Depression and family support in breast cancer patients

MTS, migration and invasion assays in DCIS.COM cells that were previously transduced with scrambled control (Control) or BCL9 KD shRNA. The control cells and BCL9 KD cells were re-transduced with empty vector (EV), BCL9 overexpression (BCL9-OE) and BCL9 KD. BCL9-OE was achieved by transduction using the PCDH-BCL9 (BCL9-OE) acquired from Dr. Carrasco [11]. A Western blot analysis was performed using anti-BCL9, anti-vimentin, anti-E-cadherin antibodies, and anti-β-actin as a loading control. B MTS assay on control cells transduced with EV (control + EV), or BCL9-OE (control + BCL9-OE), BCL9-KD transduced with EV (BCL9 KD + EV), and BCL9-KD transduced with BCL9-OE (BCL9 KD + BCL9-OE). Bar graphs represent mean absorbance at 490 nm normalized to control ± standard error of the mean (SEM) (n = 6). C, D Representative images of the migration and invasion assays. Bar graph represents percent area of cells migrated (left) and invaded (right) under the membrane after 24 h. Invasion and migration were determined by ImageJ analysis of microscopic images per sample, the data are mean values normalized to control ± SEM (n = 3). E TopFlash and FopFlash reporter activity in DCIS.COM transduced as above that were either treated with Wnt3A or control conditioned medium (CM). Data represent mean ± SEM (n = 3, letters indicate statistically significant difference). (PDF 964 kb

Expression profiling of in vivo ductal carcinoma in situ progression models identified B cell lymphoma-9 as a molecular driver of breast cancer invasion

Abstract Introduction There are an estimated 60,000 new cases of ductal carcinoma in situ (DCIS) each year. A lack of understanding in DCIS pathobiology has led to overtreatment of more than half of patients. We profiled the temporal molecular changes during DCIS transition to invasive ductal carcinoma (IDC) using in vivo DCIS progression models. These studies identified B cell lymphoma-9 (BCL9) as a potential molecular driver of early invasion. BCL9 is a newly found co-activator of Wnt-stimulated β-catenin-mediated transcription. BCL9 has been shown to promote progression of multiple myeloma and colon carcinoma. However BCL9 role in breast cancer had not been previously recognized. Methods Microarray and RNA sequencing were utilized to characterize the sequential changes in mRNA expression during DCIS invasive transition. BCL9-shRNA knockdown was performed to assess the role of BCL9 in in vivo invasion, epithelial-mesenchymal transition (EMT) and canonical Wnt-signaling. Immunofluorescence of 28 patient samples was used to assess a correlation between the expression of BCL9 and biomarkers of high risk DCIS. The cancer genome atlas data were analyzed to assess the status of BCL9 gene alterations in breast cancers. Results Analysis of BCL9, by RNA and protein showed BCL9 up-regulation to be associated with DCIS transition to IDC. Analysis of patient DCIS revealed a significant correlation between high nuclear BCL9 and pathologic characteristics associated with DCIS recurrence: Estrogen receptor (ER) and progesterone receptor (PR) negative, high nuclear grade, and high human epidermal growth factor receptor2 (HER2). In vivo silencing of BCL9 resulted in the inhibition of DCIS invasion and reversal of EMT. Analysis of the TCGA data showed BCL9 to be altered in 26 % of breast cancers. This is a significant alteration when compared to HER2 (ERBB2) gene (19 %) and estrogen receptor (ESR1) gene (8 %). A significantly higher proportion of basal like invasive breast cancers compared to luminal breast cancers showed BCL9 amplification. Conclusion BCL9 is a molecular driver of DCIS invasive progression and may predispose to the development of basal like invasive breast cancers. As such, BCL9 has the potential to serve as a biomarker of high risk DCIS and as a therapeutic target for prevention of IDC

Automated Breast Ultrasound in Breast Cancer Screening of Women With Dense Breasts: Reader Study of Mammography-Negative and Mammography-Positive Cancers.

