A prognostic nomogram for predicting breast cancer survival based on mammography and AJCC staging.

Rationale and objectives: To develop a prognostic nomogram using mammography data and AJCC staging to predict breast cancer survival. Materials and methods: A prognostic nomogram was created using data from 1000 women diagnosed with breast cancer at a medical cancer center in Taiwan between 2011 and 2015. The variables included age at diagnosis (≤60 or > 60 years), mammography purpose (screening or diagnostic), mammography modality (digital mammogram or digital breast tomosynthesis), and the 7th American Joint Committee on Cancer (AJCC) stage. The outcome predicted was breast cancer-related mortality. The nomogram utilized Kaplan-Meier analysis for all subsets and Cox proportional hazards regression analysis for prediction. The nomogram's accuracy was internally validated using the concordance index and receiver operating characteristic (ROC) curve analysis, focusing on 3-year and 5-year survival predictions. Results: Participants' mean age at breast cancer diagnosis was 54 years (SD = 11.2 years). The 1-year, 3-year, and 5-year overall survival (OS) rates were found to be 99.7%, 95.3%, and 91.4%, respectively. The bootstrap-corrected concordance indices indicated the following: nomogram, 0.807 and AJCC, 0.759. A significant difference was observed between the nomogram's area under the curve (AUC) and the AJCC stage in predicting the probability of 5-year survival (p = 0.005). A nomogram, constructed based on mammography and AJCC, demonstrated excellent calibration through internal validation using bootstrapping. Conclusion: The utilization of a nomogram that incorporates mammography data and the AJCC registry data has been demonstrated to be a reliable predictor of breast cancer survival.

Contrast-enhanced ultrasound-guided biopsy of suspicious breast lesions on contrast-enhanced mammography and contrast-enhanced MRI: a case series.

PURPOSE: To assess the effectiveness of contrast-enhanced ultrasound (CEUS) in guiding biopsies of breast lesions that were detected on contrast-enhanced mammography (CEM) or contrast-enhanced breast MRI (CE-MRI) but were not clearly visible on B-mode ultrasound (B-US). METHODS: In this study, 23 lesions in 16 patients were selected for CEUS-guided biopsy due to poor visualization on B-US despite being detected on CEM (n = 20) or CE-MRI (n = 3). B-US, color Doppler ultrasound (CDUS), and CEUS were used to visualize the suspicious lesions, followed by a CEUS-guided core needle biopsy using Sonazoid as the contrast agent. The accuracy of the biopsy was assessed based on pathology-radiology concordance and 12-month imaging follow-up. The conspicuity scores for lesion visualization were evaluated using a 5-point conspicuity scale agreed upon by two breast radiologists. RESULTS: The enhancing lesions detected on CEM/CE-MRI had an average size of 1.6 ± 1.3 cm and appeared as mass-enhancing (61%) or non-mass-enhancing (39%). The lesions had mean conspicuity scores of 2.30 on B-US, 2.78 on CDUS, and 4.61 on CEUS, with 96% of the lesions showing contrast enhancement on CEUS. CEUS-guided biopsy showed increased visibility in 96% and 91% of the lesions compared to B-US and CDUS, respectively. The overall accuracy of CEUS-guided biopsy was 100% based on concordance with histology and 12-month follow-up. CONCLUSIONS: CEUS enhances the visibility of suspicious CEM/CE-MRI lesions that are poorly visible on B-US during biopsy procedures.

Impact of contrast-enhanced mammography in surgical management of breast cancers for women with dense breasts: a dual-center, multi-disciplinary study in Asia.

