Using Breast Cancer Risk Associated Polymorphisms to Identify Women for Breast Cancer Chemoprevention

Ziv, Elad; Tice, Jeffrey A.; Sprague, Brian L.; Vachon, Celine M.; Cummings, Steven R.; Kerlikowske, Karla

doi:10.1371/journal.pone.0168601

Cited by 16 publications

(13 citation statements)

References 43 publications

(48 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This variation reflects different motives in decision makers (representing reduction or increase in screening efforts on average). Based on the literature, we chose four different thresholds of relative risks (RR) of 2, 1.5, 1, and 0.5 [28, 29] to create five combinations of high-, medium-, and low-risk groups:…”

Section: Methodsmentioning

confidence: 99%

Is risk-stratified breast cancer screening economically efficient in Germany?

2019

View full text Add to dashboard Cite

Objectives Risk stratification has so far been evaluated under the assumption that women fully adhere to screening recommendations. However, the participation in German cancer screening programs remains low at 54%. The question arises whether risk-stratified screening is economically efficient under the assumption that adherence is not perfect. Method We have adapted a micro-simulation Markov model to the German context. Annual, biennial, and triennial routine screening are compared with five risk-adapted strategies using thresholds of relative risk to stratify screening frequencies. We used three outcome variables (mortality reduction, quality-adjusted life years, and false-positive results) under the assumption of full adherence vs. an adherence rate of 54%. Strategies are evaluated using efficiency frontiers and probabilistic sensitivity analysis (PSA). Results The reduced adherence rate affects both performance and cost; incremental cost-effectiveness ratios remain constant. The results of PSA show that risk-stratified screening strategies are more efficient than biennial routine screening under certain conditions. At any willingness-to-pay (WTP), there is a risk-stratified alternative with a higher likelihood of being the best choice. However, without explicit decision criteria and WTP, risk-stratified screening is not more efficient than biennial routine screening. Potential improvements in the adherence rates have significant health gains and budgetary implications. Conclusion If the participation rate for mammographic screening is as low as in Germany, stratified screening is not clearly more efficient than routine screening but dependent on the WTP. A more promising design for future stratified strategies is the combination of risk stratification mechanisms with interventions to improve the low adherence in selected high-risk groups.

show abstract

Section: Methodsmentioning

confidence: 99%

Is risk-stratified breast cancer screening economically efficient in Germany?

2019

View full text Add to dashboard Cite

show abstract

“…This finding might be of relevance with regard to breast cancer chemoprevention, which aims to reduce disease incidence by the administration of anti-estrogen drugs such as selective estrogen receptor modifiers (e.g., tamoxifen) (83). The selection of women who could most benefit from these risk reducing medications might be improved by genetic testing based on polymorphisms that affect breast cancer risk (84).…”

Section: Discussionmentioning

confidence: 97%

Breast cancer susceptibility: an integrative analysis of genomic data

Mocellin

Valpione

Róssi

et al. 2018

Preprint

View full text Add to dashboard Cite

BackgroundGenome wide association studies (GWAS) are greatly accelerating the pace of discovery of germline variants underlying the genetic architecture of sporadic breast cancer predisposition. We have built the first knowledge-base dedicated to this field and used it to generate hypotheses on the molecular pathways involved in disease susceptibility. MethodsWe gathered data on the common single nucleotide polymorphisms (SNPs) discovered by breast cancer risk GWAS. Information on SNP functional effect (including data on linkage disequilibrium, expression quantitative trait locus, and SNP relationship with regulatory motifs or promoter/enhancer histone marks) was utilized to select putative breast cancer predisposition genes (BCPGs). Ultimately, BCPGs were subject to pathway (gene set enrichment) analysis and network (protein-protein interaction) analysis. ResultsData from 38 studies (28 original case-control GWAS enrolling 383,260 patients with breast cancer; and 10 GWAS meta-analyses) were retrieved. Overall, 281 SNPs were associated with the risk of breast cancer with a P-value <10E-06 and a minor allele frequency >1%. Based on functional information, we identified 296 putative BCPGs. Primary analysis showed that germline perturbation of classical cancer-related pathways (e.g., apoptosis, cell cycle, signal transduction including estrogen receptor signaling) play a significant role in breast carcinogenesis. Other less established pathways (such as ribosome and peroxisome machineries) were also highlighted. In the main subgroup analysis, we considered the BCPGs encoding transcription factors 4 (n=36), which in turn target 252 genes. Interestingly, pathway and network analysis of these genes yielded results resembling those of primary analyses, suggesting that most of the effect of genetic variation on disease risk hinges upon transcriptional regulons. ConclusionsThis knowledge-base, which is freely available and will be annually updated, can inform future studies dedicated to breast cancer molecular epidemiology as well as genetic susceptibility and development.

show abstract

“…Polymorphisms of single nucleotides or of larger DNA fragments and all the other abovementioned pathways are widely associated with the development of cancer in general. Aberrant activation of these pathways in breast cancer is part of the oncogenic mechanisms contributing to disease progression and is the focus of many current studies, since the disruption of mechanisms affected by these pathways may lead to pathogenic events (Mocellin, Valpione, Rossri, & Pooley, 2018;Nicolini, 2017.;Ziv et al, 2017). The description of these changes is very relevant from the point of view of genetic susceptibility.…”

Section: Discussionmentioning

confidence: 99%

Copy number alterations associated with clinical features in an underrepresented population with breast cancer

Peres

Carvalho

Anurag

et al. 2019

Molec Gen & Gen Med

View full text Add to dashboard Cite

Background As the most incident tumor among women worldwide, breast cancer is a heterogeneous disease. Tremendous efforts have been made to understand how tumor characteristics as histological type, molecular subtype, and tumor microenvironment collectively influence disease diagnosis to treatment, which impact outcomes. Differences between populations and environmental and cultural factors have impacts on the origin and evolution of the disease, as well as the therapeutic challenges that arise due to these factors. We, then, compared copy number variations (CNVs) in mucinous and nonmucinous luminal breast tumors from a Brazilian cohort to investigate major CNV imbalances in mucinous tumors versus non‐mucinous luminal tumors, taking into account their clinical and pathological features. Methods 48 breast tumor samples and 48 matched control blood samples from Brazilian women were assessed for CNVs by chromosome microarray. Logistic regression and random forest models were used in order to assess CNVs in chromosomal regions from tumors. Results CNVs that were identified in chromosomes 1, 5, 8, 17, 19, and 21 classify tumors according to their histological type, ethnicity, disease stage, and familial history. Conclusion Copy number alterations described in this study provide a better understanding of the landscape of genomic aberrations in mucinous breast cancers that are associated with clinical features.

show abstract

Using Breast Cancer Risk Associated Polymorphisms to Identify Women for Breast Cancer Chemoprevention

Cited by 16 publications

References 43 publications

Is risk-stratified breast cancer screening economically efficient in Germany?

Is risk-stratified breast cancer screening economically efficient in Germany?

Breast cancer susceptibility: an integrative analysis of genomic data

Copy number alterations associated with clinical features in an underrepresented population with breast cancer

Contact Info

Product

Resources

About