Drug and xenobiotic metabolizing enzymes (DXME) play important roles in drug responses and carcinogenesis. Recent studies have found that expression of DXME in cancer cells significantly affects drug clearance and the onset of drug resistance. In this study we compared the expression of DXME in breast tumor tissue samples from patients representing three ethnic groups: Caucasian Americans (CA), African Americans (AA), and Asian Americans (AS). We further combined DXME gene expression data with eQTL data from the GTEx project and with allele frequency data from the 1000 Genomes project to identify SNPs that may be associated with differential expression of DXME genes. We identified substantial differences among CA, AA, and AS populations in the expression of DXME genes and in activation of pathways involved in drug metabolism, including those involved in metabolizing chemotherapy drugs that are commonly used in the treatment of breast cancer. These data suggest that differential expression of DXME may associate with health disparities in breast cancer outcomes observed among these three ethnic groups. Our study suggests that development of personalized treatment strategies for breast cancer patients could be improved by considering both germline genotypes and tumor specific mutations and expression profiles related to DXME genes.
17 April 2020 in Journal of Medical Internet Research
Background: The internet allows patients to easily look for health information. However, how Chinese patients with breast cancer use the internet has rarely been investigated, and there is a scarcity of information about the influence of internet use on survival. Objective: This observational study aimed to investigate the details of online medical information searching by Chinese patients with breast cancer and to determine whether internet use has any survival benefits. Methods: Patients who were diagnosed with invasive breast cancer at Peking Union Medical College Hospital between January 2014 and December 2015 were enrolled. We obtained information on their internet-searching behavior and gathered data from the patients’ medical and follow-up records. The associations between internet use and other clinic-pathological factors were analyzed. A Cox proportional-hazards model and the Kaplan-Meier method were used for disease-free survival (DFS) analyses. Results: A total of 973 patients with invasive breast cancer who underwent definitive surgery took part in the study. Among them, 477 cases (49.0%) performed web-based breast cancer information searching before the initial treatment. A multivariate logistic regression analysis suggested that web-based breast cancer information searching was significantly associated with younger age (odds ratio [OR] 0.95, 95% CI 0.94-0.97, P<.001), higher education level (OR 1.37, 95% CI 1.01–1.86, P=.04), and breast conserving surgery (OR 1.35, 95% CI 1.04-1.77, P=.03). Baidu (73.4%, 350/477) and WeChat (66.7%, 318/477) were the two most popular online information sources for breast cancer; however, only 44.9% (214/477) felt satisfied with the online information. In contrast to the nonweb searching group, the web-using patients who were satisfied with online information showed significantly improved DFS (hazard ratio 0.26; 95% CI 0.08-0.88, P=.03). Conclusions: The patients who were most likely to search the internet for breast cancer information were younger and well-educated, and they were more likely to have breast conserving therapy. Web-using patients who were satisfied with the internet information showed significantly improved DFS. Patients should browse credible websites offering accurate and updated information, and website developers should provide high-quality and easy-to-understand information to better meet the needs of patients with breast cancer.
We aimed to determine whether the detection-to-treatment interval of non-symptomatic breast cancer is associated with factors that can predict survival outcomes. A retrospective review of the Breast Surgery Department Database at Peking Union Medical College Hospital (PUMCH) was performed, and a total of 1084 non-symptomatic invasive breast cancer patients were included. The findings revealed that detection-to-treatment interval was significantly longer for women who were older (p = 0.001), lived in rural areas (p = 0.024), had lower education (p = 0.024), and had detection in other institutions (p = 0.006). Other sociodemographic and clinicopathological characteristics were not associated to longer interval. A median follow-up of 35 months (range: 6–60 months) was carried out and a long delay at more than 90 days did not significantly decrease the DFS (univariate, P = 0.232; multivariate, P = 0.088). For triple negative breast cancer, there was a worse DFS if the interval was longer than 90 days both in multivariate analysis (hazard ratio [HR] = 3.40; 95% CI, 1.12–10.35; P = 0.031) and univariate analysis (HR = 2.86; 95% CI, 1.03–7.91; P = 0.042). Further studies on care before initial treatment of non-symptomatic breast cancers are warranted.