OBJECTIVE: To evaluate the impact of pre-operative contrast-enhanced mammography (CEM) in breast cancer patients with dense breasts. METHODS: We conducted a retrospective review of 232 histologically proven breast cancers in 200 women (mean age: 53.4 years ± 10.2) who underwent pre-surgical CEM imaging across two Asian institutions (Singapore and Taiwan). Majority (95.5%) of patients had dense breast tissue (BI-RADS category C or D). Surgical decision was recorded in a simulated blinded multi-disciplinary team setting on two separate scenarios: (i) pre-CEM setting with standard imaging, and clinical and histopathological results; and (ii) post-CEM setting with new imaging and corresponding histological findings from CEM. Alterations in surgical plan (if any) because of CEM imaging were recorded. Predictors CEM of patients who benefitted from surgical plan alterations were evaluated using logistic regression. RESULTS: CEM resulted in altered surgical plans in 36 (18%) of 200 patients in this study. CEM discovered clinically significant larger tumor size or extent in 24 (12%) patients and additional tumors in 12 (6%) patients. CEM also detected additional benign/false-positive lesions in 13 (6.5%) of the 200 patients. Significant predictors of patients who benefitted from surgical alterations found on multivariate analysis were pre-CEM surgical decision for upfront breast conservation (OR, 7.7; 95% CI, 1.9-32.1; p = 0.005), architectural distortion on mammograms (OR, 7.6; 95% CI, 1.3-42.9; p = .022), and tumor size of ≥ 1.5 cm (OR, 1.5; 95% CI, 1.0-2.2; p = .034). CONCLUSION: CEM is an effective imaging technique for pre-surgical planning for Asian breast cancer patients with dense breasts. KEY POINTS: • CEM significantly altered surgical plans in 18% (nearly 1 in 5) of this Asian study cohort with dense breasts. • Significant patient and imaging predictors for surgical plan alteration include (i) patients considered for upfront breast-conserving surgery; (ii) architectural distortion lesions; and (iii) tumor size of ≥ 1.5 cm. • Additional false-positive/benign lesions detected through CEM were uncommon, affecting only 6.5% of the study cohort.

Contrast-enhanced ultrasound features of breast capillary hemangioma: a case report and review of literature.

Breast capillary hemangioma is a rare benign vascular tumor. A 59-year-old asymptomatic woman underwent screening mammography and breast ultrasound. B-mode ultrasound revealed a lobulated, hypoechoic mass. Color Doppler ultrasound showed no intratumoral blood flow. Contrast-enhanced ultrasound (CEUS) revealed internal fast homogeneous contrast enhancement of the mass and persistent enhancement after 4 min. A 14-gauge core needle biopsy was then performed. The radiologic and pathologic appearances were concordant with breast capillary hemangioma. The ultrasonic manifestations of breast hemangioma may vary, and differentiation from other inflammatory diseases and malignancies is challenging. CEUS may help in observing the vascular characteristics of breast capillary hemangioma.

Delayed Breast Cancer Detection in an Asian Country (Taiwan) with Low COVID-19 Incidence.

PURPOSE: To assess whether the COVID-19 pandemic delayed breast cancer diagnosis in Taiwan, an Asian country with a low COVID-19 incidence. METHODS: The monthly volume of breast biopsies and breast cancers during the COVID-19 pandemic (during January 21 and July 31, 2020) was compared to the same period in 2019 (pre-COVID-19). RESULTS: Taiwan recorded a lower COVID-19 incidence rate (20.2 cases per million population) than other Asian countries. The screen-detected lesions accounted for 55% and 36% of 2019 and 2020 total biopsied lesions, respectively. Total breast biopsy, mammography-guided, and ultrasound-guided biopsies decreased by 17%, 23%, and 14%, respectively, from pre-COVID-19 to COVID-19. Monthly differences were significant in total biopsy (p=0.03), mammography-guided biopsy (p=0.04), and a benign pathology result after breast biopsy (p<0.01). Nearly 46% decline was noted in the biopsy results of non-invasive breast cancer in 2020. The number of total breast cancers and early breast cancers (stages 0 and 1) decreased by 10% and 38%, respectively, during pandemic. Individuals with early breast cancer accounted for 71% and 49% of the total diagnosed breast cancer in the pre-COVID-19 and COVID-19 periods, respectively (p<0.001). CONCLUSION: The pandemic significantly delayed early breast cancer detection in Taiwan despite low COVID-19 incidence. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT04750018.

