Breast Cancer Risk Research Articles

1558P Independent validation of the Breast Cancer Risk Assessment Tool (Gail model) for predicting breast cancer risk in Egyptian population

1558P Independent validation of the Breast Cancer Risk Assessment Tool (Gail model) for predicting breast cancer risk in Egyptian population

207P Associations of diabetic background retinopathy and ER+ breast cancer risk: A Mendelian randomization study

207P Associations of diabetic background retinopathy and ER+ breast cancer risk: A Mendelian randomization study

Night shift work and breast cancer risk – 2023 update of epidemiologic evidence

IntroductionNight shift work is a complex and frequent occupational exposure, and breast cancer stands as the most prevalent cancer in women. The International Agency for Research on Cancer (IARC) has twice classified night shift work as a probable breast carcinogen, with the latest classification in June 2019. Since that time, new epidemiologic data has emerged. MethodsWe searched PubMed for original articles based on cohort and case- control studies of “breast cancer and night shift work” published after the IARC evaluation in June 2019. ResultsIn total six cohorts and four case-control studies were included in our review. Overall, we observed some support for associations between persistent (long duration or high frequency) night shift work and an increase in breast cancer risk, though most studies were relatively small and statistically under-powered. Moreover, the recent studies do not contribute further evidence regarding the interaction with menopausal status, diurnal preference, hormonal subtypes of breast cancer or gene-environment aspects, which were issues that were left from the IARC evaluation. ConclusionThe available new results somewhat consolidate the epidemiological evidence from IARC's 2019 evaluation, and do not provide further evidence regarding interaction of interest, e.g. menopausal status, etc. Therefore, long term follow-up of prospective cohorts or nested case-control studies, including precise exposure assessment and examinations of relevant interactions such as menopausal status, diurnal preference, hormonal subtypes of breast cancer and gene-environment aspects, are warranted. Meanwhile, protective measures for the night workers should be considered.

A cause-effect relationship between uterine diseases and breast cancer: A bidirectional Mendelian randomization study

ObjectiveTo explore the cause-effect relationship between uterine diseases (UDs) and breast cancer (BC) and underlying mechanism of the cause-effect relationship, enhance understanding of the association between BC and UDs. MethodsA two-sample bidirectional Mendelian randomization (MR) analysis was conducted. We obtained summary statistics data from GWAS for BC, endometriosis, endometrial cancer (EC), uterine leiomyoma (UL), uterine polyps (UP), and cervical cancer (CC). Independent SNPs were selected as instrumental variables (IVs) for each disease. The inverse variance weighted (IVW) method was primary used for estimating the causal association between UDs and BC. To further evaluate the consistency and dependability of the results, we also utilized the weighted median, weighted mode, simple mode, and MR-Egger methods, along with sensitivity analyses. Furthermore, a supplementary analysis focusing on the variants linked to BC and UDs was conducted. This involved identifying corresponding genes and subsequently performing KEGG/GO analyses to investigate potential molecular mechanisms. ResultsThe results indicated significant associations between genetic susceptibility to endometriosis, EC, and UL with BC risk. The odds ratios (ORs) were as follows: endometriosis at 0.963 (95 % CI, 0.942–0.984; p = 7.11e-5), EC at 1.056 (95 % CI, 1.033–1.081; p = 2.39e-6), and UL at 1.027 (95 % CI, 1.006–1.048; p = 0.010). Conversely, the predisposition to BC inferred from genetic factors was markedly correlated with an elevated risk of EC indicated by an OR of 1.066 (95 % CI, 1.019–1.116; p = 0.006), and was correlated with UP risk (OR, 1.001,95 % CI, 1.000–1.002; p = 0.001).Sensitivity analyses provided weak evidence for these effects, suggesting that the study's outcomes are consistent and trustworthy. Further analysis of the genetic variants associated with BC, and these related genes are enriched in Cellular senescence, GnRH secretion, Phosphatidylinositol signaling system, and so on. ConclusionThis study corroborates the existence of a reciprocal causal relationship between BC and EC, as well as highlighting the substantial correlations between a genetic susceptibility to UL and endometriosis with BC. BC may exert their influence on EC and UP through Cellular senescence, GnRH secretion, and other pathways. These discoveries offer fresh perspectives on the genetic pathogenesis of BC and UDs, and can guide future experimental studies. Additionally, they lay down a groundwork for the development of tailored preventative and therapeutic strategies moving forward.

