BACKGROUND:Breast calcifications are frequent mammographic findings and serve as critical indicators for the early detection of breast cancer. Breast calcifications are formed by a mineralization process considered passive deposits resulting from tissue necrosis, but accumulating evidence suggests that calcifications may instead arise from active stromal remodeling within the tumor microenvironment. Among the diverse stromal components, mesenchymal stem cells are particularly implicated in mediating mineralization processes. Adipose-derived mesenchymal stem cells (ADSCs), abundant in breast tissue and possessing strong osteogenic potential, could therefore play a key role in mineralization process. However, their contribution of ADSCs to malignant calcification formation remains poorly understood. METHODS:RNA sequencing was performed on malignant and benign calcified breast tissues to identify differentially expressed genes. Candidate genes were validated using public datasets, immunohistochemistry and survival analysis. ADSCs were isolated from patient breast tissue, phenotypically characterized and genetically modified to overexpress SQLE or HGD genes. Osteogenic differentiation was assessed by alkaline phosphatase activity, Alizarin Red S staining, qPCR and Western blot. In vivo effects were evaluated using a breast cancer xenograft model. Transcriptomic profiling, Seahorse mitochondrial stress analysis, JC-1 staining, reactive oxygen species (ROS) quantification, calcium imaging and transmission electron microscopy were used to explore the underlying mechanisms. RESULTS:Transcriptomic screening identified SQLE as a top upregulated gene in malignant calcifications, correlating with poor patient survival. SQLE was highly expressed in stromal cells of malignant lesions. Functional assays showed that the overexpressed SQLE markedly enhanced ADSC osteogenic differentiation and matrix mineralization, with a stronger effect than HGD. In vivo, SQLE-overexpressing ADSCs promoted ectopic calcification within tumors. Mechanistically, the overexpressed SQLE altered the ADSC transcriptome, enriched cancer- and calcium-related pathways, impaired mitochondrial oxidative phosphorylation, reduced mitochondrial membrane potential and ROS levels, and induced mitochondrial calcium accumulation with mineral deposition. The upregulation of PMCA2 and MCU mediated by overexpressed SQLE occurred prior to differentiation, followed by sustained mitochondrial calcium accumulation. CONCLUSIONS:This study identifies SQLE as a novel driver of stromal mineralization and malignant breast calcification via mitochondrial dysfunction and calcium dysregulation. These findings challenge the passive necrosis model of calcification, positioning SQLE as both a biomarker for malignant calcifications and a potential therapeutic target for microenvironment-focused breast cancer interventions.

BackgroundLong-non-coding RNA PVT1 (lncRNA PVT1) can be used as an oncogenic regulatory non-coding RNA (ncRNA) for many cancers. However, its function and mechanism in breast cancer (BRCA) are still not clearly elucidated.ObjectiveWe attempt to explain the mechanism of PVT1's role in breast cancer from different perspectives.MethodsWe analyzed the expression of PVT1 and its correlation with the breast cancer related clinical data in the The Cancer Genome Atlas (TCGA) database. We used PVT1 overexpression and knockdown lentivirus to infect breast cancer MDA-MB-231 cell line for cell function verification, in vitro using CCK-8 to measure proliferation, flow cytometry to measure apoptosis, transwell test to measure invasion and migration ability, detecting cell extracellular acidification rate (ECAR) to assess glycolysis metabolism and explore the biological functions of PVT1 in breast cancer cells. Transcriptome sequencing was used to analyze the changes of related genes in cells after overexpression of PVT1. In vivo we used a xenograft model to study the effect of PVT1 on breast cancer.ResultsPVT1 was up-regulated in breast cancer tissues and was positively correlated with the clinical stage of breast cancer patients. Overexpression of PVT1 in vitro promoted cell proliferation, migration and invasion, and promoted tumor growth in vivo. Knockdown of PVT1 led to the opposite biological consequence. Further bioinformatics analysis showed that PVT1 changes the glycolysis metabolism of tumors through regulation of glycolysis-related genes. In addition, the expression of miR-145-5p is negatively correlated with PVT1. We consider the possibility of PVT1 promoting cell proliferation and metastasis by regulating the aerobic glucose metabolism in breast cancer cells through sponging the miR-145-5p.ConclusionOur results reveal a potential pathway for competing endogenous RNA to regulate breast cancer glucose metabolism. PVT1 regulates glycolysis related genes expression by competitively binding to endogenous miR-145-5p in breast cancer cells to change the metabolic phenotype. This may Provide new ideas for precise molecular therapy targets for breast cancer.