Architecture distortion score (ADS) in malignancy risk stratification of architecture distortion on contrast-enhanced digital mammography.

OBJECTIVE: To develop a risk predictor model in evaluation of tomosynthesis-detected architectural distortion (AD) based on characteristics of contrast-enhanced digital mammography (CEDM). METHODS: Ninety-four AD lesions on CEDM in combination with tomosynthesis were retrospectively reviewed from 92 consecutive women (mean age, 52.4 years ± 7.9) with abnormal diagnostic or screening mammography. CEDM results were correlated with histology of ADs using cross-tabulation for statistical analysis. Predictors for risk of malignancy from CEDM characteristics (background parenchyma enhancement, degree of AD enhancement, enhancing morphology, size of enhancement, and enhancing spiculations) and patient's age were evaluated using logistic regression. We propose a sum score, termed AD score (ADS), for risk stratification and corresponding suggested BI-RADS category. RESULTS: Thirty-three of ninety-four (35.1%) of detected AD lesions were malignant. The sensitivity, specificity, PPV, and NPV of CEDM in evaluation of malignant AD are 100%, 42.6%, 48.5%, and 100%, respectively. Absence of AD enhancement on CEDM is highly indicative of no underlying malignancy. On multivariate analysis, the predictors on CEDM with statistical significance are (1) marked intensity of AD enhancement (OR, 22.6; 95%CI 3.1, 166.6; p = .002); and (2) presence of enhancing spiculations (OR, 9.1; 95%CI 2.2, 36.5; p = .002). A prediction model whose scores (ADS) given by ranking of OR of all predictors with AUC of 0.934 and Brier score of 0.0956 was developed. CONCLUSION: ADS-based lesion characterization on CEDM enables risk assessment of tomosynthesis-detected AD lesions. KEY POINTS: • Architecture distortions presenting with marked enhancement intensity and presence of enhancing spiculations are highly associated with risk of malignancy. • Absence of architecture distortion enhancement in minimal or mild background parenchyma enhancement on CEDM indicates low risk of breast malignancy (NPV = 100%).

Kinetic patterns of benign and malignant breast lesions on contrast enhanced digital mammogram.

PURPOSE: To evaluate the kinetic patterns of benign and malignant breast lesions using contrast-enhanced digital mammogram (CEDM). METHODS: Women with suspicious breast lesions on mammography or ultrasound were enrolled. Single-view mediolateral oblique (MLO) CEDM of an affected breast was acquired at 2, 3, 4, 7, and 10 min after injection of contrast agent. Three readers visually and semi-quantitatively analyzed the enhancement of suspicious lesions. The kinetic pattern of each lesion was classified as persistent, plateau, or washout over two time intervals, 2-4 min and 2-10 min, by comparing the signal intensity at the first time interval with that at the second. RESULTS: There were 73 malignant and 75 benign lesions in 148 patients (mean age: 52 years). Benign and malignant breast lesions showed the highest signal intensity at 3 min and 2 min, respectively. Average areas under receiver operating characteristic (ROC) curve for diagnostic accuracy based on lesion enhancement at different time points were 0.73 at 2 min, 0.72 at 3 min, 0.69 at 4 min, 0.67 at 7 min, and 0.64 at 10 min. Diagnostic performance was significantly better at 2, 3, and 4 min than at 7 and 10 min (all p < 0.05). A washout kinetic pattern was significantly associated with malignant lesions at 2-4 min and 2-10 min frames according to two of the three readers' interpretations (all p ≤ 0.001). CONCLUSION: Applications of optimal time intervals and kinetic patterns show promise in differentiation of benign and malignant breast lesions on CEDM.

Breast cancer screening with digital breast tomosynthesis - 4 year experience and comparison with national data.

