Breast Cancer Research最新文献

{"title":"Toll-Like receptor 3-mediated interferon-β production is suppressed by oncostatin m and a broader epithelial-mesenchymal transition program.","authors":"Noah M Chernosky, Ilaria Tamagno, Kelsey L Polak, E Ricky Chan, Xueer Yuan, Mark W Jackson","doi":"10.1186/s13058-024-01918-2","DOIUrl":"10.1186/s13058-024-01918-2","url":null,"abstract":"<p><strong>Background: </strong>Patients with Triple Negative Breast Cancer (TNBC) currently lack targeted therapies, and consequently face higher mortality rates when compared to patients with other breast cancer subtypes. The tumor microenvironment (TME) cytokine Oncostatin M (OSM) reprograms TNBC cells to a more stem-like/mesenchymal state, conferring aggressive cancer cell properties such as enhanced migration and invasion, increased tumor-initiating capacity, and intrinsic resistance to the current standards of care. In contrast to OSM, Interferon-β (IFN-β) promotes a more differentiated, epithelial cell phenotype in addition to its role as an activator of anti-tumor immunity. Importantly, OSM suppresses the production of IFN-β, although the mechanism of IFN-β suppression has not yet been elucidated.</p><p><strong>Methods: </strong>IFN-β production and downstream autocrine signaling were assessed via quantitative real-time PCR (qRT-PCR) and Western blotting in TNBC cells following exposure to OSM. RNA-sequencing (RNA-seq) was used to assess an IFN-β metagene signature, and to assess the expression of innate immune sensors, which are upstream activators of IFN-β. Cell migration was assessed using an in vitro chemotaxis assay. Additionally, TNBC cells were exposed to TGF-β1, Snail, and Zeb1, and IFN-β production and downstream autocrine signaling were assessed via RNA-seq, qRT-PCR, and Western blotting.</p><p><strong>Results: </strong>Here, we identify the repression of Toll-like Receptor 3 (TLR3), an innate immune sensor, as the key molecular event linking OSM signaling and the repression of IFN-β transcription, production, and autocrine IFN signaling. Moreover, we demonstrate that additional epithelial-mesenchymal transition-inducing factors, such as TGF-β1, Snail, and Zeb1, similarly suppress TLR3-mediated IFN-β production and signaling.</p><p><strong>Conclusions: </strong>Our findings provide a novel insight into the regulation of TLR3 and IFN-β production in TNBC cells, which are known indicators of treatment responses to DNA-damaging therapies. Furthermore, strategies to stimulate TLR3 in order to increase IFN-β within the TME may be ineffective in stem-like/mesenchymal cells, as TLR3 is strongly repressed. Rather, we propose that therapies targeting OSM or OSM receptor would reverse the stem-like/mesenchymal program and restore TLR3-mediated IFN-β production within the TME, facilitating improved responses to current therapies.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"26 1","pages":"167"},"PeriodicalIF":7.4,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11590466/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142733952","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":"A systematic review of candidate genes and their relevant pathways for metastasis among adults diagnosed with breast cancer.","authors":"Gina M Gehling, Miad Alfaqih, Lisiane Pruinelli, Angela Starkweather, Jennifer R Dungan","doi":"10.1186/s13058-024-01914-6","DOIUrl":"10.1186/s13058-024-01914-6","url":null,"abstract":"<p><strong>Background: </strong>Presently incurable, metastatic breast cancer is estimated to occur in as many as 30% of those diagnosed with early-stage breast cancer. Timely and accurate identification of those at risk for developing metastasis using validated biomarkers has the potential to have profound impact on overall survival rates. Our primary goal was to conduct a systematic review and synthesize the existing body of scientific knowledge on the candidate genes and their respective single nucleotide polymorphisms associated with metastasis-related outcomes among patients diagnosed with breast cancer. This knowledge is critical to inform future hypothesis-driven and validation research aimed at enhancing clinical decision-making for breast cancer patients.</p><p><strong>Methods: </strong>Using PRISMA guidelines, literature searches were conducted on September 13th, 2023, using PubMed and Embase databases. The systematic review protocol was registered with INPLASY (DOI: https://doi.org/10.37766/inplasy2024.8.0014 ). Covidence software was used to facilitate the screening and article extraction processes. Peer-reviewed articles were selected if authors reported on single nucleotide polymorphisms directly associated with metastasis among adults diagnosed with breast cancer.