Identifying reliable biomarkers to determine whether mild cognitive impairment (MCI) progresses to Alzheimer's disease (AD) has become a major focus in neurology. As a functional imaging technique, positron-emission computed tomography (PET) has been extensively employed in diagnosing and evaluating neurodegenerative diseases. However, changes in brain metabolic patterns, based on 18F-Fluoro-2-deoxyglucose (18F-FDG)-PET, are not specific to AD and cannot accurately identify MCI patients with a high risk of progression to AD. Radiomics is an approach to medical image analysis that employs quantitative methods to gain additional information from existing data, with the aim of aiding clinicians through advanced mathematical analysis. Radiomics was initially used mainly in oncology, however, its universality has allowed it to be employed in neurology as well.

BACKGROUND:In patients with systemic lupus erythematosus (SLE), myocardial involvement is the third leading course of death after lupus nephropathy (LN) and infections. Previous autopsy studies have demonstrated a high incidence of cardiovascular abnormalities in the myocardium. However, the patients with typical symptoms are far much fewer than expected from post-mortem examinations.OBJECTIVES:The current study aimed to evaluate the technetium-99m-sestamibi (99mTc-MIBI) gated myocardial perfusion imaging (GMPI) characteristics of lupus patients without cardiovascular symptoms, and the relationships between GMPI characteristics and biochemical markers of myocardial injury, and to explore the role of GMPI in assessing myocardial involvement.METHODS:Thirty patients were studied with rest myocardial perfusion imaging, and summed rest score (SRS), summed motion score (SMS), and summed thickening score (STS) were calculated automatically. Biomarkers, including N-terminal prohormone of brain natriuretic peptide (NT-proBNP) and creatine-kinase-MB (CK-MB), were detected simultaneously. GMPI parameters, LV functions and biomarkers were compared between two NT-proBNP groups. The relationships between these parameters were studied by correlation analysis.RESULTS:SMS, STS, and glomerular filtration rate (eGFR) were the main influencing factors of NTproBNP level (p = 0.001, <0.001, 0.042, respectively). Thirteen patients with an evaluated concentration of NT-proBNP had the lower left ventricular ejection fraction (LVEF), peak filling rate (PFR), eGFR and higher levels of CK-MB (in all comparisons, p < 0.05), and SRS was the only influencing factor of NT-proBNP (p = 0.007). Within thirteen patients with SRS≥2, there was a significant correlation between SRS and NT-proBNP (p < 0.001).CONCLUSION:99mTc-MIBI GMPI could evaluate the left ventricular function and prompt the cardiomyocyte function at the cellular level. SMS and STS were the main influencers for plasma NT-proBNP, and SRS was the independent factor for elevated NT-proBNP. This radionuclide imaging method could provide additional diagnostic information on myocardial involvement in patients with SLE.

AbstractBackground Several traditional observational studies suggested a strong association between frailty with coronavirus disease 2019 (COVID-19). However, whether the observed association reflects causality remained unclear. We employed a bidirectional Mendelian randomization (MR) study to investigate the causal relationship of frailty, measured by the Frailty Index and Fried Frailty Score, with COVID-19. Methods We extracted summary genome-wide association statistics for the Frailty Index (N = 164,610), Fried Frailty Score (N = 386,565), COVID-19 (Ncase = 159,840, Ncontrol = 2,782,977), hospitalized COVID-19 (Ncase = 44,986, Ncontrol = 2,356,386) and severe COVID-19 (Ncase = 18,152, Ncontrol = 1,145,546). Independent single nucleotide polymorphisms at genome-wide significance for each phenotype were taken as instruments. The random-effects inverse‐variance weighted method was applied as the primary method, followed by various sensitivity and validation analyses. Results No causal effect of Frailty Index between COVID-19 was observed. Genetically predicted Fried Frailty Score was significantly associated with increased risk of COVID-19 hospitalization (odds ratio [OR] 2.06, 95% confidence interval [CI] 1.45–2.91, P < 0.0001), and suggestively associated with higher risk of COVID-19 susceptibility (OR = 1.19, 95% CI 1.01–1.39; P = 0.035) and COVID-19 severity (OR = 2.10, 95% CI 1.10–4.01; P = 0.025). Sensitivity and validation analyses also received broadly concordant results. There is no insignificant association for reverse causation. Conclusion Our study demonstrated that Fried Frailty Score could increase the risk of COVID-19. Future development should focus on long-term mutual influence between frailty and COVID-19 to alleviate the complications of diseases.