This study aimed to determine whether there is an association between mammographic casting-type calcification and other prognostic factors for invasive breast cancer. We also assessed whether casting-type calcification could be an independent prognostic factor. Invasive breast cancer patient information from January 2010 and January 2013 was retrospectively reviewed. The associations between mammographic casting-type calcification and other clinicopathological factors, including tumor size, node status, grade, progesterone receptor (PR) status, estrogen receptor (ER) status, and human epidermal growth factor receptor 2 (HER2) status, were analyzed. The Kaplan–Meier method and a Cox proportional hazards model were used for survival analyses of disease-free survival (DFS) and overall survival (OS). A total of 1155 invasive breast cancer patients who underwent definitive surgery were included, and 136 cases (11.8%) had casting-type calcification on mammography. In multivariate logistic regression, casting-type calcification was significantly associated with axillary node metastasis, ER-negativity, and HER2 overexpression. Casting-type calcification significantly decreased OS and DFS after a median follow-up of 60 months. This result remained after adjusting other prognostic factors in the multivariate analysis. Casting-type calcification is significantly linked to axillary node metastasis, ER-negativity and HER2 overexpression. Casting-type calcification is therefore an independent prognostic factor for breast cancer patients.
Background: Establishment of cohesion 1 homolog 2 (ESCO2) plays important roles in the regulation of cohesion and genomic stability and has been implicated in human cancers. Yet, its clinical significance and biological function in colorectal cancer (CRC) are unknown. Methods: The expression of ESCO2 was examined by quantitative real-time PCR, Western blot, and immunohistochemistry. The role of ESCO2 in the tumor metastasis of CRC and the related mechanisms were investigated using in vitro and in vivo models. Results: In this study, we show that low expression of ESCO2 in CRC was closely correlated with lymphatic and distant metastasis. Patients with low ESCO2 expression experienced shorter overall survival and disease-free survival in two independent cohorts containing a total of 587 CRC cases. ESCO2 overexpression suppressed, whereas ESCO2 knockdown promoted cell migration in vitro and tumor metastasis in vivo via modulation of epithelial–mesenchymal transition (EMT) process. Mechanistically, ESCO2 inhibited the transcriptional activity of MMP2 promoter to downregulate its expression. Reexpression of MMP2 partially attenuated the ESCO2-mediated malignant phenotypes. Conclusion: Collectively, our data suggest that ESCO2 serves as a potential prognostic factor and exerts antimetastatic activity in CRC.
Background: This preliminary study aimed to examine the feasibility of sentinel lymph node biopsy (SLNB) using contrast-enhanced ultrasound (CEUS) vs. indocyanine green fluorescence (ICG), combined with blue dye in patients with breast cancer. Methods: This was a retrospective study of consecutive female patients with invasive stage I-III (based on pre-operative physical examination and imaging) primary breast cancer at the Peking Union Medical College Hospital between 01/2013 and 01/2015 who underwent preoperative SLNB by ICG + blue dye or CEUS + blue dye. The numbers of detected SLNs, detection rates, and recurrence-free survival (RFS) rates were compared between the two groups. Results: A total of 443 patients were included. The detection rates of SLNs in the CEUS + blue dye and ICG + blue dye groups were 98.4 and 98.1%, respectively (P = 0.814). The average numbers of SLNs detected per patient showed no significant difference between the two groups (3.06 ± 1.33 and 3.12 ± 1.31 in the CEUS + blue dye and ICG + blue dye groups, respectively; P = 0.659). After a median follow-up of 46 months, five patients in the CEUS + blue dye group and 15 in the ICG + blue dye group had recurrence. RFS rates showed no significant difference (P = 0.55). Conclusion: This preliminary study suggests that CEUS + blue dye and ICG + blue dye are both feasible for SLN detection in breast cancer.