapy of advanced TNBC, but huge unmet needs exist for further therapeutic optimization. Echoing advocacy from The Society of Breast Cancer China Anti-Cancer Association; International Medical Exchange Society, Chinese Anti-Cancer Association; Breast Cancer Group, Branch of Oncologist, Chinese Medical Doctor Association, top experts from multidisciplinary departments of breast cancer in China have consensus on this "Guidelines for Clinical Diagnosis and Treatment of Advanced Triple-Negative Breast Cancer in China (2024 Edition)" according to the latest evidence based updates. We hope this pater can guide or optimize the precise therapeutic decision-making for advanced triple-negative breast cancer in China.

Association between prolactin/testosterone ratio and breast cancer in Chinese women.

Association between prolactin/testosterone ratio and breast cancer in Chinese women.

CYP4B1 polymorphisms and the risk of breast cancer in Chinese women: a case-control study

BackgroundBreast cancer (BC) is one of the malignant diseases threatening the life and health of women worldwide. The CYP4B1 gene was abnormally expressed in BC and was associated with the prognosis of BC patients. This study aimed to explore the relationship between CYP4B1 single nucleotide polymorphisms (SNPs) and BC risk in Chinese women.MethodsA case-control study of 1,143 women (571 patients and 572 healthy individuals) was conducted. Rs2297813 G/T, rs12142787 G/A, and rs3766197 C/T in CYP4B1 were selected and genotyped by MassARRAY system. The relationships between these SNPs and the risk of BC were assessed by logistic regression analysis. In addition, multi-factor dimensionality reduction (MDR) was used to analyze SNP-SNP interactions.ResultsCYP4B1 rs2297813 had a risk-increasing effect on BC in women with body mass index (BMI) ≤ 24 kg/m2 (OR = 1.72, p = 0.026). CYP4B1 rs12142787 was associated with an increased BC risk in smokers (AA: OR = 1.32, p = 0.045). Among non-drinkers, rs2297813 (OR = 1.69, p = 0.009) and rs12142787 (OR = 1.51, p = 0.020) were related to an increased incidence of BC. CYP4B1 rs3766197 (OR = 1.61p = 0.031) was associated with a higher risk of advanced stages (III/IV stage) of BC. Besides, the contributions of CYP4B1 rs2297813 (OR = 1.55, p = 0.021) and rs12142787 (OR = 1.53, p = 0.033) to BC risk might be associated with more than one birth in patients with BC. The three-locus model consisting of rs2297813, rs12142787, and rs3766197 was regarded as the best predictive model for BC risk.ConclusionCYP4B1 SNPs were associated with BC risk in Chinese women, especially in patients with BMI ≤ 24 kg/m2, smokers, non-drinkers, patients in advanced stages (III/IV stage), and patients who reproduced once. These findings shed light on the relationship between CYP4B1 SNPs and BC risk in Chinese women.

Spatial pattern and environmental drivers of breast cancer incidence in Chinese women.

Breast cancer (BC) had the highest incidence of all cancers in Chinese women. However, studies on spatial pattern and environmental drivers of BC were still lacked as they were either limited in a small area or few considered the comprehensive impact of multiple risk factors. In this study, we firstly performed spatial visualization and the spatial autocorrelation analysis based on Chinese women breast cancer incidence (BCI) data of 2012-2016. Then, we explored the environmental drivers related to BC by applying univariate correlation analysis and geographical detector model. We found that the BC high-high clusters were mainly distributed in the eastern and central regions, such as Liaoning, Hebei, Shandong, Henan, and Anhui Provinces. The BCI in Shenzhen was significantly higher than other prefectures. Urbanization rate (UR), per capita GDP (PGDP), average years of school attainment (AYSA), and average annual wind speed (WIND) had higher explanatory power on spatial variability of the BCI. PM10, NO2, and PGDP had significant nonlinear enhanced effect on other factors. Besides, normalized difference vegetation index (NDVI) was negatively associated with BCI. Therefore, high socioeconomic status, serious air pollution, high wind speed, and low vegetation cover were the risk factors for BC. Our study may able to provide evidence for BC etiology research and precise identification of areas requiring focused screening.

The association between CTSZ methylation in peripheral blood and breast cancer in Chinese women.

