Breast Cancer Attributable Costs in Germany: A Top-Down Approach Based on Sickness Funds Data

Background

Breast cancer is the leading cause of death from cancer among women in Germany. Despite its clinical and economic relevance, no attributable costs for breast cancer have been reported for Germany so far. The objective of this study is to estimate age-specific breast cancer attributable health expenditures for Germany.

Methods

Sickness fund data from 1999 representing about 26 million insured (i.e. 32% of the total German population) have been analysed using generalized additive models and the error propagation law. Costs have been inflated to 2010.

Results

Breast cancer attributable costs decreased with age. Among breast cancer patients aged 30–45 years, about 90% of all health expenditures were due to breast cancer, whereas in breast cancer patients aged 80–90 years, about 50% were due to breast cancer. Breast cancer attributable costs amounted to about €9,000 annually for patients below 55 years of age and declined to about €3,000 in 90-year-old breast cancer patients.

Conclusion

This analysis provides estimates of attributable breast cancer costs in Germany. Compared with the international literature, the estimates were plausible but had a tendency to underestimate breast cancer attributable costs.     

Screening and self examination for breast cancer.

Breast cancer is the major form of cancer in women, with nearly 30,000 new cases and over 15,000 deaths in the United Kingdom each year. Breast screening by mammography has been shown in randomised trials to reduce mortality from breast cancer in women aged 50 and over. An NHS breast screening programme has been in operation in the United Kingdom since 1988. Its aim is to reduce mortality from breast cancer by 25% in the population of women invited to be screened. The uptake of mammography among the eligible population may be the single most important determinant if the programme is to be effective. Primary care teams have an important part to play in encouraging women to attend for screening and in providing information, advice, and reassurance at all stages of the screening process. To date, routine breast self examination has not been shown to be an effective method of screening for breast cancer and should not therefore be promoted as a primary screening procedure. There is, however, a case to be made for women to become more "breast aware."     

A novel long non-coding RNA AC073352.1 promotes metastasis and angiogenesis via interacting with YBX1 in breast cancer

Breast cancer is the major cause of cancer death worldwide in women. Patients with metastasis have poor prognosis and the mechanisms of breast cancer metastasis are not completely understood. Long non-coding RNAs (lncRNAs) have been shown to have crucial roles in breast cancer development and progression. However, the underlying mechanisms by which lncRNA-driven breast cancer metastasis are unknown. The main objective of this paper is to explore a functional lncRNA and its mechanisms in breast cancer. Here we identified a novel lncRNA AC073352.1 that was significantly upregulated in breast cancer tissues and was associated with advanced TNM stages and poor prognosis in breast cancer patients. In addition, AC073352.1 was found to promote the migration and invasion of breast cancer cells in vitro and enhance breast cancer metastasis in vivo. Mechanistically, we elucidated that AC073352.1 interacted with YBX1 and stabilized its protein expression. Knock down of YBX1 reduced breast cancer cell migration and invasion and could partially reverse the stimulative effects of AC073352.1 overexpressed on breast cancer metastasis. Moreover, AC073352.1 might be packaged into exosomes by binding to YBX1 in breast cancer cells resulting in angiogenesis. Collectively, our results demonstrated that AC073352.1 promoted breast cancer metastasis and angiogenesis via binding YBX1, and it could serve as a promising, novel biomarker for prognosis and a therapeutic target in breast cancer.Subject terms: Breast cancer, Cell invasion, Long non-coding RNAs     

Comparisons of gene coexpression network modules in breast cancer and ovarian cancer

Background

Breast cancer and ovarian cancer are hormone driven and are known to have some predisposition genes in common such as the two well known cancer genes BRCA1 and BRCA2. The objective of this study is to compare the coexpression network modules of both cancers, so as to infer the potential cancer-related modules.

Methods

We applied the eigen-decomposition to the matrix that integrates the gene coexpression networks of both breast cancer and ovarian cancer. With hierarchical clustering of the related eigenvectors, we obtained the network modules of both cancers simultaneously. Enrichment analysis on Gene Ontology (GO), KEGG pathway, Disease Ontology (DO), and Gene Set Enrichment Analysis (GSEA) in the identified modules was performed.

