Breast Cancer Research最新文献

{"title":"Pharmacological CLK inhibition disrupts SR protein function and RNA splicing blocking cell growth and migration in TNBC.","authors":"Nasi Liu, Jurjun J S van der Velde, Sherien Ramdjielal, Esmee Koedoot, Nila K van Overbeek, Daisy Batenburg, Alfred C O Vertegaal, Bob van de Water, Sylvia E Le Dévédec","doi":"10.1186/s13058-025-02091-w","DOIUrl":"https://doi.org/10.1186/s13058-025-02091-w","url":null,"abstract":"<p><strong>Background: </strong>Dysregulation of alternative splicing plays a pivotal role in tumorigenesis and metastasis in triple-negative breast cancer (TNBC). Serine/arginine-rich (SR) proteins, essential components of the spliceosome, undergo phosphorylation by Cdc2-like kinase (CLK). Here we explored the impact of pharmacological inhibition of CLK using a novel inhibitor, T-025, on the spliceosome complex and transcriptional responses in relation to cell proliferation and migration in TNBC.</p><p><strong>Methods: </strong>We evaluated the anti-proliferative and anti-migratory efficacy of T-025 in a spectrum of TNBC cell lines. Fluorescent reporter cell lines and flowcytometry were used to determine the effect of T-025 on cell cycle. Deep RNA sequencing was performed to unravel the differentially expressed genes (DEGs) and alternatively spliced genes (ASGs) upon T-025 treatment. Pulldown/MS was used to uncover the impact of T-025 on SRSF7 interactome. Live-cell imaging and photobleaching experiments were conducted to determine the subnuclear localization of SRSF7-GFP and its dynamic mobility.</p><p><strong>Results: </strong>T-025 exhibited a potent anti-proliferative effect in a spectrum of TNBC cell lines, particularly in highly proliferative cell lines. Treatment with T-025 induced cell cycle arrest in the G1-S phase, resulting in an increased proportion of aneuploidy cells and cells with 4 N DNA. T-025 significantly inhibited cell migration in highly migratory TNBC cell lines. Deep RNA sequencing uncovered numerous DEGs and ASGs upon T-025 treatment, which were significantly enriched in pathways related to cell division, RNA splicing and cell migration. Pulldown/MS showed that SRSF7 interacted more with nuclear-speckle-residing proteins, while less with RNA helicases and polymerases upon T-025 treatment. Enhanced interactions between SRSF7 and other phosphorylated SR proteins localized at nuclear speckles were also observed. Live-cell imaging indicated that T-025 treatment induced the accumulation of SRSF7-GFP at nuclear speckles and nuclear speckles' enlargement, restricting its protein dynamic mobility.</p><p><strong>Conclusions: </strong>CLK inhibition using T-025 leads to the accumulation of splicing factors at nuclear speckles and stalls their release to splicing sites, resulting in the RNA splicing reprogramming of a large number of genes involved in cell division, migration and RNA splicing. Our findings provide evidence that T-025 could be a promising therapeutic drug for TNBC patients.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"27 1","pages":"140"},"PeriodicalIF":5.6,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144745582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Missense variants in PRKCD: elucidating their potential association with breast cancer.","authors":"Sameen Zafar, Yasmin Badshah, Maria Shabbir, Uzma Mussarat, Asma Latif, Janeen H Trembley, Tayyaba Afsar, Fohad Mabood Husain, Suhail Razak","doi":"10.1186/s13058-025-02090-x","DOIUrl":"10.1186/s13058-025-02090-x","url":null,"abstract":"<p><strong>Background: </strong>Missense single-nucleotide polymorphisms (SNPs) in various genetic pathways can lead to the development of breast cancer. Protein kinase C delta (PRKCD) is involved in various important cellular pathways, and its altered expression has been identified in different cancers. Genetic alteration in this gene can be involved in cancer onset and progression. To date, there are no studies performed to elucidate the role of PRKCD missense variants in the development of breast cancer. Therefore, this study aims to identify the association of pathogenic missense SNPs in PRKCD with breast cancer.</p><p><strong>Methods: </strong>The missense variants of PRKCD were retrieved from the Ensembl and dbSNP databases. Missense variants were analysed through various computational tools, and four variants of PRKCD rs1703806197 (T/C), rs782555227 (G/A), rs1703449438 (T/C), and rs1575535582 (T/G) were selected from the data. The genotype analysis for these variants was performed for 360 breast cancer patients and 363 healthy controls. Statistical association of variants with breast cancer clinical features was determined through chi-square/Fisher's exact test with a significant P value ≤ 0.05 using GraphPad Prism 8.0 software.