Previous studies have shown that DNA methylation in peripheral blood may be associated with breast cancer (BC). To explore the association between the methylation level of the Cathepsin Z (CTSZ) gene in peripheral blood and BC, we conducted a case-control study in the Chinese population. Peripheral blood samples were collected from 567 BC cases, 635 healthy controls, and 303 benign breast disease (BBD) cases. DNA extraction and bisulfite-specific PCR amplification were performed for all samples. The methylation levels of seven sites of the CTSZ gene were quantitatively determined by Mass spectrometry. The odds ratios (ORs) of CpG sites were evaluated for BC risk using per 10% reduction and quartiles analyses by logistic regression. Our analysis showed that five out of the seven CpG sites exhibited significant associations with hypomethylation of CTSZ and BC, compared to healthy controls. The highest OR was for Q2 of CTSZ_CpG_1 (OR: 1.62, P=0.006), particularly for early-stage breast cancer in the case of per 10% reduction of CTSZ_CpG_1 (OR: 1.20, P=0.003). We also found that per 10% reduction of CTSZ_CpG_5 (OR: 1.39, P=0.004) and CTSZ_CpG_7,8 (OR: 1.35, P=0.005) were associated with increased BC risk. Our study also revealed that four out of seven CpG sites were linked to increased BC risk in women under 50 years of age, compared to healthy controls. The highest OR was for per 10% reduction of CTSZ_CpG_1 (OR: 1.47, P<0.001). Additionally, we found that BC exhibited lower methylation levels than BBD at CTSZ_CpG_4 (OR for Q1: 2.18, P<0.001) and CTSZ_CpG_7,8 (OR for Q1: 2.01, P=0.001). Furthermore, we observed a correlation between methylation levels and tumor stage, ER, and HER2 status in BC patients. Overall, our findings suggest that altered CTSZ methylation levels in peripheral blood may be associated with breast cancer, particularly in young women, and may serve as a potential biomarker for early-stage BC.

A nomogram based on genotypic and clinicopathologic factors to predict the non-sentinel lymph node metastasis in Chinese women breast cancer patients.

Sentinel lymph node biopsy (SLNB) is the standard treatment for breast cancer patients with clinically negative axilla. However, axillary lymph node dissection (ALND) is still the standard care for sentinel lymph node (SLN) positive patients. Clinical data reveals about 40-75% of patients without non-sentinel lymph node (NSLN) metastasis after ALND. Unnecessary ALND increases the risk of complications and detracts from quality of life. In this study, we expect to develop a nomogram based on genotypic and clinicopathologic factors to predict the risk of NSLN metastasis in SLN-positive Chinese women breast cancer patients. This retrospective study collected data from 1,879 women breast cancer patients enrolled from multiple centers. Genotypic features contain 96 single nucleotide polymorphisms (SNPs) associated with breast cancer susceptibility, therapy and prognosis. SNP genotyping was identified by the quantitative PCR detection platform. The genetic features were divided into two clusters by the mutational stability. The normalized polygenic risk score (PRS) was used to evaluate the combined effect of each SNP cluster. Recursive feature elimination (RFE) based on linear discriminant analysis (LDA) was adopted to select the most useful predictive features, and RFE based on support vector machine (SVM) was used to reduce the number of SNPs. Multivariable logistic regression models (i.e., nomogram) were built for predicting NSLN metastasis. The predictive abilities of three types of model (based on only clinicopathologic information, the integrated clinicopathologic and all SNPs information, and integrated clinicopathologic and significant SNPs information) were compared. Internal and external validations were performed and the area under ROC curves (AUCs) as well as a series of evaluation indicators were assessed. 229 patients underwent SLNB followed by ALND and without any neo-adjuvant therapy, 79 among them (34%) had a positive axillary NSLN metastasis. The LDA-RFE identified the characteristics including lymphovascular invasion, number of positive SLNs, number of negative SLNs and two SNP clusters as significant predictors of NSLN metastasis. Furthermore, the SVM-RFE selected 29 significant SNPs in the prediction of NSLN metastasis. In internal validation, the median AUCs of the clinical and all SNPs combining model, the clinical and 29 significant SNPs combining model, and the clinical model were 0.837, 0.795 and 0.708 respectively. Meanwhile, in external validation, the AUCs of the three models were 0.817, 0.815 and 0.745 respectively. We present a new nomogram by combining genotypic and clinicopathologic factors to achieve higher sensitivity and specificity comparing with traditional clinicopathologic factors to predict NSLN metastasis in Chinese women breast cancer. It is recommended that more validations are required in prospective studies among different patient populations.