Abstract Objective The aim of this study was to analyze the relationship of serum gastrin-17 (G-17) and oral mucositis in head and neck carcinoma (HNC) patients receiving radiotherapy. Methods Serum G-17 were detected in patients before and after radiotherapy. Patients were divided into high G-17 group (baseline serum G-17 ≥ 5pmol/L) and low G-17 group (baseline serum G-17 < 5pmol/L). The severity of oral mucositis was analyzed between the two groups. Other complications such as dysphagia, salivary gland, mandible, thyroid function, larynx, pain, and weight loss were also investigated. Results Forty-two patients were analyzed in this study. The level of serum G-17 had a significant decrease after radiotherapy (7.29 ± 5.70pmol/L versus 4.93 ± 4.46pmol/L, P = 0.038). In low serum G-17 group, the incidences of grade 0, 1–2 and 3–4 of oral mucositis were 0%, 30.4%, and 69.6%, respectively. In high serum G-17 group, the incidences of grade 0, 1–2 and 3–4 of oral mucositis were 0%, 63.2%, and 36.8%, respectively. Pearson correlation analysis showed that serum G-17 was negatively correlated with oral mucositis (r=-0.595, P < 0.01). Weight loss of low G-17 group was more serious than that of high G-17 group. Conclusion Serum G-17 has a close relationship with oral mucositis. Baseline serum G-17 may be a potential predictor for the severity of oral mucositis in HNC patients receiving radiotherapy.

Triple-negative breast cancer (TNBC) is often treated with anthracyclines (e.g., epirubicin or doxorubicin), but very little is known about anthracycline resistance, especially epirubicin resistance in TNBC. To identify novel long noncoding RNAs (lncRNAs) involved in epirubicin resistance in TNBC, we established a new TNBC MDA-MB-231 cell line that was resistant to epirubicin (Epi-R). A total of 12 differentially expressed lncRNAs were identified using RNA sequencing analysis of Epi-R cells. Among these lncRNAs, we found a novel intronic lncRNA, lnc005620, was highly expressed in Epi-R cells and human TNBC tissues. Further gain- and loss-of-function studies demonstrated that lnc005620 played an oncogenic role and partially abrogated the effects of epirubicin on TNBC cells. Using iTRAQ proteomics analysis, we found that three members of the integrin family, integrin β4, integrin β1 and integrin α6, were all upregulated in Epi-R MDA-MB-231 cells. Integrin β1, encoded by the ITGB1 gene, was validated to be a downstream target of lnc005620 in Epi-R MDA-MB-231 cells. Our study demonstrates that novel lnc005620 promotes TNBC progression and chemoresistance to epirubicin via integrin β1 both in vitro and in vivo and provides a promising therapeutic target for TNBC patients in terms of enhancing the benefits of epirubicin treatment.

Objective:To explore the significance of the abundance of enterococcus faecalis in the prediction of recurrence in patients with colorectal cancer.Methods:All The 103 fecal samples were collected from patients with recurrent colorectal cancer and non-recurrent colorectal cancer at the deparment of general surgery in the fourth affiliated hospital of Harbin Medical University. 16S sequencing technology was used to search for different intestinal flora. Statistical analysis was used to explore the relationship between different flora and clinical pathological indicators of patients and relapse-free survival.Results:Enterococcus faecalis in patients with recurrent organization is higher abundance in stool samples, the patients who have higher abundance in stool samples has more pathological indicators of poor prognosis, meanwhile we also find that high abundance of dung enterococcus in patients have shorter total survival time and shorter relapse-free survival.Conclusion:The abundance of Enterococcus faecalis in fecal samples may be a new marker to judge the prognosis of patients with colorectal cancer in the future.