Results

We identified 43 modules that are enriched by at least one of the four types of enrichments. 31, 25, and 18 modules are enriched by GO terms, KEGG pathways, and DO terms, respectively. The structure of 29 modules in both cancers is significantly different with p-values less than 0.05, of which 25 modules have larger densities in ovarian cancer. One module was found to be significantly enriched by the terms related to breast cancer from GO, KEGG and DO enrichment. One module was found to be significantly enriched by ovarian cancer related terms.

Conclusion

Breast cancer and ovarian cancer share some common properties on the module level. Integration of both cancers helps identifying the potential cancer associated modules.

     

Breast Cancer Screening Awareness,Knowledge, and Practice among Arab Women in the United Arab Emirates: A Cross-Sectional Survey

Background

Breast cancer screening can reduce morbidity and mortality and improve the survival rate for this malignancy. Low participation in screening programs has been attributable to many factors including lack of knowledge. The aim of this study was to assess breast cancer screening knowledge, attitudes and practices among women of screening age (≥40 years old) in the city of Al Ain, United Arab Emirates (UAE).

Methods

A cross-sectional survey was conducted in 2013 using the Breast Cancer Awareness Measure (CAM). Four out of twelve cultural and religious community centers in Al Ain city were randomly selected. Two hundred and forty seven women were interviewed. Chi Square test and regression analysis were used to analyze the data.

Results

Despite the increase in the uptake of screening modalities in our study group, a lack of knowledge about breast cancer screening is still evident. Almost half (44.8%) of women who never had a Clinical Breast Exam (CBE) and 44.1% of women who never had a mammography expressed a lack of knowledge about the existence of these screening techniques. Nearly one third of the participants interpreted the presence of a breast lump incorrectly and, moreover, expressed fewer worries about the nature of the lump than would normally be expected.

Conclusions

The National screening program needs to be improved and directed towards more efficient and targeted utilization of resources. Healthcare professionals play a major role in alerting women to the importance of periodic screening.     

Relationships of lipocalin 2 with breast tumorigenesis and metastasis

Breast cancer is one of the most common cancers in women worldwide and accounts for one‐sixth of cancer deaths in the United States. Breast cancer consists of a heterogeneous group of tumours classified into five types, in which the HER2/neu positive and the basal type (most are ER and HER2 negative) have the worst clinical prognosis. In recent years, prognostic/predictive markers such as ER/PR or HER2/neu have been widely used in the selection of the optimal breast cancer treatments for individual patients, which have been proven to be very effective in disease control. These results suggest that further examination of the molecular mechanisms underlying the breast tumorigenesis and identification of the potential biomarkers in different types of breast cancers will greatly benefit clinical diagnosis and facilitate the design of more effective personalized therapies to increase patient survival. This review aims to summarize recent research findings on lipocalin 2 (LCN2), a newly identified biomarker and a potential therapeutic target for breast cancer, and the possible mechanisms underlying its role in tumorigenesis and metastasis. J. Cell. Physiol. 226: 309–314, 2011. © 2010 Wiley‐Liss, Inc.     

Trends in breast cancer mortality in Trinidad and Tobago—A 35-year study

Background: Breast cancer is the most frequently diagnosed cancer among women worldwide. This study examines the breast cancer mortality patterns and trends in the Caribbean island state, Trinidad and Tobago for the 35-year period, 1970–2004. Methods: A retrospective analysis of the trends in breast cancer mortality from 1970 to 2004 was conducted. Crude mortality per 100,000 women, age-standardized mortality using World Standard population and age-stratified mortality were calculated and comparison was made between age groups above and below 50 years. Results: A general pattern of increase was observed in both crude and age-standardized mortality. The overall average crude mortality was 15.6 per 100,000 women (95% confidence interval (CI) 13.9–17.1) and the average age-standardized mortality was 18.0 per 100,000 women (95% CI 16.7–19.2). There was a pattern of increase in mortality with increasing age. The mortality rate was considerably higher for the age groups above 50 years than those less than 50 years of age both showing an upward trend over the 35-year period. Conclusions: Breast cancer mortality continued to increase over the 35-year period in Trinidad and Tobago. This study did not identify the exact reasons for this increasing trend. However, it is known that Trinidad and Tobago is becoming much more industrialized. It may be speculated that decrease in fertility rates, increase in the incidence of obesity and hormone utilization could have influenced this trend.     