380P Assessing interstitial lung disease (ILD) risk in metastatic breast cancer (MBC): A comprehensive meta and network analysis of antibody-drug conjugates (ADCs) compared to available treatment options beyond first-line (1L)

380P Assessing interstitial lung disease (ILD) risk in metastatic breast cancer (MBC): A comprehensive meta and network analysis of antibody-drug conjugates (ADCs) compared to available treatment options beyond first-line (1L)

IKNOW—Supporting the counseling of women with hereditary risk of breast and ovarian cancer with digital technologies: A randomized controlled trial

PurposeWe developed the online-based counseling tool iKNOW for women with a pathogenic germline variant in BRCA1/2 to improve risk understanding and quality of life. MethodsWith a randomized controlled trial, we investigated the efficacy of iKNOW with regard to risk understanding (primary endpoint), quality of life, risk perception, and anxiety (secondary endpoints). Self-report questionnaires were administered to N = 217 women with a pathogenic variant in BRCA1/2 before counseling (T0), immediately after (T1), 4 weeks after (T2), and 6 months after (T3). ResultDeviations between self-assessed and calculated cancer risks tended to be smaller in the intervention group than in the control group but no longer significantly after adjustment for multiple testing. In the intervention group, the proportion of women with a correct understanding of breast cancer risk at T3 was higher (30.7% vs 14.7%; P = .032). There were no differences in secondary endpoints. ConclusioniKNOW tends to positively influence the understanding of familial cancer risk. At the same time, it does not negatively influence any of the secondary endpoints. However, converging evidence suggests that iKNOW seems to affect the quality of counseling processes and can thus be used as a paradigm for reinventing the notion of efficient, digital care.

Association between Inflammatory Dietary Pattern and Mammographic Features

BackgroundThe empirical dietary inflammation pattern score (EDIP), which measures the ability of the diet to regulate chronic inflammation, is associated with both higher adiposity and breast cancer (BC) risk. Mammographic density (MD) is an important risk factor for BC. ObjectiveWe examined the associations between EDIP and mammographic features overall and stratified by menopausal status, and assessed the extent to which these associations are mediated by adiposity. MethodsWe included 4145 participants without BC in the Nurses’ Health Study (NHS) and NHSII. Cumulative average EDIP was assessed by food frequency questionnaires every 4–6 y. We assessed MD parameters (percent MD, dense area, and nondense area) and V (measure of grayscale variation). MD parameters were square-root transformed. Multivariable-adjusted linear regression models were used to analyze the associations between EDIP score and MD parameters. Baron and Kenny’s regression method was used to assess the extent to which the associations of EDIP and mammographic traits were mediated by BMI. ResultsIn multivariable-adjusted models, EDIP was significantly inversely associated with percent MD [top compared with bottom quartile, β = –0.57; 95% confidence interval (CI): –0.78, –0.36]. Additional adjustment for BMI attenuated the association (β = –0.15; 95% CI: –0.34, 0.03), with 68% (β = 0.68, 20; 95% CI: 0.54, 0.86) mediation via BMI. In addition, EDIP was positively associated with nondense area after adjusting for BMI and other covariates. No associations were observed for dense area and V measure. Results were similar when stratified by menopausal status. ConclusionsEDIP score was inversely associated with percent MD and positively associated with nondense area, and these associations were largely mediated by BMI.

The association between infectious agents and breast cancer: a review of the epidemiologic evidence.

Several viruses have been casually linked to human cancers, including cervical, nasopharyngeal, liver, sarcoma, and Merkel cell carcinomas. However, the etiologic contribution of viral infections to breast cancer, the number one incident cancer among women worldwide, is not well established. Among studies exploring associations of viruses with breast cancer, potential linkages have been identified between breast cancer and five viruses: beta retrovirus, (i.e., mouse mammary tumor virus), human papillomavirus, Epstein Barr virus. bovine leukemia virus, and human cytomegalovirus. In this review, we provide a comprehensive evaluation of epidemiological ecologic, case-control, case-only, and cohort studies investigating these associations. Wediscuss results from several existing reviews and meta-analyses, evaluate epidemiological studies published in the past five years, and assess the relationship between these viruses and breast tumor clinicopathological factors. The strongest epidemiological evidence for a viral role in breast cancer exists for MMTV and HPV, though limitations include lack of prospective studies for MMTV and potential detection bias in HPV studies. Viral detection challenges have limited studies of EBV and HCMV. Fewer studies have evaluated BLV, and though it has been associated with higher risk of breast cancer, sample sizes are quite small. CONCLUSION: While epidemiologic evidence exists for an association between these five viruses and breast cancer, various methodological issues and lack of prospective studies preclude robustconclusions. Future research should prioritize establishing a temporal relationship between infection and disease, minimizing misclassification of detection assays, and further exploring the influence of co-infections.