Triple negative breast cancer (TNBC) is an aggressive subtype of breast cancer that currently lacks effective biomarkers and therapeutic targets required to investigate the diagnosis and treatment of TNBC. Here we performed a comprehensive differential analysis of 165 TNBC samples by integrating RNA-seq data of breast tumor tissues and adjacent normal tissues from both our cohort and The Cancer Genome Atlas (TCGA). Pathway enrichment analysis was conducted to evaluate the biological function of TNBC-specific expressed genes. Further multivariate Cox proportional hazard regression was performed to evaluate the effect of these genes on TNBC prognosis. In this report, we identified a total of 148 TNBC-specific expressed genes that were primarily enriched in mammary gland morphogenesis and hormone levels related pathways, suggesting that mammary gland morphogenesis might play a unique role in TNBC patients differing from other breast cancer types. Further survival analysis revealed that nine genes (FSIP1, ADCY5, FSD1, HMSD, CMTM5, AFF3, CYP2A7, ATP1A2, and C11orf86) were significantly associated with the prognosis of TNBC patients, while three of them (ADCY5, CYP2A7, and ATP1A2) were involved in the hormone-related pathways. These findings indicated the vital role of the hormone-related genes in TNBC tumorigenesis and may provide some independent prognostic markers as well as novel therapeutic targets for TNBC.

Radiotherapy is a frequent mode of cancer treatment, although the development of radioresistance limits its effectiveness. Extensive investigations indicate the diversity of the mechanisms underlying radioresistance. Here, we aimed to explore the effects of extracellular signal-regulated kinase 5 (ERK5) on lung cancer radioresistance and the associated mechanisms. Our data showed that ERK5 is activated during solid lung cancer development, and ectopic expression of ERK5 promoted cell proliferation and G2/M cell cycle transition. In addition, we found that ERK5 is a potential regulator of radiosensitivity in lung cancer cells. Mechanistic investigations revealed that ERK5 could trigger IR-induced activation of Chk1, which has been implicated in DNA repair and cell cycle arrest in response to DNA double-strand breaks (DSBs). Subsequently, ERK5 knockdown or pharmacological inhibition selectively inhibited colony formation of lung cancer cells and enhanced IR-induced G2/M arrest and apoptosis. In vivo, ERK5 knockdown strongly radiosensitized A549 and LLC tumor xenografts to inhibition, with a higher apoptotic response and reduced tumor neovascularization. Taken together, our data indicate that ERK5 is a novel potential target for the treatment of lung cancer, and its expression might be used as a biomarker to predict radiosensitivity in NSCLC patients.

Long non‐coding RNAs (lncRNAs) participate in the development of breast cancer. Genetic variants in lncRNAs may be involved in their abnormal expressions and associated with cancer risk. In the present study, we performed RNA sequencing on five paired breast cancer tumor and adjacent non‐cancerous tissues to obtain differentially expressed lncRNAs. We systematically selected potential regulatory variants of these lncRNAs and investigated the associations between these variants and breast cancer susceptibility in 1486 breast cancer cases and 1519 cancer‐free controls in a Chinese population. Eleven lncRNAs were significantly differentially expressed between breast cancer tumor and normal tissues (false discovery rate (FDR) ≤0.05 and fold‐change ≥2), including two known lncRNAs HOTAIR and UCA1. We subsequently genotyped 20 variants located on these lncRNAs and identified two variants (rs11471161 in AC104135.3 and rs3751232 in RP11‐1060J15.4) associated with breast cancer risk. Logistic regression analysis indicated that the variant allele of rs11471161 was significantly associated with a decreased breast cancer risk (additive model: OR = 0.84, 95%CI = 0.74‐0.94, P = 0.004), while the variant allele of rs3751232 showed an increased risk of breast cancer (additive model: OR = 1.20, 95%CI = 1.02‐1.40, P = 0.027). Further co‐expression analysis indicated that AC104135.3 associated with ERBB2, which promotes the development and progression of breast cancer through overexpression. Together, these results suggest that genetic variants rs11471161 and rs3751232 in AC104135.3, and RP11‐1060J15.4, respectively, may influence the susceptibility to breast cancer in the Chinese population. Further functional evaluations and larger studies are warranted to validate these findings.

Heterogeneity is the major obstacle to breast cancer target therapy. Classification of breast cancer with significant biological process may reduce the influence of heterogeneity of intrinsic tumor. We used survival analysis to filter 95 gene sets and classify 638 breast cancer samples into two subtypes based on those gene sets associated with prognosis. Clinical outcome of two subtypes were evaluated with disease-free survival, distant metastasis-free survival, and overall survival levels in three databases and ER+, PR+ HER2+, and TNBC groups. We established a novel classification with 95 prognostic gene sets. In the training and validation cohorts, the subtype 1 was characterized by significant gene sets associated with regulation of metabolic process and enzyme activity and predicted obviously improved clinical outcome than subtype 2, which was enriched by tumor cell division, mitosis, and cell cycle-related gene sets (P < 0.05). When evaluated prognostic impact of subtypes in ER+, PR+ HER2+, and TNBC groups, we found that patients in subtype 1 showed better prognosis in ER+ and PR+ groups (P < 0.05) but had no difference from prognosis of subtype 2 in HER2+ and TNBC groups. These findings may have implications in understanding of breast cancer and filtering effective therapeutic strategies for targeted therapy.