</p><p><strong>Results: </strong>Genotype analysis of PRKCD variants showed that missense SNPs rs782555227 (G/A), rs1703449438 (T/C), and rs1575535582 (T/G) were associated with breast cancer (P value < 0.05). Furthermore, genotypes in these SNPs were also found to be associated with various clinical features of breast cancer patients. Genotypes AG, TC, and TT in variants rs782555227, rs1703449438, and rs1575535582, respectively, were associated with breast cancer metastasis. While genotype AG of variant rs782555227 was also found to be associated with menopausal status and hereditary breast cancer. Moreover, genotype TT in variant rs1575535582 was associated with BRCA1 positive status among the breast cancer patients.</p><p><strong>Conclusion: </strong>The present study identified for the first time the association of specific PRKCD missense variants with breast cancer. These variants could be developed into possible genetic markers for the diagnosis of breast cancer at an early stage; however, further validation studies with a multiethnic large cohort size are required. Furthermore, functional studies of these variants will also aid in attaining insight into the molecular mechanisms through which these missense variants are involved in breast cancer.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"27 1","pages":"139"},"PeriodicalIF":5.6,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12305980/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144734895","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Short-term consumption of the modified standard American diet perturbed the metabolic balance and altered DNA damage in MMTV-PyMT transgenic mice.","authors":"Arlet Hernandez, Alekhya Puppala, Jenna Hedlich-Dwyer, Nayonika Mukherjee, Guihua Zhai, Valeria L Dal Zotto, Bohan Ning, Hua Guo, Ritu Aneja, Natalie R Gassman","doi":"10.1186/s13058-025-02075-w","DOIUrl":"10.1186/s13058-025-02075-w","url":null,"abstract":"<p><strong>Background: </strong>Risk factors for breast cancer include obesity and hyperglycemia, which are associated with poor survival. Previous studies have used high-fat diets (HFDs) or Western-style diets to model dietary influences on breast cancer progression. However, these diets do not reflect the energy-dense, nutrient-poor diets that Americans typically consume. To address this gap in our understanding of the interplay between diet and breast cancer progression, we examined the effects of a modified standard American diet (SAD2) on mammary tumorigenesis in the MMTV-PyMT transgenic murine model and their FVB/N controls.</p><p><strong>Methods: </strong>MMTV-PyMT and FVB/N mice were fed normal chow or the experimental diet SAD2 for up to 12 weeks. We evaluated body weight, blood glucose, adiposity, cytokine, and tumor characteristics to measure SAD2 diet-induced changes in breast tumor development.</p><p><strong>Results: </strong>Increased body weight and adiposity were observed in MMTV SAD2-treated mice, consistent with the findings of shorter-term HFD studies. The SAD2 diet also resulted in earlier tumor initiation and progression and decreased survival in the SAD2-fed mice. While only modest changes were observed in circulating cytokines and metabolic parameters, the SAD2 tumors presented significant changes in oxidative DNA damage and advanced glycation end products (AGEs). These changes coincided with increases in the oncogenic transcription factor Foxm1 and the expression of Glut1. Both proteins are elevated in breast cancer patient samples but have not yet been linked to diet-induced effects.</p><p><strong>Conclusions: </strong>Using SAD2, we demonstrated that an American-style diet increased weight and adiposity while promoting the accumulation of oxidative DNA damage and AGEs and the expression of oncogenic Foxm1 within a relatively short diet interval. These data suggest that the SAD2 diet may offer insight into mechanisms that promote breast cancer aggressiveness and resistance to therapy.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"27 1","pages":"138"},"PeriodicalIF":5.6,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12296626/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144718956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MSN/STAT3 drives cancer stemness and chemoresistance via IL-6/LPAR1 ligand receptor complex in triple-negative breast cancer.","authors":"Cheng Hyun Lee, Soo Young Park, Jae Seok Lee, Da Sol Kim, Ha Yeon Kim, Min Ji Song, Seock-Ah Im, Kyung-Hun Lee, Dae-Won Lee, Ilias P Nikas, Ji Won Koh, So Hyeon Yang, Hyebin Lee, Han Suk Ryu","doi":"10.1186/s13058-025-02072-z","DOIUrl":"10.1186/s13058-025-02072-z","url":null,"abstract":"<p><strong>Background: </strong>Resistance to chemotherapy remains a major clinical challenge in triple-negative breast cancer (TNBC), an intrinsic subtype with limited available therapeutic options. The expression of moesin (MSN) is upregulated in TNBC patients, but little is known about the role of MSN in breast carcinogenesis.