USP12 promotes breast cancer angiogenesis by maintaining midkine stability

Deubiquitinases (DUBs) have important biological functions, but their roles in breast cancer metastasis are not completely clear. In this study, through screening a series of DUBs related to breast cancer distant metastasis-free survival (DMFS) in the Kaplan-Meier Plotter database, we identified ubiquitin-specific protease 12 (USP12) as a key deubiquitinating enzyme for breast cancer metastasis. We confirmed this via an orthotopic mouse lung metastasis model. We revealed that the DMFS of breast cancer patients with high USP12 was worse than that of others. Knockdown of USP12 decreased the lung metastasis ability of 4T1 cells, while USP12 overexpression increased the lung metastasis ability of these cells in vivo. Furthermore, our results showed that the supernatant from USP12-overexpressing breast cancer cells could promote angiogenesis according to human umbilical vein endothelial cell (HUVEC) migration and tube formation assays. Subsequently, we identified midkine (MDK) as one of its substrates. USP12 could directly interact with MDK, decrease its polyubiquitination and increase its protein stability in cells. Overexpression of MDK rescued the loss of angiogenesis ability mediated by knockdown of USP12 in breast cancer cells in vitro and in vivo. There was a strong positive relationship between USP12 and MDK protein expression in clinical breast cancer samples. Consistent with the pattern for USP12, high MDK expression predicted lower DMFS and overall survival (OS) in breast cancer. Collectively, our study identified that USP12 is responsible for deubiquitinating and stabilizing MDK and leads to metastasis by promoting angiogenesis. Therefore, the USP12–MDK axis could serve as a potential target for the therapeutic treatment of breast cancer metastasis.Subject terms: Breast cancer, Breast cancer     

High-density lipoprotein functionality and breast cancer: A potential therapeutic target

Breast cancer is a major cause of death globally, and particularly in developed countries. Breast cancer is influenced by cholesterol membrane content, by affecting the signaling pathways modulating cell growth, adherence, and migration. Furthermore, steroid hormones are derived from cholesterol and these play a key role in the pathogenesis of breast cancer. Although most findings have reported an inverse association between serum high-density lipoprotein (HDL)-cholesterol level and the risk of breast cancer, there have been some reports of the opposite, and the association therefore remains unclear. HDL is principally known for participating in reverse cholesterol transport and has an inverse relationship with the cardiovascular risk. HDL is heterogeneous, with particles varying in composition, size, and structure, which can be altered under different circumstances, such as inflammation, aging, and certain diseases. It has also been proposed that HDL functionality might have a bearing on the breast cancer. Owing to the potential role of cholesterol in cancer, its reduction using statins, and particularly as an adjuvant during chemotherapy may be useful in the anticancer treatment, and may also be related to the decline in cancer mortality. Reconstituted HDLs have the ability to release chemotherapeutic drugs inside the cell. As a consequence, this may be a novel way to improve therapeutic targeting for the breast cancer on the basis of detrimental impacts of oxidized HDL on cancer development.     