Long noncoding RNAs (lncRNAs) have been gradually confirmed to be tumor-associated biological molecules and became interesting new diagnostic targets of cancer. However, the clinical significances of most cancer-related lncRNAs are largely unknown. Here, we evaluated, for the first time, the feasibility and clinical significances of circulating serum lncRNA RP11-445H22.4 as biomarker for the detection of breast cancer (BC). In this study, the relative concentrations of breast cancer-associated lncRNA RP11-445H22.4 were investigated in a total of 136 serum samples by real-time quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). The correlations between the levels of serum lncRNA RP11-445H22.4 in breast cancer patients and the clinicopathological factors of these patients were further analyzed. Receiver operating characteristic (ROC) curve was constructed to evaluate the diagnostic values. In breast cancer patients, the expression level of lncRNA RP11-445H22.4 is significantly increased ( p < 0.001). The sensitivity and specificity of RP11-445H22.4 for BC were 92 and 74 %, respectively. Its expression levels were correlated with estrogen receptor (ER), progesterone receptor (PR), and menopausal status of the breast cancer patients ( p < 0.05). For the detection of breast cancer, the use of RP11-445H22.4 showed a remarkable improvement compared with the clinical serum carcinoembryonic antigen. In conclusions, lncRNA RP11-445H22.4 may be a new potential biomarker of breast cancer.

Background: P-glycoprotein (P-gp) can efflux drugs from cancer cells, and its overexpression is commonly associated with multi-drug resistance (MDR). Thus, the accurate quantification of P-gp would help predict the response to chemotherapy and for prognosis of breast cancer patients.Methods: An advanced liquid chromatography-tandem mass spectrometry (LC/MS/MS)-based targeted proteomics assay was developed and validated for monitoring P-gp levels in breast tissue.Results: Tryptic peptide 368IIDNKPSIDSYSK380 was selected as a surrogate analyte for quantification, and immuno-depleted tissue extract was used as a surrogate matrix. Matched pairs of breast tissue samples from 60 patients who were suspected to have drug resistance were subject to analysis. The levels of P-gp were quantified. Using data from normal tissue, we suggested a P-gp reference interval. The experimental values of tumor tissue samples were compared with those obtained from Western blotting and immunohistochemistry (IHC). The result indicated that the targeted proteomics approach was comparable to IHC but provided a lower limit of quantification (LOQ) and could afford more reliable results at low concentrations than the other two methods.Conclusions: LC/MS/MS-based targeted proteomics may allow the quantification of P-gp in breast tissue in a more accurate manner. (C) 2014 Elsevier B.V. All rights reserved.