Overcoming challenges in conducting early phase breast cancer prevention trials: Bazedoxifene and conjugated estrogens vs waitlist control

BackgroundThe combination of bazedoxifene 20 mg (BZA) and conjugated estrogens 0.45 mg (CE) marketed as Duavee® is approved for vasomotor symptom relief and osteoporosis prevention. Our pilot study suggested it had potential breast cancer risk reduction, and we proposed a multisite Phase IIB primary prevention trial assessing change in breast imaging and tissue risk biomarkers. By the time funding was acquired in February 2021, Duavee® was unavailable with an uncertain return date. A redesign was needed to salvage the study. MethodsThe basic trial design was minimally altered. Women age 45–64 at elevated risk for breast cancer with vasomotor symptoms and no menses for at least 2 months have mammography, phlebotomy, and benign breast tissue sampling before and after 6 months of intervention. However, instead of Duavee® (single pill) vs placebo, women are randomized to 6 months of BZA + CE vs Waitlist. Those initially randomized to Waitlist can receive BZA + CE after 6 months. The primary endpoint is between arm difference in change in a fully automated measure of mammographic density with blood and tissue-based secondary endpoints. OutcomesAccrual initiation was delayed due to contractual difficulties surrounding BZA importation during COVID-19 and deploying a fully automated method (Volpara®) to assess the primary endpoint. To accommodate this delay, a mid-grant no cost extension along with amended eligibility requirements were employed. 61/120 participants needed were entered in the initial 27 months of accrual and 37 months of funding. Despite a late start, accrual is likely to be completed within the funding period.

Genetic Analysis Uncovers Potential Mechanisms Linking Juvenile ldiopathic Arthritisto Breast Cancer: A BioinformaticPilot Study

BackgroundIn recent years, concerns have emerged regarding the potential link between Juvenile idiopathic arthritis (JIA) and an elevated risk of developing breast cancer. However, the potential relationship between JIA and breast cancer is currently unclear. The objective of this study is to investigate the mechanism of JIA on cancer risk. MethodsUse the Bulk-seq data related to JIA, selected from the GEO database, to explore potential candidate genes using methods such as WGCNA and consensus machine learning labeling. Verify using breast cancer Bulk-seq data from TCGA and scRNA-seq analyses. ResultsA total of 2050 genes potentially related to JIA were identified by WGCNA, and after merged with differentially expressed genes, 43 potential candidate genes were finding. Subsequently, consensus machine learning label analysis was conducted on the aforementioned genes, and a total of 6 genes closely related to JIA were identified. Subsequently, in breast cancer, we found that PRRG4, NCR3 and CREB5 also had significant differences in TCGA. And it is closely related to prognosis. ScRNA-seq analysis showed that the expression of PRRG4 was different in T cells in JIA, and PRRG4 was mainly expressed in T cells in breast cancer. ConclusionsThe findings of this study support a mechanism between JIA and an increased risk of breast cancer.

Background parenchymal enhancement on contrast-enhanced mammography: associations with breast density and patient's characteristics.

To evaluate if background parenchymal enhancement (BPE) on contrast-enhanced mammography (CEM), graded according to the2022 CEM-dedicated Breast Imaging Reporting and Data System (BI-RADS) lexicon, is associated with breast density, menopausal status, and age. This bicentric retrospective analysis included CEM examinations performed for thework-up of suspicious mammographic findings. Three readers independently and blindly evaluated BPE on recombined CEM images and breast density on low-energy CEM images. Inter-reader reliability was estimated using Fleiss κ. Multivariable binary logistic regression was performed, dichotomising breast density and BPE as low (a/b BI-RADS categories, minimal/mild BPE) and high (c/d BI-RADS categories, moderate/marked BPE). A total of 200 women (median age 56.8years, interquartile range 50.5-65.6, 140/200 in menopause) were included. Breast density was classified as a in 27/200 patients (13.5%), as b in 110/200 (55.0%), as c in 52/200 (26.0%), and as d in 11/200 (5.5%), with moderate inter-reader reliability (κ = 0.536; 95% confidence interval [CI] 0.482-0.590). BPE was minimal in 95/200 patients (47.5%), mild in 64/200 (32.0%), moderate in 25/200 (12.5%), marked in 16/200 (8.0%), with substantial inter-reader reliability (κ = 0.634; 95% CI 0.581-0.686). At multivariable logistic regression, premenopausal status and breast density were significant positive predictors of high BPE, with adjusted odds ratios of 6.120 (95% CI 1.847-20.281, p = 0.003) and 2.416 (95% CI 1.095-5.332, p = 0.029) respectively. BPE on CEM is associated with well-established breast cancer risk factors, being higher in women with higher breast density and premenopausal status.