DNA adducts, DNA repair genotype/phenotype and cancer risk

It is well established that the initiating event in chemical carcinogenesis is the binding of reactive carcinogens to DNA. Thus, a number of analytic methods have been developed for determining levels of carcinogen-DNA adducts in humans as a marker of individual exposure and, potentially, of risk for cancer development. We have developed monoclonal and polyclonal antibodies to carcinogen-DNA adducts and highly sensitive ELISA and immunohistochemical assays for determining levels of adducts in human tissues. These methods have been combined with genotyping and phenotyping methods for DNA repair to study gene-environment interactions in cancer risk. Recent studies on breast cancer have utilized two large biorepositories. The first is blood and tumor tissues collected as part of the Long Island Breast Cancer Study Project, a population-based case-control study of environmental risk factors. The second is the Metropolitan New York Registry of Breast Cancer Families, one of six sites funded by the National Cancer Institute as a part of the Breast Cooperative Family Registry (CFR). Analysis of samples from these two studies have demonstrated the utility of measurement of DNA adducts as biomarkers of exposure and that DNA repair capacity, measured by genotyping or phenotyping, can influence risk.     

Murine model of hepatic breast cancer

Background and aimsBreast cancer is the most common cancer in women and the second leading cause of cancer-related deaths in this population. Breast cancer related deaths have declined due to screening and adjuvant therapies, yet a driving clinical need exists to better understand the cause of the deadliest aspect of breast cancer, metastatic disease. Breast cancer metastasizes to several distant organs, the liver being the third most common site. To date, very few murine models of hepatic breast cancer exist.MethodsIn this study, a novel murine model of liver breast cancer using the MDA-MB-231 cell line is introduced as an experimental (preclinical) model.ResultsHistological typing revealed consistent hepatic breast cancer tumor foci. Common features of the murine model were vascular invasion, lung metastasis and peritoneal seeding.ConclusionsThe novel murine model of hepatic breast cancer established in this study provides a tool to be used to investigate mechanisms of hepatic metastasis and to test potential therapeutic interventions.     

From Community Laywomen to Breast Health Workers: A Pilot Training Model to Implement Clinical Breast Exam Screening in Malawi

Background

Breast cancer burden is high in low-income countries. Inadequate early detection contributes to late diagnosis and increased mortality. We describe the training program for Malawi’s first clinical breast exam (CBE) screening effort.

Methods

Laywomen were recruited as Breast Health Workers (BHWs) with the help of local staff and breast cancer advocates. The four-week training consisted of lectures, online modules, role-playing, case discussions, CBE using simulators and patients, and practice presentations. Ministry of Health trainers taught health communication, promotion, and education skills. Breast cancer survivors shared their experiences. Clinicians taught breast cancer epidemiology, prevention, detection, and clinical care. Clinicians and research staff taught research ethics, informed consent, data collection, and professionalism. Breast cancer knowledge was measured using pre- and post-training surveys. Concordance between BHW and clinician CBE was assessed. Breast cancer talks by BHW were evaluated on a 5-point scale in 22 areas by 3 judges.

Results

We interviewed 12 women, and 4 were selected as BHWs including 1 breast cancer survivor. Training was dynamic with modification based on trainee response and progress. A higher-than-anticipated level of comprehension and interest led to inclusion of additional topics like breast reconstruction. Pre-training knowledge increased from 49% to 91% correct (p<0.0001). Clinician and BHW CBE had 88% concordance (kappa 0.43). The mean rating of BHW educational talks was 4.4 (standard deviation 0.7).

Conclusions

Malawian laywomen successfully completed training and demonstrated competency to conduct CBE and deliver breast cancer educational talks. Knowledge increased after training, and concordance was high between BHW and clinician CBE.     

Flubendazole induces mitochondrial dysfunction and DRP1-mediated mitophagy by targeting EVA1A in breast cancer

Breast cancer is still one of the most common malignancies worldwide and remains a major clinical challenge. We previously reported that the anthelmintic drug flubendazole induced autophagy and apoptosis via upregulation of eva-1 homolog A (EVA1A) in triple-negative breast cancer (TNBC) and was repurposed as a novel anti-tumor agent. However, the detailed underlying mechanisms remain unclear and need further investigation. Here, we found that flubendazole impairs the permeability of the mitochondrial outer membrane and mitochondrial function in breast cancer. Meanwhile, flubendazole increased dynamin-related protein (DRP1) expression, leading to the accumulation of PTEN induced putative kinase 1 (PINK1) and subsequent mitochondrial translocation of Parkin, thereby promoting excessive mitophagy. The resultant excessive mitophagy contributed to mitochondrial damage and dysfunction induced by flubendazole, thus inhibiting breast cancer cells proliferation and migration. Moreover, we demonstrated that excessive DRP1-mediated mitophagy played a critical role in response to the anti-tumor effects of EVA1A in breast cancer. Taken together, our results provide new insights into the molecular mechanisms in relation to the anti-tumor activities of flubendazole, and may be conducive to its rational use in potential clinical applications.Subject terms: Breast cancer, Pharmacology