BACKGROUND/AIMS:Breast cancer chemoresistance is a major obstacle to the successful treatment of patients. miRNAs perform critical roles in biological processes, including tumorigenesis and chemoresistance. However, little clinical data are available regarding the relationship between miRNA expression patterns and breast cancer chemoresistance. METHODS:We created a doxorubicin-resistant MCF-7 (MCF-/Adr) cell line using a pulse-selection method; then verified the resistance of the MCF-7/Adr cell line to doxorubicin by using the methyl thiazolyl tetrazolium (MTT) assay, terminal deoxyribonucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL) staining, and Intracellular doxorubicin accumulation assay. Then, we performed qRT-PCR to detect the expression patterns of 14 selected miRNAs (which are related to breast cancer resistance) in both cell lines. Subsequently, we performed a bioinformatics analysis, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, to determine the putative functions of 13 differentially expressed miRNA-targeted genes. Finally, we tested the expression levels of these 13 miRNAs in 10 chemotherapy non-responder breast cancer tissues and 29 responder tissues. All statistical analyses were performed by a two-tailed Student's t-test, and a P value less than 0.05 was considered statistically significant. RESULTS:The results of the MTT assay showed that the MCF-7/Adr cell line was significantly more resistant to doxorubicin compared to the MCF-7 cells The results of the TUNEL assay indicated that doxorubicin induced an increase in the number apoptotic cells in the MCF-7 group. Additionally, the accumulation of doxorubicin was higher in MCF-7 cells compared to MCF-7/Adr cells, which was consistent with the MTT and TUNEL results. The qRT-PCR results demonstrated that compared to the parental MCF-7 cell line, miR-200a, miR-141, miR-200c, miR-31, miR-429, and miR-196b were over-expressed, and let-7e, miR-576-3p, miR-125b-1, miR-370, miR-145, miR-765, and miR-760 were significantly down-regulated in MCF-7/Adr cells. The GO analysis results revealed that the predicted target genes of these 14 miRNAs primarily regulated protein binding, zinc ion binding, DNA binding, and transcription factor activity. The KEGG data demonstrated that these target genes are mainly involved in the MAPK signaling pathway, regulation of the actin cytoskeleton, cytokine-cytokine receptor interaction, and other signaling pathways. Compared to the breast cancer tissues from chemotherapy responders, 10 miRNAs were identified to be dysregulated in the chemoresistant breast cancer tissues. Three of these miRNAs were up-regulated (miR-141, miR-200c, and miR-31), and 7 were down-regulated (let-7e, miR-576-3p, miR-125b-1, miR-370, miR-145, miR-765, and miR-760). CONCLUSION:In this study, we identified 10 dysregulated miRNAs in both breast cancer cells and chemoresistant tissues, which might be biomarkers for the prognosis of breast cancer chemoresistance. Our study contributes to a comprehensive understanding of prognostic biomarkers during clinical treatment, and we hypothesize that the miRNA signatures of drug-resistant carcinoma tissues could be useful for developing new strategies for targeted therapies in patients with chemoresistant breast cancer.

目的:研究Tat-p53融合蛋白在乳腺癌细胞的表达、纯化及其转导活性,探讨蛋白转导方法在乳腺癌治疗中应用的可能性。方法:利用RT-PCR方法从A549细胞系中分离野生型p53基因,将该基因克隆入pTAT-HA原核表达载体,在大肠杆菌BL21（DE3）LysS内诱导表达并进行纯化。将Tat-p53融合蛋白加入MCF-7人乳腺癌细胞培养上清,检测Tat-p53融合蛋白导入MCF-7人乳腺癌细胞的情况。结果:成功地构建了含有野生型p53基因的原核表达载体,表达纯化了Tat-p53融合蛋白,证实Tat-p53可以高效转入MCF-7人乳腺癌细胞内。结论:TatPTD可以发挥高效的蛋白转导特性将p53导入人乳腺癌细胞,p53在细胞核内可以发挥生物学活性,抑制肿瘤细胞生长并诱导其发生凋亡。

PURPOSE:Mammography has been confirmed as the only effective mode to improve the prognosis of patients with breast cancer in Western developed countries, but might not be a good choice in other areas of the world. One of the major challenges in China is to determine an optimal imaging modality for breast cancer screening. This study was designed to clarify the sensitivity of ultrasonography compared with that of mammography in rural China. METHODS:We retrospectively studied the sensitivity of mammography and ultrasonography based on 306 breast cancer patients detected by the program of "screening for cervical cancer and breast cancer" performed in Chinese rural areas between January 2009 and December 2011, and analyzed the effects of age, breast density and volume on the sensitivity. RESULTS:Stratified analysis showed that the sensitivity of breast ultrasonography was significantly higher than that of mammography in premenopausal patients (81.4% vs. 61.1%, p=0.02), in women ≤ 55 years of age (82.2% vs. 63.4%, p<0.01), in the high breast density group (American College of Radiology [ACR] levels 3-4) (85.9% vs. 60.6%, p<0.01) and in the small breast volume group (≤ 400 ml) (87.1% vs. 66.7%, p<0.01). Age had a significant effect on sensitivity of mammography (breast density and volume-adjusted odds ratio, 6.39; 95% confidence interval, 2.8-14.4 in age group > 55 compared to age group ≤ 45), but not that of ultrasonography. Neither breast density nor volume had significant effect on sensitivity of mammography or ultrasonography. CONCLUSIONS:Ultrasonography is more sensitive than mammography in detecting breast cancer in women under 55 year-old Chinese, especially in those with high-density and relatively small breasts.