The Chinese Version of the Breast Cancer Literacy Assessment Tool: Translation, Adaptation, and Validation Study.

Breast cancer is the most common cancer among Chinese women, with an age-standardized prevalence of 21.6 cases per 100,000 women. Limited cancer health literacy reduces females' ability to engage in cancer prevention and detection. It is necessary to assess Chinese women's breast cancer literacy to deliver targeted interventions and effective education. However, there is no Breast Cancer Literacy Assessment Tool (B-CLAT) available in China currently. This study aimed to translate and linguistically and culturally adapt the B-CLAT into a simplified-Chinese version (C-B-CLAT), and then validate its psychometric properties by administering it to Chinese college students. First, we translated the B-CLAT into a simplified-Chinese version and verified its validity and reliability using rigorous translation and validation guidelines proposed in previous studies. We then evaluated the psychometric properties among 50 female participants with a mean age of 19.62 (SD 1.31) years recruited from Nantong University, China. Items 1, 6, 8, 9, 10, 16, 17, 20, 21, 22, 23, 24, 25, 26, 29, and 30 were deleted to increase the relevant subscale internal consistency. Items 3, 12, 13, 14, 18, 20, 27, and 31 were deleted due to their Cronbach α being lower than .5 in the test-retest analysis. After deletion, the internal consistency of the entire scale was fair with α=.607. The prevention and control subscale had the highest internal consistency with α=.730, followed by the screening and knowledge subscale with α=.509, while the awareness subscale had the lowest internal consistency with α=.224. The intraclass correlation coefficient for the C-B-CLAT (items 2, 4, 5, 7, 11, 15, 28, 32, 33, and 34) was fair to excellent (odds ratio [OR] 0.88, 95% CI 0.503-0.808). The values of Cronbach α for items 2, 4, 5, 7, 11, 15, 28, 32, 33, and 34 ranged from .499 to .806, and the α value for the C-B-CLAT was .607. This indicates fair test-retest reliability. The mean difference in the C-B-CLAT scores between stage 1 and stage 2 was 0.47 (OR 0.67, 95% CI -0.53 to 1.47), which was not significantly different from zero (t48=0.945; P=.35). This result implies that the C-B-CLAT produced the same scores at stage 1 and stage 2 on average, thus showing good agreement in the C-B-CLAT scores between stage 1 and stage 2. The SD of the difference was 3.48. The 95% limits of agreement were -6.34 to 7.28. We developed a simplified-Chinese version of the B-CLAT through translation and adaptation. Psychometric properties testing has proven this version valid and reliable for assessing breast cancer literacy among Chinese college students.

Impact of MIR31HG polymorphisms on risk of breast cancer in Chinese women

Breast cancer (BC) is one of the leading causes of death worldwide. This study explored the relationship between the MIR31HG gene polymorphisms and the risk of BC in Chinese women. Eight single nucleotide polymorphisms (SNPs) in MIR31HG were genotyped among 545 patients with BC and 530 healthy controls using Agena MassARRAY analysis. The PLINK software was used to calculate the odds ratio (OR) and 95% confidence intervals (CIs) via the logistic regression analysis. Multi-factor dimensionality reduction (MDR) analysis was performed to study the impact of SNP-SNP interaction on BC risk. MIR31HG rs72703442-AA (OR 0.29, 95% CI 0.10-0.79, p = 0.026), rs55683539-TT (OR 0.46, 95% CI 0.26-0.80, p = 0.012) and rs2181559-AA (OR 0.59, 95% CI 0.40-0.89, p = 0.038) were associated with a reduced risk of BC in Chinese women, as well as stratified results at age ≥ 52years. Rs79988146 was correlated with estrogen receptor (ER) and progesterone receptor (PR)in Chinese female BC patients under various genetic models. Age at menarche stratification indicated that rs1332184 was associated with increased risk in BC patients, whereas stratification by number of births indicated that rs10965064 was associated with reduced risk in BC patients. MDR analysis showed that the best single-locus model for predicting of BC risk are rs55683539, which, rs55683539-CC group was a high risk group and rs55683539-TT group was a low risk group. The results indicated that the MIR31HG polymorphisms were associated with a reduced risk of BC in Chinese women.