BACKGROUND: To determine if mammography combined with digital breast tomosynthesis (DBT), leads to superior performance in screening for breast cancer compared to digital mammography (DM) alone. METHODS: We retrospectively collected data from A) the results of population-based mammography-screening provided by the National Cancer Registry in Taiwan, and B) the results from all screening mammography performed with DBT from 2012 through 2015 at Kaohsiung Veterans General Hospital (VGHKS) since the institution of DBT at the end of 2011. This was compared data from 3 years with DM performed prior to DBT implementation. We calculated the results of medical audit of VGHKS and compared this with national data. Fisher's exact test is applied. RESULTS: VGHKS data demonstrated a higher cancer detection rate (CDR) and positive predictive value 1 (PPV 1) than the national average. Most prominently in the year 2014, our CDR was 120% better than that of the national average. CDR ranged from 6.3 to 8.1‰ prior to the introduction of DBT, and following DBT implementation this improved to 8.5-11.4‰, reflecting a mean increase of 32.2%. Early cancer detection was 50% higher and node negative rate was 25% higher than the national average of latest year. A 17.8% reduction in recall rate (RR) was achieved due to a decrease in unnecessary recall. CONCLUSION: There was a 32.2% increase in CDR and a 17.8% decrease in RR when DBT was used as an adjunct to DM, as compared to DM alone. CDRs were approximately twofold better than national average data. DBT was more effective at detecting cancer in ductal carcinoma in situ and stage 1.

3D MRI for Quantitative Analysis of Quadrant Percent Breast Density: Correlation with Quadrant Location of Breast Cancer.

RATIONALE AND OBJECTIVES: Breast cancer occurs more frequently in the upper outer (UO) quadrant, but whether this higher cancer incidence is related to the greater amount of dense tissue is not known. Magnetic resonance imaging acquires three-dimensional volumetric images and is the most suitable among all breast imaging modalities for regional quantification of density. This study applied a magnetic resonance imaging-based method to measure quadrant percent density (QPD), and evaluated its association with the quadrant location of the developed breast cancer. MATERIALS AND METHODS: A total of 126 cases with pathologically confirmed breast cancer were reviewed. Only women who had unilateral breast cancer located in a clear quadrant were selected for analysis. A total of 84 women, including 47 Asian women and 37 western women, were included. An established computer-aided method was used to segment the diseased breast and the contralateral normal breast, and to separate the dense and fatty tissues. Then, a breast was further separated into four quadrants using the nipple and the centroid as anatomic landmarks. The tumor was segmented using a computer-aided method to determine its quadrant location. The distribution of cancer quadrant location, the quadrant with the highest QPD, and the proportion of cancers occurring in the highest QPD were analyzed. RESULTS: The highest incidence of cancer occurred in the UO quadrant (36 out of 84, 42.9%). The highest QPD was also noted most frequently in the UO quadrant (31 out of 84, 36.9%). When correlating the highest QPD with the quadrant location of breast cancer, only 17 women out of 84 (20.2%) had breast cancer occurring in the quadrant with the highest QPD. CONCLUSIONS: The results showed that the development of breast cancer in a specific quadrant could not be explained by the density in that quadrant, and further studies are needed to find the biological reasons accounting for the higher breast cancer incidence in the UO quadrant.

Endothelial cell colony forming units derived from malignant breast diseases are resistant to tumor necrosis factor-α-induced apoptosis.

Mobilisation of endothelial progenitor cells (EPCs) from the bone marrow is a crucial step in the formation of de novo blood vessels, and levels of peripheral blood EPCs have been shown to be elevated in certain malignant states. Using flow cytometry and a Hill-based colony forming unit (CFU) assay, the present study indicated that higher levels of CD34 and vascular endothelial growth factor receptor 2 (VEGFR2) double-positive EPCs, as well as increased formation of endothelial cell colony-forming units (EC-CFUs) are associated with benign and malignant breast diseases, providing possible indicators for breast disease detection. Gene expression profiles revealed a genetic difference between CD34+ VEGFR2+ EPCs and EC-CFUs. Decreased expression of tumour necrosis factor receptor 2 (TNFR2) signalling-related genes and inhibition of tumour necrosis factor (TNF)-induced signalling were demonstrated in EC-CFUs derived from patients with malignant breast disease in comparison with those from healthy controls. Interestingly, our data provided the first evidence that EC-CFUs derived from patients with malignant breast disease were resistant to TNF-α-induced apoptosis, indicating a plausible target for future therapeutic interventions.