83P Circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) in eary high risk breast cancer: The CITUCEL trial update

83P Circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) in eary high risk breast cancer: The CITUCEL trial update

Exploring pathogenic SNPs and estrogen receptor alpha interactions in breast cancer: An in silico approach

The estrogen receptor 1 gene (ESR1) plays a crucial role in breast and mammary development in humans. Alterations such as gene amplification, genomic rearrangements, and missense mutations in the ESR1 gene are reported to increase the risk of breast cancer in humans. The purpose of this study is to analyze the missense mutations and molecular modeling of ESR1, focusing on the pathogenic SNP H516N, for a better understanding of disease risk and future benefits for therapeutic benefits. This SNP was selected based on its location in the binding pocket of ESR1 and its predicted impact on drug binding. The in silico analysis was performed by applying various computational approaches to identify highly pathogenic SNPs in the binding pocket of ESR1. The effect of the SNP was explored through docking and intra-molecular interaction studies. All SNPs in ESR1 were identified followed by the identification of the highly pathogenic variant located in the binding pocket of ESR1. The mutant model of the pathogenic SNP H516N was generated, and hydroxytamoxifen was docked with the wild-type and the mutant model. The mutant model lost the formation of stable hydrogen bonds with the active site residues and hydroxytamoxifen, which may result in reduced binding affinity and therefore, will predict the patient's response to estrogenic inhibitors.

Genetic evidence supporting potential causal roles of EIF4 family in breast cancer: a two-sample randomized Mendelian study

Translational control plays a crucial role in the regulation of apoptosis, with the EIF4 family serving as one of the mRNA translation factors that modulate the process of mRNA translation based on mRNA characteristics. To address this potential causal role of EIF4 family proteins and breast cancer, Mendelian randomization was employed. The study incorporated four sets of genetics instrumental variables, namely EIF4E, EIF4B, EIF4A, and EIF4EBP2. The outcome variables selected for analysis were the BCAC consortium, which included estrogen receptor positive (ER+) and estrogen receptor negative (ER−) samples. To assess the potential violations of the MR assumption, the primary MR analysis employed inverse variance weighted (IVW), and several sensitivity analyses were conducted. The findings of the two-sample MR analysis indicate that EIF4E has an adverse effect on breast cancer risk (p = 0.028). However, the evidence for the relationship between EIF4E and ER status of breast cancer suggests a weak association with ER+ breast cancer (p = 0.054), but not with ER- breast cancer (p > 0.05). The study findings indicate that EIF4A is not causally linked to the risk of ER+ breast cancer, but is significantly associated with an elevated risk of ER− breast cancer (p = 0.028). However, the evidence is inadequate to support the effects of EIF4B and EIF4EBP2 on breast cancer (p > 0.05). Our results suggest that EIF4 may be a potential factor in the occurrence and development of breast cancer, which may lead to a better understanding of its causes and prevention.

Investigating the effect of resveratrol on the survival rate of 4T1 breast cancer cells by MTT method

Cancer is known as an incurable, deadly and deadly disease with pain and disability. During recent decades, changes in people's lifestyles have increased the incidence and prevalence of breast cancer worldwide. With the wide spread of this disease, research has also increased on this issue. Resveratrol is known as a natural polyphenol found in red grapes and some other foods, and with its important anti-cancer properties, it can be effective in reducing the risk of breast cancer and its treatment. Research has shown that resveratrol can have positive effects on breast cancer by reducing DNA methylation, reducing cell proliferation, and reducing cancer growth factors. In this research, resveratrol has been used against 4T1 cancer cells, which were treated with different concentrations of resveratrol after cultivation in 96-well plates and measured by the MTT method. The obtained results showed that resveratrol in all concentrations and at different times significantly reduces the survival of 4T1 cancer cells. By increasing the concentration and treatment time, the decrease in cell viability increases. This indicates strong, dose- and time-dependent effects of resveratrol on breast cancer cells.