Analysis on Incidence and Mortality Trends and Age–Period–Cohort of Breast Cancer in Chinese Women from 1990 to 2019

To analyze the incidence and mortality trends of breast cancer among women in China from 1990 to 2019 and explore the effects of age, period, and cohort on the incidence and mortality of breast cancer. We performed a Joinpoint regression model to describe trends in breast cancer incidence and mortality. We used an age-period-cohort analysis model to estimate the impact of age, period, and cohort on breast cancer incidence and mortality. We collected breast cancer incidence and mortality among women aged 20-89 in China (1990-2019) from the Global Health Data Exchange (GHDx) database. The crude incidence and mortality of breast cancer from 1990 to 2019 in Chinese women showed an increasing trend, with an average annual increase percentage (AAPC) of 4.69% and 2.18%, respectively. The analysis on the age-period-cohort model revealed that the risk of incidence increased first and then decreased with age and peaked at 55-59 years old, whereas the risk of mortality increased by approximately 60.34 times from 20 to 89 years old. The risk of incidence and mortality increased by 2.64 and 1.49 times with the passage of time, respectively. The later the birth cohort is, the lower the risk of incidence and mortality will be. From 1990 to 2019, the incidence and mortality of breast cancer among Chinese women showed an increasing trend, and the prevention and control situation of breast cancer was still grim. Therefore, visual examination and palpation examination should be actively carried out in adult women with breast cancer, and the conventional population after 40 years of age, the high-risk population carrying hereditary breast cancer gene and the elderly population should be assisted with imaging examination along with palpation examination. When treating patients suffering from breast cancer, in order to reduce the death rate, a personalized treatment plan should be developed based on the characteristics of different patients.

Association between KRAS gene polymorphisms and genetic susceptibility to breast cancer in a Chinese population.

The KRAS gene has a pathophysiological role in the development of many cancers. This study aims to investigate the relationship between KRAS polymorphisms and genetic susceptibility to breast cancer. The rs712, rs12587 and rs9266 gene loci in the KRAS gene of 421 subjects (141 breast cancer patients, 141 benign breast tumours and 139 healthy controls) were analysed by the polymerase chain reaction and SNaPshot sequencing. Transcriptomic information on KRAS and corresponding clinical information was downloaded from the TCGA and GTEx databases. Differences in KRAS expression between breast cancer tissues and control tissues were analysed. We found no significant association between KRAS rs712 and rs12587 locus gene polymorphisms and an increased risk of developing benign breast tumours and breast cancer (p > 0.05). The KRAS rs9266 locus mutation heterozygous model CT and dominant model CT + TT were significantly associated with an increased risk of breast cancer (both p < 0.05). In addition, the TAT haplotype was expressed at an increased frequency, and the GAC haplotype was expressed at a reduced frequency in breast cancer compared with controls (both p < 0.05). We found that KRAS was over expressed in breast cancer tumour tissues compared with the control tissues (p < 0.0001). The KRAS rs9266 gene polymorphism and the TAT haplotype may be associated with an increased risk of breast cancer in Chinese women. The GAC haplotype may be a protective factor against breast cancer.

Perfluoroalkyl substances (PFASs) as risk factors for breast cancer: a case–control study in Chinese population

BackgroundPerfluoroalkyl substances (PFASs) are a large family of synthetic chemicals, some of which are mammary toxicants and endocrine disruptors. Recent studies have implicated exposure to PFASs as a risk factor for breast cancer in Europe and America. Little is known about the role of PFASs with respect to breast cancer in the Chinese population.MethodsParticipants who were initially diagnosed with breast cancer at Tianjin Medical University Cancer Institute and Hospital between 2012 and 2016 were recruited as cases. The controls were randomly selected from the participants with available blood samples in the Chinese National Breast Cancer Screening Program (CNBCSP) cohort. Ultimately, we enrolled 373 breast cancer patients and 657 controls. Plasma PFASs were measured by an ultra-performance liquid chromatography (UPLC) system coupled to a 5500 Q-Trap triple quadrupole mass spectrometer. A logistic regression model with least absolute shrinkage and selection operator (LASSO) regularization was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) to assess the relationships between PFASs and breast cancer. The three most predictive variables in the LASSO model were selected from 17 PFASs, which was based on the optimal penalty coefficient (λ = 0.0218) identified with the minimum criterion. Additionally, Bayesian kernel machine regression (BKMR) and quantile g-computation models were applied to evaluate the associations between separate and mixed exposure to PFASs and breast cancer.ResultsPerfluorooctanesulfonic acid (PFOS) exhibited the highest concentration in both the cases and controls. Perfluorooctanoic acid (PFOA) and perfluoro-n-decanoic acid (PFDA) were positively associated with breast cancer, and perfluoro-n-tridecanoic acid (PFTrDA) was negatively associated with breast cancer according to both the continuous-PFASs and the quartile-PFASs logistic regression models. Of note, PFOA was associated with the occurrence of estrogen receptor (ER)-, progesterone receptor (PR)-, and human epidermal growth factor receptor 2 (HER2)-positive breast cancer (ORER+ = 1.47, 95% CI: 1.19, 1.80; ORPR+ = 1.36, 95% CI: 1.09, 1.69; ORHER2 = 1.62, 95% CI: 1.19, 2.21).ConclusionsOverall, we observed that PFASs were associated with breast cancer in Chinese women. Prospective cohort studies and mechanistic experiments are warranted to elucidate whether these associations are causal.