Easily recognizable sonographic patterns of ductal carcinoma in situ of the breast.

BACKGROUND: Ductal carcinoma in situ (DCIS) is a malignant proliferation of ductal epithelium confined by the basement membrane of the involved breast ducts. The aim of this study was to categorize positive findings of DCIS of the breast on sonography. METHODS: From 2007 to 2011, 100 pathologically proven DCIS lesions were evaluated. Four sonographic patterns used to identify DCIS have been characterized as cumulus-type, coral-type, pipe-type, and miscellaneous lesions. RESULTS: The lesion numbers of nonhigh-grade and high-grade DCIS were 44 and 56, respectively. The coral type (42%) was the most commonly found lesion, followed by cumulus-type (38%), pipe-type (17%), and miscellaneous (3%) lesions. There was no significant difference between the sonographic pattern and nuclear grades. However, the coral-type group was composed of significantly more high-grade DCIS cases than the other three types (p < 0.05). CONCLUSION: Coral-, cumulus-, and pipe-type lesions are three easily recognizable sonographic findings of DCIS. Improving the breast ultrasound technique to better demonstrate the sonographic pattern is necessary to facilitate breast lesion interpretation.

Specific detection of CD133-positive tumor cells with iron oxide nanoparticles labeling using noninvasive molecular magnetic resonance imaging.

BACKGROUND: The use of ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles to visualize cells has been applied clinically, showing the potential for monitoring cells in vivo with magnetic resonance imaging (MRI). USPIO conjugated with anti-CD133 antibodies (USPIO-CD133 Ab) that recognize the CD133 molecule, a cancer stem cell marker in a variety of cancers, was studied as a novel and potent agent for MRI contrast enhancement of tumor cells. MATERIALS AND METHODS: Anti-CD133 antibodies were used to conjugate with USPIO via interaction of streptavidin and biotin for in vivo labeling of CD133-positive cells in xenografted tumors and N-ethyl-N-nitrosourea (ENU)-induced brain tumors. The specific binding of USPIO-CD133 Ab to CD133-positive tumor cells was subsequently detected by Prussian blue staining and MRI with T2-weighted, gradient echo and multiple echo recombined gradient echo images. In addition, the cellular toxicity of USPIO-CD133 Ab was determined by analyzing cell proliferation, apoptosis, and reactive oxygen species production. RESULTS: USPIO-CD133 Ab specifically recognizes in vitro and labels CD133-positive cells, as validated using Prussian blue staining and MRI. The assays of cell proliferation, apoptosis, and reactive oxygen species production showed no significant differences in tumor cells with or without labeling of USPIO-CD133 Ab. In vivo imaging of CD133-positive cells was demonstrated by intravenous injection of USPIO-CD133 Ab in mice with HT29 xenografted tumors. The MRI of HT29 xenografts showed several clusters of hypotensive regions that correlated with CD133 expression and Prussian blue staining for iron. In rat, brain tumors induced by transplacental ENU mutagenesis, several clusters of hypointensive zones were observed in CD133-expressing brain tumors by MRI and intravenously administered USPIO-CD133 Ab. CONCLUSION: Combination of USPIO-CD133 Ab and MRI is valuable in recognizing CD133-expressing tumor cells in vitro, extracellularly labeling for cell tracking and detecting CD133-expressing tumors in xenografted tumors as well as ENU-induced rat brain tumors.