     

Implementation of Next-Generation Sequencing in Saudi Arabia for HER2-Positive Breast Cancer

Breast cancer is a common malignancy that poses a hazard to women's health. In 2021, around 2.3 million new cases are predicted to be discovered, with a mortality rate of 6.9% on average. Breast cancer accounts for 14.8% of malignancies among the Saudis with an 8.5% fatality rate. Breast cancers that are HER2 positive account for 15 to 20% of all breast cancers. We intended to investigate the genetic mutations and the clinicopathological aspects of HER2 positive breast cancer patients. We used TruSight Tumor 15 using Next-Generation Sequencing (NGS) to look at genetic changes in 126 Saudi women with stage I to IV breast cancer. c-MET (p = 0.001), c-KIT (p = 0.001), and PIK3CA (p = 0.0001), were shown to be substantially linked with HER2 positive patients. We also detected mutations in other genes, including BRAF, EGFR, and KRAS. Tumor size, grade, stage, and nodal status were all associated with increased levels of HER2 expression. Our results recommend that patients with HER2 positive breast cancer in Saudi Arabia have a high mutational burden, which may be related to trastuzumab resistance. We expect that in the future, targeting these mutations will be a promising therapeutic method for the treatment of breast cancer.     

Clinical practice guidelines for the care and treatment of breast cancer: 14. The role of hormone replacement therapy in women with a previous diagnosis of breast cancer

Objective

To provide information and recommendations to women with a previous diagnosis of breast cancer and their physicians regarding hormone replacement therapy (HRT).

Outcomes

Control of menopausal symptoms, quality of life, prevention of osteoporosis, prevention of cardiovascular disease, risk of recurrence of breast cancer, risk of death from breast cancer.

Evidence

Systematic review of English-language literature published from January 1990 to July 2001 retrieved from MEDLINE and CANCERLIT.

Recommendations

· Routine use of HRT (either estrogen alone or estrogen plus progesterone) is not recommended for women who have had breast cancer. Randomized controlled trials are required to guide recommendations for this group of women. Women who have had breast cancer are at risk of recurrence and contralateral breast cancer. The potential effect of HRT on these outcomes in women with breast cancer has not been determined in methodologically sound studies. However, in animal and in vitro studies, the development and growth of breast cancer is known to be estrogen dependent. Given the demonstrated increased risk of breast cancer associated with HRT in women without a diagnosis of breast cancer, it is possible that the risk of recurrence and contralateral breast cancer associated with HRT in women with breast cancer could be of a similar magnitude. · Postmenopausal women with a previous diagnosis of breast cancer who request HRT should be encouraged to consider alternatives to HRT. If menopausal symptoms are particularly troublesome and do not respond to alternative approaches, a well-informed woman may choose to use HRT to control these symptoms after discussing the risks with her physician. In these circumstances, both the dose and the duration of treatment should be minimized.

Validation

Internal validation within the Steering Committee on Clinical Practice Guidelines for the Care and Treatment of Breast Cancer; no external validation.

Sponsor

The steering committee was convened by Health Canada.

Completion date

October 2001.Hormone replacement therapy (HRT) connotes treatment with either estrogen alone or estrogen with progesterone in postmenopausal women. Menopausal symptoms, such as hot flashes and vaginal dryness, and the potential long-term effects of estrogen deprivation are a concern to women with breast cancer, particularly those in whom menopause develops early as a result of adjuvant chemotherapy.Traditionally, the use of HRT has been contraindicated in women with breast cancer because of the notion that the development and growth of breast cancer is estrogen dependent and that the introduction of HRT may increase the risk of breast cancer recurrence. The focus of this guideline is on whether it is safe to give HRT to women with breast cancer.     