A comprehensive comparison of circulating tumor cells and breast imaging modalities as screening tools for breast cancer in Chinese women.

BackgroundCirculating tumor cells (CTCs) have been recognized as a sensitive biomarker for breast cancer (BC). This study aimed to comprehensively compare CTC with imaging modalities, including ultrasonography, mammography, and contrast-enhanced magnetic resonance imaging (MRI) in screening for BC in Chinese women.MethodsThree hundred forty-three participants were enrolled in this study, including 102 treatment-naive BC patients, 177 with breast benign diseases (BBD) and 64 healthy female patients. All participants underwent CTC testing and at least one of the following examinations, ultrasonography, mammography, and MRI at the Second Affiliated Hospital of Zhejiang University between December 2017 and November 2020. CTCs were quantitatively assessed using cell counting (CTC detection rate/counts) and categorically examined using a cutoff value (CTC classification). The diagnostic power of CTC tests and imaging modalities, including accuracy and capability to predict clinicopathological characteristics of BC, were evaluated and compared.ResultsCTC classification with a cutoff value of 2 showed a “good” diagnostic accuracy of 0.889 for early- to mid-stage BC comparable to breast imaging modalities using Breast Imaging-Reporting and Data System (BI-RADS). MRI demonstrated the highest sensitivity of 0.872 for BC, and CTC classification had the highest specificity of 0.938. A relatively low sensitivity was found for mammography in this cohort of patients. Successful detection of BC by CTC detection rate/counts, but not CTC classification, correlated with two important clinicopathological features, American Joint Committee on Cancer (AJCC) stage and tumor-node-metastasis (TNM) stage. The detection power of certain imaging modalities was also associated with AJCC stage (ultrasonography, p = 0.0438 and MRI, p = 0.0422) and lymph node metastasis (ultrasonography, 0.0157). There were clear correlations between CTC tests (counts or classification) and imaging BI-RADS scoring system in detecting positive BC cases (p < 0.05). Further correlation analysis suggested that CTC quantity, but not CTC classification, had the capability to predict clinicopathological traits of BC that were identified by ultrasonography.ConclusionsCTC tests have a diagnostic potency comparable to breast imaging modalities, and may be used as an alternative screening tool for BC.

Development and validation of polygenic risk scores for prediction of breast cancer and breast cancer subtypes in Chinese women

BackgroundStudies investigating breast cancer polygenic risk score (PRS) in Chinese women are scarce. The objectives of this study were to develop and validate PRSs that could be used to stratify risk for overall and subtype-specific breast cancer in Chinese women, and to evaluate the performance of a newly proposed Artificial Neural Network (ANN) based approach for PRS construction.MethodsThe PRSs were constructed using the dataset from a genome-wide association study (GWAS) and validated in an independent case-control study. Three approaches, including repeated logistic regression (RLR), logistic ridge regression (LRR) and ANN based approach, were used to build the PRSs for overall and subtype-specific breast cancer based on 24 selected single nucleotide polymorphisms (SNPs). Predictive performance and calibration of the PRSs were evaluated unadjusted and adjusted for Gail-2 model 5-year risk or classical breast cancer risk factors.ResultsThe primary PRSANN and PRSLRR both showed modest predictive ability for overall breast cancer (odds ratio per interquartile range increase of the PRS in controls [IQ-OR] 1.76 vs 1.58; area under the receiver operator characteristic curve [AUC] 0.601 vs 0.598) and remained to be predictive after adjustment. Although estrogen receptor negative (ER−) breast cancer was poorly predicted by the primary PRSs, the ER− PRSs trained solely on ER− breast cancer cases saw a substantial improvement in predictions of ER− breast cancer.ConclusionsThe 24 SNPs based PRSs can provide additional risk information to help breast cancer risk stratification in the general population of China. The newly proposed ANN approach for PRS construction has potential to replace the traditional approaches, but more studies are needed to validate and investigate its performance.