ASO Visual Abstract: The Impact of a Breast Cancer Risk Assessment on the Decision for Gender-Affirming Chest Masculinization Surgery in Transgender and Gender-Diverse Individuals-A Pilot Single-Arm Educational Intervention Trial.

ASO Visual Abstract: The Impact of a Breast Cancer Risk Assessment on the Decision for Gender-Affirming Chest Masculinization Surgery in Transgender and Gender-Diverse Individuals-A Pilot Single-Arm Educational Intervention Trial.

The Association Between Physical Activity and risk for breast cancer in US female adults: A cross-sectional study based on NHANES 2011–2020

BackgroundBreast cancer poses a significant threat to women's health worldwide. This study aimed to evaluate the association between various levels of physical activity and the incidence of breast cancer. MethodsThe data for this study were obtained from the National Health and Nutrition Examination Survey (NHANES), spanning 2011 to 2020. The study included female participants aged 20 years or older, who provided detailed data on breast cancer incidence, physical activity levels, and other pertinent variables. Adjusted odds ratios (ORs) and 95 % confidence intervals (CIs) were calculated using multivariate logistic regression analyses, alongside subgroup and sensitivity analyses. ResultsAfter adjusting for potential confounders, multivariate logistic regression analyses indicated that compared to individuals with low physical activity (<600 METs min/week), light physical activity (600 to < 1800 METs min/week), moderate physical activity (1800 to < 3000 METs min/week) and high physical activity (≥3000 METs min/week) were associated with breast cancer with adjusted ORs of 0.95 (95 % CI 0.68–1.34, P = 0.787), 0.92 (95 % CI 0.57–1.49, P = 0.747), and 0.56 (95 % CI 0.37–0.86, P = 0.009) respectively. These results were consistent across sensitivity and subgroup analyses. ConclusionHigh-intensity physical activity may decrease the risk of breast cancer, highlighting the importance of proactively implementing healthy lifestyle interventions to protect the health of adult women.

Colocalised Genetic Associations Reveal Alternative Splicing Variants as Candidate Causal Links for Breast Cancer Risk in 10 Loci.

Genome-wide association studies (GWASs) have revealed numerous loci associated with breast cancer risk, yet the precise causal variants, their impact on molecular mechanisms, and the affected genes often remain elusive. We hypothesised that specific variants exert their influence by affecting cis-regulatory alternative splice elements. An analysis of splicing quantitative trait loci (sQTL) in healthy breast tissue from female individuals identified multiple variants linked to alterations in splicing ratios. Through colocalisation analysis, we pinpointed 43 variants within twelve genes that serve as candidate causal links between sQTL and GWAS findings. In silico splice analysis highlighted a potential mechanism for three genes-FDPS, SGCE, and MRPL11-where variants in proximity to or on the splice site modulate usage, resulting in alternative splice transcripts. Further in vitro/vivo studies are imperative to fully understand how these identified changes contribute to breast oncogenesis. Moreover, investigating their potential as biomarkers for breast cancer risk could enhance screening strategies and early detection methods for breast cancer.

Protein-truncating and rare missense variants in ATM and CHEK2 and associations with cancer in UK Biobank whole-exome sequence data

BackgroundDeleterious germline variants in ATM and CHEK2 have been associated with a moderately increased risk of breast cancer. Risks for other cancers remain unclear.MethodsCancer associations for coding variants in ATM...

The genetic variants of miR-1206 and miR-125b in breast cancer patients: in vitro and in silico analysis

Background This study aimed to investigate the association of rs12976445 polymorphism in the promoter region of miR-125a and rs2114358 in the precursor region of miR-1206 to breast cancer susceptibility. Method A total of 230 participants (110 breast cancer and 120 controls) enrolled in this study and extracted genomic DNA. The genotypes were determined by the Tetra-ARMS method. The allele and genotype frequencies were determined. Results Allele variation in the rs12976445 (miR-125a) sequence increased the risk of breast cancer; a significant relationship was observed between breast cancer and allele change in individuals with the C allele (p = 0.01). However, allele variation in the rs2114358 (miR-1206) decreased the risk of breast cancer in individuals with allele A (p = 0.01). In silico study showed that allele change was associated with a reduction in structural stability. Conclusion Therefore, the rs12976445 variant can be considered a risk factor for breast cancer, and the rs2114358 variant is a protective factor against it.