Clinical evaluation of contrast-enhanced digital mammography and contrast enhanced tomosynthesis--Comparison to contrast-enhanced breast MRI.

PURPOSE: To compare the diagnostic accuracy of contrast-enhanced digital mammography (CEDM) and contrast-enhanced tomosynthesis (CET) to dynamic contrast enhanced breast MRI (DCE-MRI) using a multireader-multicase study. METHODS: Institutional review board approval and informed consents were obtained. Total 185 patients (mean age 51.3) with BI-RADS 4 or 5 lesions were evaluated before biopsy with mammography, tomosynthesis, CEDM, CET and DCE-MRI. Mediolateral-oblique and cranio-caudal views of the target breast CEDM and CET were acquired at 2 and 4 min after contrast agent injection. A mediolateral-oblique view of the non-target breast was taken at 6 min. Each lesion was scored with forced BI-RADS categories by three readers. Each reader interpreted lesions in the following order: mammography, tomosynthesis, CEDM, CET, and DCE-MRI during a single reading session. RESULTS: Histology showed 81 cancers and 144 benign lesions in the study. Of the 81 malignant lesions, 44% (36/81) were invasive and 56% (45/81) were non-invasive. Areas under the ROC curve, averaged for the 3 readers, were as follows: 0.897 for DCE-MRI, 0.892 for CET, 0.878 for CEDM, 0.784 for tomosynthesis and 0.740 for mammography. Significant differences in AUC were found between the group of contrast enhanced modalities (CEDM, CET, DCE-MRI) and the unenhanced modalities (all p<0.05). No significant differences were found in AUC between DCE-MRI, CET and CEDM (all p>0.05). CONCLUSION: CET and CEDM may be considered as an alternative modality to MRI for following up women with abnormal mammography. All three contrast modalities were superior in accuracy to conventional digital mammography with or without tomosynthesis.

Clinical roles of breast 3T MRI, FDG PET/CT, and breast ultrasound for asymptomatic women with an abnormal screening mammogram.

BACKGROUND: Magnetic resonance imaging (MRI) and fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) show promise for molecular cancer imaging. We evaluated 3T MRI, FDG PET/CT, and ultrasound images for asymptomatic women with an abnormal screening mammogram. METHODS: The Institutional Review Board of Kaohsiung Veterans General Hospital (Kaohsiung, Taiwan) approved the study. Patients provided written informed consent. A total of 11,865 screening mammograms of 118,65 women were performed at our facility between January 2011 and December 2012. Fifty-three asymptomatic women (mean age, 53.3 years) whose screening mammograms had a Breast Imaging Reporting and Data System (BI-RADS) category of 4 or 5 were ultimately enrolled in this study. Breast 3T MRI, FDG PET/CT, and breast ultrasound were performed before biopsy. All imaging modalities were compared by lesion-by-lesion analyses. RESULTS: Fifty-nine breast lesions (28 malignant and 31 benign lesions) from 53 women were analyzed. The sensitivity, specificity, and accuracy for 28 breast cancers were 96%, 77%, and 86%, respectively, for breast 3T MRI; 50%, 100%, and 76%, respectively, for FDG PET,CT; and 61%, 87%, and 74%, respectively, for breast ultrasound. One 0.8-cm invasive breast cancer was missed by the screening mammogram, but detected by breast 3T MRI and FDG PET/CT. The sensitivity for detecting breast cancer was significantly higher with MRI than with PET/CT or ultrasound (for all, p < 0.01). The specificity for detecting breast cancer was significantly higher for PET/CT than for breast MRI (p = 0.02). The sensitivity exhibited by 3T breast MRI and FDG PET/CT for 16 noninvasive breast cancers was 94% and 25%, respectively. CONCLUSION: On screening mammograms, breast 3T MRI showed higher sensitivity but less specificity than FDG PET/CT for detecting asymptomatic breast cancers.

FDG-PET/CT detection of very early breast cancer in women with breast microcalcification lesions found in mammography screening.