Peripheral blood EMR3 gene methylation level is correlated with breast cancer in Chinese women

To explore the association of methylation levels of C19orf57, MAP9, EMR3, NEK6 and PCOLCE2 genes in peripheral blood with breast cancer (BC) in Chinese women. We collected peripheral blood samples from 258 early-stage BC patients and 272 healthy women. Agena matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) was utilized to quantitatively measure the methylation levels of CpG sites in the genes. The association between DNA methylation and BC was analyzed using a logistic regression model adjusted for covariants. Spearman's correlation analysis was performed to analyze the association between the gene methylation levels and age. The methylation levels of the genes in the BC patients with different clinical characteristics were investigated using non-parametric tests. In stead of EMR3 gene hypermethylation as found in BC patients as found in the Caucasian population, EMR3 gene hypomethylation was found to correlate with BC in Chinese women, but this correlation was significant only in women beyond the age of 50 years (for every 10% reduction of the methylation level, EMR3_CpG_1: OR=1.40; EMR3_CpG_2: OR=2.31; EMR3_CpG_3: OR=2.76, P < 0.05). EMR3 methylation was not or was only weakly correlated with tumor stage, size, lymphatic metastasis, ER, PR, HER2, or Ki67. Our data did not show a correlation between C19orf57 methylation and BC. Peripheral blood EMR3 gene hypomethylation is associated with BC in Chinese women, especially in those at an old age and in postmenopausal women.

A longitudinal cohort study on benefit finding evolution in Chinese women breast cancer survivals

Even though the prevalence of benefit finding (BF) has been empirically shown to exist among breast cancer (BC) survivals, how does benefit finding evolve over time remains inadequately investigated. The objective of this cohort study is to examine how BF evolves over time among Chinese breast cancer survivals and determine the demographic, medical and psychosocial factors that can sustain BF increase over time. Participants were 486 women with different stages of breast cancer (stages I, II and III) followed from completion of primary treatment. Analysis were performed on the data collected during 2014–2019. During the assessment, each participant completed self-report questionnaires of characteristics and benefit finding at six time points with the interval of 6 months since BC diagnosis. The relationships between demographic, medical and psychosocial characteristics and benefit finding evolution over time were examined using mixed models. Participants reported mixed results on the evolving patterns of benefit finding: 28% reported an upward trend in BF scoring over time, 49% instead reported an downward trend, and the remaining 23% reported no obvious change. Our study has shown that some well-known covariates of benefit finding, e.g. education, income, and social support, are not associated with BF trends. In comparison, levels of spirituality and disease coping at diagnosis can more reliably predict BF evolution over time. Identifying the sustaining factors of benefit finding in the experience of breast cancer is the key to design effective psycho clinical solutions for patients’ long-term post-traumatic growth. As time goes by, breast cancer patients may experience less benefit finding. Our results strongly indicate that benefit finding can be sustained and increased by encouraging attempts at meaning-making and active disease coping during breast cancer treatment. To the best of our knowledge, this study is among the first to examine the evolution trends of benefit finding over time on breast cancer survivals and determine their psychosocial predictors in developing countries.

Coding variants in the PCNT and CEP295 genes contribute to breast cancer risk in Chinese women