乳腺癌组织及肠道微生态研究进展

乳腺癌是全球女性患病率及病死率最高的恶性肿瘤,对生命健康造成极大威胁。微生物群被认为是人体“第二基因组”,在维护人类健康中扮演着重要角色,其结构及功能紊乱与疾病发生发展密切相关。随着高通量测序等生物技术的发展,诸多研究揭示了微生物群与乳腺癌关系密切,微生物群可能通过影响雌激素代谢、干预细胞增殖与凋亡、调节免疫及炎症等途径影响乳腺癌的发生发展,并可能影响乳腺癌对化疗及免疫治疗的反应。本文就乳腺癌组织微生态与肠道微生态研究概况展开综述,并提出预防和治疗乳腺癌的新策略。

     

Discovery of pathway biomarkers from coupled proteomics and systems biology methods

Background

Breast cancer is worldwide the second most common type of cancer after lung cancer. Plasma proteome profiling may have a higher chance to identify protein changes between plasma samples such as normal and breast cancer tissues. Breast cancer cell lines have long been used by researches as model system for identifying protein biomarkers. A comparison of the set of proteins which change in plasma with previously published findings from proteomic analysis of human breast cancer cell lines may identify with a higher confidence a subset of candidate protein biomarker.

Results

In this study, we analyzed a liquid chromatography (LC) coupled tandem mass spectrometry (MS/MS) proteomics dataset from plasma samples of 40 healthy women and 40 women diagnosed with breast cancer. Using a two-sample t-statistics and permutation procedure, we identified 254 statistically significant, differentially expressed proteins, among which 208 are over-expressed and 46 are under-expressed in breast cancer plasma. We validated this result against previously published proteomic results of human breast cancer cell lines and signaling pathways to derive 25 candidate protein biomarkers in a panel. Using the pathway analysis, we observed that the 25 “activated” plasma proteins were present in several cancer pathways, including ‘Complement and coagulation cascades’, ‘Regulation of actin cytoskeleton’, and ‘Focal adhesion’, and match well with previously reported studies. Additional gene ontology analysis of the 25 proteins also showed that cellular metabolic process and response to external stimulus (especially proteolysis and acute inflammatory response) were enriched functional annotations of the proteins identified in the breast cancer plasma samples. By cross-validation using two additional proteomics studies, we obtained 86% and 83% similarities in pathway-protein matrix between the first study and the two testing studies, which is much better than the similarity we measured with proteins.

Conclusions

We presented a ‘systems biology’ method to identify, characterize, analyze and validate panel biomarkers in breast cancer proteomics data, which includes 1) t statistics and permutation process, 2) network, pathway and function annotation analysis, and 3) cross-validation of multiple studies. Our results showed that the systems biology approach is essential to the understanding molecular mechanisms of panel protein biomarkers.

     

YTHDF1 promotes breast cancer cell growth,DNA damage repair and chemoresistance

Chemoresistance represents a major obstacle to the treatment of human cancers. Increased DNA repair capacity is one of the important mechanisms underlying chemoresistance. In silico analysis indicated that YTHDF1, an m6A binding protein, is a putative tumor promoter in breast cancer. Loss of function studies further showed that YTHDF1 promotes breast cancer cell growth in vitro and in vivo. YTHDF1 facilitates S-phase entry, DNA replication and DNA damage repair, and accordingly YTHDF1 knockdown sensitizes breast cancer cells to Adriamycin and Cisplatin as well as Olaparib, a PARP inhibitor. E2F8 is a target molecule by YTHDF1 which modulates E2F8 mRNA stability and DNA damage repair in a METTL14-dependent manner. These data demonstrate that YTHDF1 has a tumor-promoting role in breast cancer, and is a novel target to overcome chemoresistance.Subject terms: Breast cancer, Breast cancer