INTRODUCTION: To assess the efficacy of positron emission tomography/computed tomography with the glucose analogue 2-[(18) F]fluoro-2-deoxy-D-glucose (FDG-PET/CT) in Taiwanese women with early breast cancer detected by mammography screening. METHODS: Dual-time-point imaging of whole-body supine and breast prone scans using FDG-PET/CT were performed sequentially in the pre-operative stage. RESULTS: A total of 11,849 patients underwent screening mammography, of whom 1,209 (10.2%) displayed positive results. After further investigation, 54 patients underwent FDG-PET/CT. Post-operative pathology examinations revealed malignancies in 26 lesions, including invasive breast cancer in 11 cases and non-invasive breast cancer in 15 cases, as well as benign disease in 30 lesions. The FDG-PET/CT findings from the whole-body scans were positive for 9 of 11 invasive breast cancers (81.8%) and 3 of 15 non-invasive cancers (20%), and they were negative for all benign lesions. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of FDG-PET/CT with whole-body supine imaging were 46.2%, 100%, 100% and 68.2%, respectively. Breast prone imaging revealed another patient with ductal carcinoma in situ, increasing the sensitivity to 50%. Importantly, positive PET findings were significantly correlated with tumour histology (P = 0.006), tumour size (P = 0.039) and Ki-67 expression (P = 0.011). CONCLUSIONS: FDG-PET/CT with whole-body scanning demonstrated high sensitivity to invasive breast cancer, limited sensitivity to non-invasive breast cancer, and high specificity for breast cancer. FDG-PET/CT might be useful for differentiating tumour invasiveness. However, the good PPV but poor NPV do not allow the physician to discard the biopsy.

Gadoxetic acid-enhanced MRI and sonoelastography: non-invasive assessments of chemoprevention of liver fibrosis in thioacetamide-induced rats with Sho-Saiko-To.

BACKGROUND: This study aimed to compare the performance of gadoxetic acid -enhanced magnetic resonance imaging (MRI) and sonoelastography in evaluating chemopreventive effects of Sho-Saiko-To (SST) in thioacetamide (TAA)-induced early liver fibrosis in rats. MATERIALS AND METHODS: Ten of Sprague-Dawley rats receiving TAA (200 mg/kg of body weight) intraperitoneal injection were divided into three groups: Group 1 (TAA only, n = 3), Group 2 (TAA +0.25 g/kg SST, n = 4) and Group 3 (TAA+1 g/kg SST, n = 3). Core needle liver biopsy at week 2 and liver specimens after sacrifice at week 6 confirmed liver fibrosis using histological examinations, including Sirius red staining, Ishak and Metavir scoring systems. Gadoxetic acid-enhanced MRI and shear-wave sonoelastography were employed to evaluate liver fibrosis. The expression of hepatic transporter organic anion transporter 1 (Oatp1), multidrug-resistant protein 2 (Mrp2) and alpha-smooth muscle actin (α-Sma) were also analyzed in each group by immunohistochemistry (IHC) and Western blot. RESULTS: According to histological grading by Sirius red staining, Ishak scores of liver fibrosis in Groups 1, 2 and 3 were 3, 2 and 1, respectively. As shown in gadoxetic acid-enhanced MRI, the ratio of relative enhancement was significantly lower in Group 1 (1.87 ± 0.21) than in Group 2 of low-dose (2.82 ± 0.25) and Group 3 of high-dose (2.72 ± 0.12) SST treatment at 10 minutes after gadoxetic acid intravenous injection (p < 0.05). Sonoelastography showed that the mean difference before and after experiments in Groups 1, 2 and 3 were 4.66 ± 0.1, 4.4 ± 0.57 and 3 ± 0.4 KPa (p < 0.1), respectively. Chemopreventive effects of SST reduced the Mrp2 protein level (p < 0.01) but not Oatp1 and α-Sma levels. CONCLUSION: Sonoelastography and gadoxetic acid-enhanced MRI could monitor the treatment effect of SST in an animal model of early hepatic fibrosis.