</p><p><strong>Methods: </strong>We investigated the MSN-dependent autocrine loop between extracellular interleukin 6 (IL-6) and NF-κB, along with a signaling cascade involving GTPase-mediated STAT3 phosphorylation. Various in vitro and in vivo assays were used to evaluate tumor initiation, growth, and stemness properties in TNBC models.</p><p><strong>Results: </strong>High MSN expression was correlated with shorter overall and disease-free survival in TNBC patients. In vivo, MSN promotes tumor initiation and growth. Mechanistically, MSN-mediated IL-6/NF-κB autoregulatory feedback enhances IL-6 transcription. IL-6 binding to LPAR1 activated MSN phosphorylation, which then sequentially phosphorylated the CDC42-PAK4 complex, triggering nuclear translocation of the pSTAT3-MSN complex. This led to pSTAT3-mediated activation of cancer stemness genes (IGFN1, EML1, and SRGN), contributing to Adriamycin resistance. Notably, combination treatment with the FDA-approved STAT3 inhibitor Atovaquone and Adriamycin restored drug sensitivity.</p><p><strong>Conclusions: </strong>Our findings uncover the critical role of MSN in regulating STAT3-mediated cancer stemness via the IL-6/NF-κB signaling axis. These results provide a strong rationale for repositioning STAT3 inhibitors such as Atovaquone as a therapeutic strategy in Adriamycin-resistant TNBC patients exhibiting pSTAT3-MSN complex upregulation.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"27 1","pages":"136"},"PeriodicalIF":5.6,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12281688/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144692116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retinoic acid-induced 2 deficiency impairs genomic stability in breast cancer.","authors":"Lena Boettcher, Sarah Greimeier, Kerstin Borgmann, Shabbir S Mughal, Bernhard Ellinger, Kai Bartkowiak, Bernd Zobiak, Antonio V Failla, Pascal Steffen, Ellen Claus, Katharina Besler, Christopher Buccitelli, Violetta Schaaf, Ann-Kathrin Ozga, Simona Parretta, Svenja Schneegans, Wael Y Mansour, Jan O Korbel, Hartmut Schlueter, Benedikt Brors, Klaus Pantel, Harriet Wikman, Stefan Werner","doi":"10.1186/s13058-025-02085-8","DOIUrl":"10.1186/s13058-025-02085-8","url":null,"abstract":"<p><strong>Background: </strong>Genome instability is a fundamental feature and hallmark of cancer, associated with aggressiveness, drug resistance and poor prognosis. RAI2 was initially identified as a novel metastasis suppressor protein specifically associated with the presence of disseminated tumour cells in the bone marrow of breast cancer patients, but its molecular function is largely unknown.</p><p><strong>Methods: </strong>We analysed the consequences of RAI2 depletion on gene expression and genomic stability in luminal breast cancer cell lines, performed cytotoxicity profiling using a library of pharmacologically active compounds, and characterized a potential function of the RAI2 protein in the DNA damage response. We performed in silico validation in different breast cancer datasets.</p><p><strong>Results: </strong>Analysis of clinical samples revealed that in primary breast tumours, low RAI2 gene expression is significantly associated with genomically unstable tumours and poor prognosis. RAI2 depletion in breast cancer cell lines resulted in loss of mitotic fidelity characterized by prolonged mitosis with increased chromosome segregation errors and micronuclei formation. Drug screening revealed increased sensitivity of RAI2-depleted breast cancer cells to topoisomerase I and Aurora A inhibitors. We also found that genotoxic stress induces the RAI2 protein, which has an affinity for and colocalises with poly-(ADP-ribose). We validated the association of RAI2 gene expression with DNA repair capacity in clinical samples.</p><p><strong>Conclusions: </strong>Our findings support, for the first time, a functional role of RAI2 in the maintenance of genomic stability. Understanding the underlying the molecular mechanism could help to improve patient diagnosis and treatment.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"27 1","pages":"137"},"PeriodicalIF":5.6,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12285165/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144692117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Trastuzumab deruxtecan in patients with active brain metastases from HER2-positive/low metastatic breast cancer: a retrospective multicenter real-world study.","authors":"Fangfang Duan, Xin Hua, Wei Lu, Xingxing Gui, Jingdun Xie, Xudong Wang, Yuyu Ma, Wenyu Zhai, Wen Xia","doi":"10.1186/s13058-025-02088-5","DOIUrl":"10.1186/s13058-025-02088-5","url":null,"abstract":"","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"27 1","pages":"135"},"PeriodicalIF":7.4,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12281696/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144683470","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic value of FDG PET/CT in de novo stage IV breast cancer patients treated with cyclin-dependent kinase 4/6 inhibitors.","authors":"Wonseok Whi, Junghoon Shin, Ji-Yeon Kim, Hee Kyung Ahn, Yeon Hee Park, Jin Seok Ahn, Hyunjong Lee","doi":"10.1186/s13058-025-02087-6","DOIUrl":"10.1186/s13058-025-02087-6","url":null,"abstract":"<p><strong>Background: </strong>De novo stage IV breast cancer presents a significant challenge due to its advanced nature and poor prognosis. Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) combined with endocrine therapy have emerged as effective treatments for hormone receptor-positive HER2-negative breast cancers. However, predicting patient responses remains difficult. This study aimed to evaluate the prognostic value of FDG PET/CT in predicting therapeutic response and progression-free survival (PFS) in patients with de novo stage IV breast cancer undergoing CDK4/6i treatment.</p><p><strong>Methods: </strong>A retrospective analysis was conducted on 106 patients with de novo stage IV breast cancer who were treated with CDK4/6i between 2016 and 2023. All patients underwent FDG PET/CT before treatment and 68 patients underwent follow-up FDG PET/CT. The relationship between SUVmax and clinicopathological factors was analyzed using t-test and ANOVA. PFS was assessed via Kaplan-Meier analysis and Cox proportional hazards models, with a focus on SUVmax parameters, including the SUVmax values of the primary tumor (SUVmax_primary), metastatic regional lymph node (SUVmax_LN), distant metastasis (SUVmax_distant), the highest SUVmax value along the entire body (SUVmax_whole), and their proportional responses during follow-up.</p><p><strong>Results: </strong>Lower Ki-67 score (1+) was significantly associated with lower SUVmax_primary (P = 0.002) and SUVmax_whole (P = 0.007) scores than higher Ki-67 scores. SUVmax_whole was a significant predictor of PFS at baseline (hazard ratio, HR = 2.45, P = 0.012) and follow-up (HR = 4.32, P = 0.002). Patients with higher SUVmax reductions showed better PFS outcomes (HR = 0.22, P < 0.001). Neither the initial SUVmax of the primary lesion (HR = 1.81, P = 0.067) nor its response (HR = 0.49, P = 0.063) on follow-up were significant predictors of PFS.</p><p><strong>Conclusions: </strong>This study highlights the prognostic value of FDG PET/CT in evaluating the therapeutic response to CDK4/6i in de novo stage IV breast cancer. SUVmax_whole and its proportional response serve as important predictors of PFS, emphasizing the need to assess metabolic activity across the entire body rather than just in the primary tumor.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"27 1","pages":"134"},"PeriodicalIF":7.4,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12275393/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144668822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fibroblast growth factor receptor signaling modulates cholesterol storage in a SOAT1-dependent manner to promote mammary tumor cell invasion.","authors":"Jennifer E Tuokkola, Lyndsay E Reese, Ying Wang, Christine H O'Connor, Jillian G VanTreeck, Annisa H Rumahorbo, Kathryn L Schwertfeger","doi":"10.1186/s13058-025-02084-9","DOIUrl":"10.1186/s13058-025-02084-9","url":null,"abstract":"<p><p>Signaling by fibroblast growth factor receptors (FGFRs) is active in up to 85% of breast cancers and results in enhanced proliferation, migration, and invasion of tumor cells. Here, we show that FGFR signaling regulates cholesterol metabolism in breast cancer. Specifically, we demonstrate that FGFR activation promotes cellular cholesterol storage by upregulating expression of the enzyme sterol O-acyltransferase 1 (SOAT1). Moreover, we demonstrate that inhibition of SOAT1 attenuates FGFR-driven colony formation and invasion in tumor cells, which correlates with reduced expression of matrix metalloproteinase expression. Furthermore, genetic knockdown of SOAT1 decreases mammary tumor growth in vivo. Taken together, these findings suggest a largely undiscovered metabolic role for FGFR signaling in regulating cholesterol metabolism in breast cancer and present a therapeutic vulnerability that could be targeted in FGFR-driven cancers.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"27 1","pages":"132"},"PeriodicalIF":7.4,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12261779/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144643985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multi-transcriptomics predicts clinical outcome in systemically untreated breast cancer patients with extensive follow-up.","authors":"Thi T N Do, Ines Block, Mark Burton, Kristina P Sørensen, Martin J Larsen, Anne Marie Bak Jylling, Bent Ejlertsen, Anne-Vibeke Lænkholm, Qihua Tan, Torben A Kruse, Mads Thomassen","doi":"10.1186/s13058-025-02061-2","DOIUrl":"10.1186/s13058-025-02061-2","url":null,"abstract":"<p><strong>Background: </strong>Prognostic tools for determining patients with indolent breast cancers (BCs) are far from optimal, leading to extensive overtreatment. Several studies have demonstrated mRNAs, lncRNAs and miRNAs to have prognostic potential in BC. Because mRNAs, lncRNAs, and miRNAs capture distinct transcriptomic information, we hypothesized that combining them would improve classification performance.