© 2016 American Roentgen Ray Society. OBJECTIVE. The objective of our study was to assess and compare, in a reader study, radiologists\u27 performance in the detection of breast cancer using full-field digital mammography (FFDM) alone and using FFDM with 3D automated breast ultrasound (ABUS). MATERIALS AND METHODS. In this multireader, multicase, sequential-design reader study, 17 Mammography Quality Standards Act-qualified radiologists interpreted a cancerenriched set of FFDM and ABUS examinations. All imaging studies were of asymptomatic women with BI-RADS C or D breast density. Readers first interpreted FFDM alone and subsequently interpreted FFDM combined with ABUS. The analysis included 185 cases: 133 noncancers and 52 biopsy-proven cancers. Of the 52 cancer cases, the screening FFDM images were interpreted as showing BI-RADS 1 or 2 findings in 31 cases and BI-RADS 0 findings in 21 cases. For the cases interpreted as BI-RADS 0, a forced BI-RADS score was also given. Reader performance was compared in terms of AUC under the ROC curve, sensitivity, and specificity. RESULTS. The AUC was 0.72 for FFDM alone and 0.82 for FFDM combined with ABUS, yielding a statistically significant 14% relative improvement in AUC (i.e., change in AUC = 0.10 [95% CI, 0.07-0.14]; p \u3c 0.001). When a cutpoint of BI-RADS 3 was used, the sensitivity across all readers was 57.5% for FFDM alone and 74.1% for FFDM with ABUS, yielding a statistically significant increase in sensitivity (p \u3c 0.001) (relative increase = 29%). Overall specificity was 78.1% for FFDM alone and 76.1% for FFDM with ABUS (p = 0.496). For only the mammography-negative cancers, the average AUC was 0.60 for FFDM alone and 0.75 for FFDM with ABUS, yielding a statistically significant 25% relative improvement in AUC with the addition of ABUS (p \u3c 0.001). CONCLUSION. Combining mammography with ABUS, compared with mammography alone, significantly improved readers\u27 detection of breast cancers in women with dense breast tissue without substantially affecting specificity

Automated breast ultrasound in breast cancer screening of women with dense breasts: Reader study of mammography-negative and mammography-positive cancers

© 2016 American Roentgen Ray Society. OBJECTIVE. The objective of our study was to assess and compare, in a reader study, radiologists\u27 performance in the detection of breast cancer using full-field digital mammography (FFDM) alone and using FFDM with 3D automated breast ultrasound (ABUS). MATERIALS AND METHODS. In this multireader, multicase, sequential-design reader study, 17 Mammography Quality Standards Act-qualified radiologists interpreted a cancerenriched set of FFDM and ABUS examinations. All imaging studies were of asymptomatic women with BI-RADS C or D breast density. Readers first interpreted FFDM alone and subsequently interpreted FFDM combined with ABUS. The analysis included 185 cases: 133 noncancers and 52 biopsy-proven cancers. Of the 52 cancer cases, the screening FFDM images were interpreted as showing BI-RADS 1 or 2 findings in 31 cases and BI-RADS 0 findings in 21 cases. For the cases interpreted as BI-RADS 0, a forced BI-RADS score was also given. Reader performance was compared in terms of AUC under the ROC curve, sensitivity, and specificity. RESULTS. The AUC was 0.72 for FFDM alone and 0.82 for FFDM combined with ABUS, yielding a statistically significant 14% relative improvement in AUC (i.e., change in AUC = 0.10 [95% CI, 0.07-0.14]; p \u3c 0.001). When a cutpoint of BI-RADS 3 was used, the sensitivity across all readers was 57.5% for FFDM alone and 74.1% for FFDM with ABUS, yielding a statistically significant increase in sensitivity (p \u3c 0.001) (relative increase = 29%). Overall specificity was 78.1% for FFDM alone and 76.1% for FFDM with ABUS (p = 0.496). For only the mammography-negative cancers, the average AUC was 0.60 for FFDM alone and 0.75 for FFDM with ABUS, yielding a statistically significant 25% relative improvement in AUC with the addition of ABUS (p \u3c 0.001). CONCLUSION. Combining mammography with ABUS, compared with mammography alone, significantly improved readers\u27 detection of breast cancers in women with dense breast tissue without substantially affecting specificity