The outcome of a quality-controlled mammography screening program: experience from a population-based study in Taiwan.

BACKGROUND: A greater policy of emphasis on the early detection and treatment of breast cancer is prevalent among developed countries. To raise the screening performance with a potentially decreased mortality rate, it is crucial to evaluate and analyze the screening outcome after implementation. We report the clinical outcome of an 8-year nationwide mammography screening in Taiwan to help share our statistical information on breast screening worldwide, especially in Asia. METHODS: Taiwan has provided nationwide, free, biennial mammographic screening since 2004. A total of 2,392,789 consecutive screening mammography examinations were performed during this study period for women aged 50-69 years (2006-2009) and 45-69 years (from December 2009 onwards). The screening covers 33.2% of the target population in the most recent 2 years. The workload of every screening radiologist, the overall recall rate, positive predictive value (PPV1), cancer detection rate (CDR), cancer incidence rate (CIR) from the screening, 1-year interval cancer, sensitivity, and specificity of the screening mammography are calculated, and compared with the American College of Radiology (ACR) recommendation level and/or those of other screening mammographic series. RESULTS: The CDRs (%) and CIRs (%) increased from 3.94-4.08 and 4.80-5.04 to 4.71-5.04 and 5.71 after 2009, implying a high occurrence of breast cancer in the younger age group of 45-49 years. The recall rates (9.3-10.0%) in this review are within the ACR recommendation range (<10%) and the PPV1 has also reached the ACR recommended level (>5%) in the most recent 2 years. The improvement of the screening performance may be attributed to our peer auditing review and education program. The sensitivity of our screening mammography is slightly lower than that of the ACR recommended level (>85%), which is still comparable to the results of the Vermont area in the USA. Although the workload (screenees/screeners) for every radiologist each year has increased from 150 in 2004 to 1360 in 2012, it does not seem to worsen the quality outcome of this screening program. CONCLUSION: From the outcome review of this national mammography screening, there is still room to ameliorate our performance through comprehensive and continued education, to improve the competence of cancer detection and decrease false negative (FN) cases.

Ubiquitin-conjugating enzyme UBE2C is highly expressed in breast microcalcification lesions.

Ubiquitin-conjugating enzyme 2C (UBE2C) contributes to ubiquitin-mediated proteasome degradation of cell cycle progression in breast cancer. Microcalcification (MC) is the most common mammographic feature of early breast cancer. In this study, we evaluated whether UBE2C could be a tumor marker of early breast cancer with MC found on screening mammography. UBE2C protein and mRNA expression were measured in breast core biopsy pairs of MC and adjacent non-MC breast tissue from each subject. Immunohistochemistry revealed UBE2C positivity in 69.4% of MC samples and 77.6% negativity in non-MC samples (p<0.0001). On RT-qPCR, 56.1% of malignant MC lesion samples showed high mRNA level of UBE2C and 80% of benign MC lesion samples showed a low level of UBE2C (p = 0.1766). We investigated the carcinogenic role of UBE2C in MCF-7 breast cancer cells with UBE2C knockdown; UBE2C knockdown downregulated cell proliferation and activated the cellular apoptosis pathway to inhibit cell colony formation. Furthermore, UBE2C expression was associated with that of carcinogenic genes human epidermal growth factor receptor type 2 (HER2), cellular c-Ki-ras2 proto-oncogene (KRAS), vascular endothelial growth factor (VEGF), CXC chemokine receptor 4 (CXCR4), C-C motif chemokine 5 (CCL5), neural precursor cell expressed, developmentally downregulated 9 (NEDD9) and Ras homolog family member C (RhoC). UBE2C may be a marker for diagnosis of nonpalpable breast lesions but not benign or malignant tumors in mammography core biopsies. Suppression of UBE2C may be a potential therapy target in breast cancer.