</p><p><strong>Methods: </strong>Our pair-matched design study included fresh frozen primary tumor samples from 160 lymph node negative and systemically untreated BC patients of which 80 developed recurrence while 80 remained recurrence-free (mean follow-up of 20.9 years). We integrated three classes of RNA and subsequently performed classification using seven machine learning methods followed by a voting scheme.</p><p><strong>Results: </strong>Under the criteria of ≥ 90% sensitivity, individual classifications resulted in specificities ranging from 74-91% for the integrated dataset and 56-66%, 58-71% and 69-86% for mRNAs, lncRNAs and miRNAs individually. The specificity level for the multi-transcriptomic dataset was 85% after voting while it was 38%, 48% and 82% for mRNAs, lncRNAs and miRNAs, respectively. In the clinical setting, very high sensitivity may be requested. In the most stringent clinical setting with a sensitivity of 99%, the integrated dataset also outperformed the others with a specificity of 41% compared to 0%, 9% and 28% for mRNAs, lncRNAs and miRNAs, respectively.</p><p><strong>Conclusion: </strong>Our results strongly suggest an improvement of prognostic power for classification using an integrated dataset compared to individual classes of RNA and thus encourage researches to opt for an integration of datasets rather than analyzing them separately.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"27 1","pages":"133"},"PeriodicalIF":7.4,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12261547/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144643986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The impact of a mainstream genetic testing pathway and socioeconomic factors on the uptake of germline genetic testing in breast cancer patients: results of the nationwide GENE-SMART study.","authors":"Chiem Leonardo de Jong, Sabine Siesling, Ghita Carola Wilhelmina Maria Puts, Agnes Jager, Margreet Geertruda Elia Maria Ausems","doi":"10.1186/s13058-025-02081-y","DOIUrl":"10.1186/s13058-025-02081-y","url":null,"abstract":"<p><strong>Background: </strong>Genetic testing in breast cancer patients is important for the patient's local and systemic treatment choices and follow-up, as well as for their family members. Not all eligible patients currently undergo genetic testing and disparities persist in genetic testing uptake. It is unknown on the large scale whether pre-test counselling by non-genetic healthcare professionals (HCPs)-mainstream genetic testing (MGT) - improves overall genetic testing uptake and reduces disparities. We examined the impact of MGT on germline genetic testing uptake in general and in subgroups of socioeconomic status (SES) in particular.</p><p><strong>Methods: </strong>In this retrospective nationwide cohort study, we selected all breast cancer patients from the Netherlands Cancer Registry who were eligible for genetic testing according to patient and tumour characteristics under the Dutch guidelines and who were diagnosed between 1-Jan-2017 and 31-Dec-2022. The primary outcome was genetic testing uptake. The influence of MGT and SES on overall uptake and uptake across different SES levels was evaluated using chi-squared tests and multivariable logistic regression analyses.</p><p><strong>Results: </strong>A total of 12,071 breast cancer patients were included. Overall genetic testing uptake was 67%: 78% for MGT versus 63% in referral to a genetics department (RGD) (p < 0.001) with significantly higher odds of receiving genetic testing for MGT versus RGD (OR 2.48, 95% CI 2.14-2.87). Patients with low SES showed significantly lower odds of receiving genetic testing compared to those with a high SES (OR 0.71, 95% CI 0.61-0.83). In MGT, no significant difference was found between low and high SES in the likelihood of receiving genetic testing (OR 0.75, 95% CI 0.50-1.13).</p><p><strong>Conclusions: </strong>MGT significantly increases genetic testing uptake among all eligible patients and across all SES subgroups, strongly encouraging further implementation of MGT. Educating HCPs about current disparities in genetic testing is essential to improve health equity in breast cancer care.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"27 1","pages":"129"},"PeriodicalIF":7.4,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12257806/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144627536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}