Right Ventricular Function and Pulmonary Coupling in Patients With Heart Failure and Preserved Ejection Fraction

Background: Limited data exist to characterize novel measures of right ventricular (RV) function and the coupling to pulmonary circulation in patients with heart failure and preserved left ventricular ejection fraction (HFpEF). Objectives: This study sought to assess the clinical implications of RV function, the association with N-terminal pro–B-type natriuretic peptide, and the risk for adverse events among patients with HFpEF. Methods: This study analyzed measures of RV function by assessing absolute RV free wall longitudinal strain (RVFWLS) and its ratio to estimated pulmonary artery systolic pressure (PASP) (RVFWLS/PASP ratio) in 528 patients (mean age 74 ± 8 years, 56% female) with adequate echocardiographic images quality enrolled in the PARAGON-HF trial. Associations with baseline N-terminal pro–B-type natriuretic peptide and with total HF hospitalizations and cardiovascular death were assessed, after accounting for confounders. Results: Overall, 311 patients (58%) had evidence of RV dysfunction, defined as absolute RVFWLS &lt;20%, and among the 388 patients (73%) with normal tricuspid annular planar systolic excursion and RV fractional area change, more than one-half showed impaired RV function. Lower values of RVFWLS and RVFWLS/PASP ratios were significantly associated with higher circulating N-terminal pro–B-type natriuretic peptide. With a median follow-up of 2.8 years, there were 277 total HF hospitalizations and cardiovascular deaths. Both absolute RVFWLS (HR: 1.39; 95% CI: 1.05-1.83; P = 0.018) and RVFWLS/PASP ratio (HR: 1.43; 95% CI: 1.13-1.80; P = 0.002) were significantly associated with the composite outcome. Treatment effect of sacubitril/valsartan was not modified by measures of RV function. Conclusions: Worsening RV function and its ratio to pulmonary pressure is common and significantly associated with an increased risk of HF hospitalizations and cardiovascular death in patients with HFpEF.</p

Assessing improvement in detection of breast cancer with three-dimensional automated breast US in women with dense breast tissue: The somoinsight study

© RSNA, 2014. Purpose: To determine improvement in breast cancer detection by using supplemental three-dimensional (3D) automated breast (AB) ultrasonography (US) with screening mammography versus screening mammography alone in asymptomatic women with dense breasts. Materials and Methods: Institutional review board approval and written informed consent were obtained for this HIPAA-compliant study. The SomoInsight Study was an observational, multicenter study conducted between 2009 and 2011. A total of 15 318 women (mean age, 53.3 years ± 10 [standard deviation]; range, 25-94 years) presenting for screening mammography alone with heterogeneously (50%-75%) or extremely (\u3e75%) dense breasts were included, regardless of further risk characterization, and were followed up for 1 year. Participants underwent screening mammography alone followed by an AB US examination; results were interpreted sequentially. McNemar test was used to assess differences in cancer detection. Results: Breast cancer was diagnosed at screening in 112 women: 82 with screening mammography and an additional 30 with AB US. Addition of AB US to screening mammography yielded an additional 1.9 detected cancers per 1000 women screened (95% confidence interval [CI]: 1.2, 2.7; P , .001). Of cancers detected with screening mammography, 62.2% (51 of 82) were invasive versus 93.3% (28 of 30) of additional cancers detected with AB US (P \u3c .001). Of the 82 cancers detected with either screening mammography alone or the combined read, 17 were detected with screening mammography alone. Of these, 64.7% (11 of 17) were ductal carcinoma in situ versus 6.7% (two of 30) of cancers detected with AB US alone. Sensitivity for the combined read increased by 26.7% (95% CI: 18.3%, 35.1%); the increase in the recall rate per 1000 women screened was 284.9 (95% CI: 278.0, 292.2; P \u3c .001). Conclusion: Addition of AB US to screening mammography in a generalizable cohort of women with dense breasts increased the cancer detection yield of clinically important cancers, but it also increased the number of false-positive results