BackgroundCentrioles play pivotal roles in the assembly of centrosomes, their dysfunction is associated with multiple inherited diseases or cancers. To date, few studies have focused on the associations between coding single nucleotide polymorphisms (SNPs) in the centriole duplication cycle genes and the risk of breast cancer in Chinese women. MethodsTwenty-one SNPs were selected from the coding regions of 10 critical centriole genes. The associations between the selected SNPs and breast cancer susceptibility were assessed in a case-control study of Chinese women, which included 1032 cases and 1063 controls. Potential biological functions in the influence of protein stability and the profile of expression quantitative trait loci (eQTL) of the identified SNPs were further evaluated using in silico databases. ResultsMultivariate logistic regression analyses revealed that a missense SNP rs7279204 in PCNT was significantly associated with an increased risk of breast cancer (additive model: adjusted OR=1.19, 95% CI: 1.02–1.38), while a missense SNP rs77922978 in CEP295 was significantly associated with a decreased risk of breast cancer (additive model: adjusted OR=0.74, 95% CI: 0.56–0.97). Stratification analyses suggested that rs7279204 and rs77922978 exhibited different effects among later first live birth, ER-negative and PR-negative women (P<0.05). Moreover, rs77922978 showed significant differences for ER and PR status strata (heterogeneity test P=0.028, P=0.046). In addition, bioinformatic analyses indicated that the two variants may possess potential functions of reducing the protein stability of their host genes. Further eQTL analysis showed that the rs7279204 was not only correlated with the expression of its host gene PCNT, but also correlated with the expression of its nearby genes, implying its potential roles in regulation of some cancer susceptibility genes. ConclusionsThe SNPs rs7279204 and rs77922978 within the coding region of the PCNT and CEP295 genes may contribute to the susceptibility of breast cancer in Han Chinese population.

Intronic SNP - rs9288953 Of Suppressor Molecule Btla Confers Susceptibility To B-Cell Chronic Lymphocytic Leukemia

The contribution of the immune system to the pathogenesis of B-cell chronic lymphocytic leukemia (B-CLL) have been receiving growing attention. The increase of cancer risk in immunodeficient individuals has been documented in population and experimental studies (Gurlich et al 2007; Swann et al 2007, Smyth et al 2006). A new member of co-inhibitory molecules B - and T-lymphocyte attenuator (BTLA) that inhibits lymphocyte activation could influence cancer susceptibility (Watanabe et al 2003). A high expression of BTLA was observed on malignant B cells from chronic lymphocytic leukemia/small lymphocytic leukemia (M'Hidi et al. 2009). As BTLA synthesis depends on the rate of gene transcription and/or translation, polymorphism in the corresponding gene might result in abnormal expression and function.The aim of this studywas to evaluate possible associations between selected on the basis of literature (Fu et al 2009) single nucleotide polymorphisms (SNPs) existing within exons and introns of BTLA gene: rs9288952A>G, rs1844089G>A, rs2705535C>T and 9288953C>T and susceptibility to B-CLL.Genotyping was done using allelic discrimination method with the TaqMan SNP Genotyping Assays in 300 B-CLL patients (pts.) (203 pts. from Department of Hematology, Medical University Lodz, Poland and 97 from Department of Clinical Immunology and Immunotherapy, Medical University of Lublin, Poland (138 female/162 male) and in 417 healthy individuals (168 female/243 male) originating from the same region of Poland.The significant differences in distribution of alleles and genotypes was observed for intronic SNP -rs9288953. The frequency of T allele and T alleles carriers (CT+TT genotypes) were higher in patients than in healthy controls as compare to C allele and CC genotypes (0.458 vs. 0.375, p=0.0016; OR:1.41, 95%CI - 1.13-1.75 and 0.677 vs. 0.606, p=0.0022; OR:1.67, 95%CI- 1.16-1.2.40, respectively). None of other investigated SNPs have shown different frequency of alleles or genotypes in group of patients and controls.The haplotype analysis of rs9288952A>G, rs1844089G>A, rs2705535C>T and 9288953C>T showed that the most common haplotypes rs9288952A>G[A]/rs1844089G>A[G]/rs2705535C>T[C]/ 9288953C>T[C] (named as AGCC) and rs9288952A>G[A]/rs1844089G>A[G]/rs2705535C>T[C]/ 9288953C>T[T] (named as AGCT) which were differentiate only by variants of 9288953C>T SNP were completely contrary associated with disease susceptibility. Haplotype AGCC is associated with decreased risk of B-CLL (OR: 0.72, 95%CI-0.59-0.90 p with Bonferroni correction=0.01), while AGCT with increased risk of disease (OR: 1.42, 95%CI-1.14-1.76 p with Bonferroni correction=0.005)Our data indicated for the first time the possible role of intronic polymorphism 9288953C>T in gene encoding suppressor molecule BTLA in susceptibility to B-CLL. ReferencesFu Z, Li D, Jiang W, Wang L, Zhang J, Xu F, Pang D, Li D. Association of BTLA gene polymorphisms with the risk of malignant breast cancer in Chinese women of Heilongjiang Province. Breast Cancer Res Treat. 2010 Feb;120(1):195-202.Grulich AE, van Leeuwen MT, Falster MO, Vajdic CM. Incidence of cancers in people with HIV/AIDS compared with immunosuppressed transplant recipients: a meta-analysis. Lancet. 2007 Jul 7;370(9581):59-67.M'Hidi H, Thibult ML, Chetaille B, Rey F, Bouadallah R, Nicollas R, Olive D, Xerri L. High expression of the inhibitory receptor BTLA in T-follicular helper cells and in B-cell small lymphocytic lymphoma/chronic lymphocytic leukemia.Am J Clin Pathol. 2009 Oct;132(4):589-96.Smyth MJ, Dunn GP, Schreiber RD. Cancer immunosurveillance and immunoediting: the roles of immunity in suppressing tumor development and shaping tumor immunogenicity. Adv Immunol. 2006;90:1-50.Swann JB, Smyth MJ. Immune surveillance of tumors. J Clin Invest. 2007 May;117(5):1137-46.Watanabe N, Gavrieli M, Sedy JR, Yang J, Fallarino F, Loftin SK, Hurchla MA, Zimmerman N, Sim J, Zang X, Murphy TL, Russell JH, Allison JP, Murphy KM. BTLA is a lymphocyte inhibitory receptor with similarities to CTLA-4 and PD-1.Nat Immunol. 2003 Jul;4(7):670-9. Disclosures:No relevant conflicts of interest to declare.

