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

Intra-operative Radiation Therapy versus Whole Breast External Beam Radiotherapy: A Comparison of Patient-Reported Outcomes

Introduction. This project sought to compare patient-reported outcomes between patients who received intra-operative radiation therapy (IORT) and those who qualified for IORT but received whole-breast external beam radiation therapy (EBRT) following breast-conserving surgery (BCS). Methods. Three scales from the BREAST-Q Breast Cancer BCT Module Version 2.0 questionnaire were used to collect patient-reported outcomes regarding post-operative physical well-being of the chest, post-operative satisfaction with breast cosmesis and post-operative adverse effects of radiation. Results. Patients who received EBRT travelled farther on average than patients who received IORT to complete treatment. Respondents who received IORT reported better physical well-being of the chest than those who received EBRT. Regression reveals that the respondent’s age was the determining factor in the difference between IORT and EBRT post-operative physical well-being scores, where younger patients report poorer well-being. There was no difference in patient-reported outcomes regarding post-operative satisfaction with breast cosmesis or adverse effects of radiation. Conclusions. This study suggests that patients who received IORT report better physical well-being of the chest than patients who received EBRT. There appears to be a relationship between age and physical well-being of chest. This study suggests that there is no difference in patient-reported outcomes concerning post-operative satisfaction with breast cosmesis or post-operative adverse effects of radiation between patients who received IORT and those who received EBRT

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

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. Electronic supplementary material The online version of this article (doi:10.1186/s13058-015-0630-z) contains supplementary material, which is available to authorized users