Prevalence and characteristics of mouse mammary tumor virus-like virus associated breast cancer in China

BackgroundDespite extensive molecular epidemiological studies, the prevalence and characteristics of Mouse Mammary Tumor Virus-Like Virus (MMTV-LV) in Chinese women breast cancer are still unclear. Besides, the prevalence of MMTV-LV in women breast cancer tissue varies in different countries and its dependent factors remain inconclusive.MethodsIn the first part of the study, a case-control study was performed. 119 breast cancer samples (84 from Northern China and 35 from Southern China) and 50 breast fibroadenoma specimens were collected from Chinese women patients. MMTV-like env sequence and the homology to MMTV env gene were analysed by semi-nested polymerase chain reaction (PCR). We also explored the association of MMTV-LV prevalence with sample sources (Southern and Northern China) and patients’ clinicopathological characteristics. To investigate the dependent factors of the prevalence of MMTV-LV in breast cancer worldwide, a meta-analysis was conducted in the second part of the study.ResultsWe found that the prevalence of MMTV-LV was much higher in breast cancer tissues (17.65%) than that in breast fibroadenoma specimens (4.00%) (P < 0.05). MMTV-LV prevalence in Chinese women breast cancer tissues was significantly different between Southern China (5.71%) and Northern China (22.62%) (P < 0.05). The prevalence of MMTV-LV also associates significantly with expression of HER2, but shows no significant correlation with other parameters. In the meta-analysis, we found that MMTV-LV prevalence in breast cancer tissue was dependent on the distribution of M. domesticus mouse (M. d), M. musculus mouse (M.m) and M.castaneus mouse (M.c) worldwide (P < 0.05).ConclusionThe distribution of house mice may be a crucial environmental factor that explains the geographic differences in human breast cancer incidence. Our findings may provide a potential avenue of prevention, diagnosis and treatment for breast cancer.

Application of artificial intelligence based on deep learning in breast cancer screening and imaging diagnosis

In recent years, with the change of lifestyle in Europe and America, the incidence of breast cancer in Chinese women is increasing. In order to find the model of breast cancer image screening and diagnosis with higher accuracy and better classification performance, this paper mainly constructs the breast cancer CT image detection model and the breast cancer screening model based on the convolution and deconvolution neural network (CDNN) through the convolution neural network (CNN). In this paper, the fuzzy C-means clustering algorithm (FCM) is used to improve and optimize the image of breast cancer, and the experimental results are analyzed. The optimized kernel fuzzy C-means clustering algorithm was tested on a common dataset to segment the region of interest more accurately. Our experiments show that the new deep learning model of this paper improves the automatic classification performance of breast cancer. In this paper, the research results of deep learning are applied to the medical field, and a new method based on CNN model for breast cancer screening and diagnosis is proposed, which provides a new idea for improving the artificial intelligence assisted medical diagnosis method.

P050 - Adiposity and risk of breast cancer in Chinese women

P050 - Adiposity and risk of breast cancer in Chinese women