</p><p><strong>Findings: </strong>We identified 451 articles after 44 duplicates were removed resulting in 407 articles to be screened for study inclusion. Three reviewers completed the article screening process which resulted in 86 articles meeting the study inclusion criteria. Sampling varied across studies with the majority utilizing a case-control design (n = 75, 87.2%), with sample sizes ranging from 23 to 1,017 participants having mean age 50.65 ± 4.50 (min-max: 20-75). The synthesis of this internationally generated evidence revealed that the scientific area on the underlying biological contributions to breast cancer metastasis remains predominantly exploratory in nature (n = 74, 86%). Of the 12 studies with reported power analyses, only 9 explicitly stated the power values which ranged from 47.88 to 99%.</p><p><strong>Discussion: </strong>Understanding the underlying biological mechanisms contributing to metastasis is a critical component for precision oncological therapeutics and treatment approaches. Current evidence investigating the contribution of SNPs to the development of metastasis is characterized by underpowered candidate gene studies. To inform individualized precision health practices and improve breast cancer survival outcomes, future hypothesis-driven research is needed to replicate these associations in larger, more diverse datasets.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"26 1","pages":"165"},"PeriodicalIF":7.4,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11590482/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142733946","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":"Characterization of novel small molecule inhibitors of estrogen receptor-activation function 2 (ER-AF2).","authors":"Jane Foo, Francesco Gentile, Shabnam Massah, Helene Morin, Kriti Singh, Joseph Lee, Jason Smith, Fuqiang Ban, Eric LeBlanc, Robert Young, Natalie Strynadka, Nada Lallous, Artem Cherkasov","doi":"10.1186/s13058-024-01926-2","DOIUrl":"10.1186/s13058-024-01926-2","url":null,"abstract":"<p><p>Up to 40% of patients with estrogen receptor (ER)-positive breast cancer will develop resistance against the majority of current ER-directed therapies. Resistance can arise through various mechanisms such as increased expression levels of coregulators, and key mutations acquired in the receptor's ligand binding domain rendering it constitutively active. To overcome these resistance mechanisms, we explored targeting the ER Activation Function 2 (AF2) site, which is essential for coactivator binding and activation. Using artificial intelligence and the deep docking methodology, we virtually screened > 1 billion small molecules and identified 290 potential AF2 binders that were then characterized and validated through an iterative screening pipeline of cell-based and cell-free assays. We ranked the compounds based on their ability to reduce the transcriptional activity of the estrogen receptor and the viability of ER-positive breast cancer cells. We identified a lead compound, VPC-260724, which inhibits ER activity at low micromolar range. We confirmed its direct binding to the ER-AF2 site through a PGC1α peptide displacement experiment. Using proximity ligation assays, we showed that VPC-260724 disrupts the interaction between ER-AF2 and the coactivator SRC-3 and reduces the expression of ER target genes in various breast cancer models including the tamoxifen resistant cell line TamR3. In conclusion, we developed a novel ER-AF2 binder, VPC-260724, which shows antiproliferative activity in ER-positive breast cancer models. The use of an ER-AF2 inhibitor in combination with current treatments may provide a novel complementary therapeutic approach to target treatment resistance in ER-positive breast cancer.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"26 1","pages":"168"},"PeriodicalIF":7.4,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11590367/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142733947","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":"Low-dose tamoxifen treatment reduces collagen organisation indicative of tissue stiffness in the normal breast: results from the KARISMA randomised controlled trial.","authors":"Sara Göransson, Pablo Hernández-Varas, Mattias Hammarström, Roxanna Hellgren, Magnus Bäcklund, Kristina Lång, Ann H Rosendahl, Mikael Eriksson, Signe Borgquist, Staffan Strömblad, Kamila Czene, Per Hall, Marike Gabrielson","doi":"10.1186/s13058-024-01919-1","DOIUrl":"10.1186/s13058-024-01919-1","url":null,"abstract":"<p><strong>Background: </strong>Tissue stiffness, dictated by organisation of interstitial fibrillar collagens, increases breast cancer risk and contributes to cancer progression. Tamoxifen is a standard treatment for receptor-positive breast cancer and is also aproved for primary prevention. We investigated the effect of tamoxifen and its main metabolites on the breast tissue collagen organisation as a proxy for stiffness and explored the relationship between mammographic density (MD) and collagen organisation.</p><p><strong>Material and methods: </strong>This sub-study of the double-blinded dose-determination trial, KARISMA, included 83 healthy women randomised to 6 months of 20, 10, 5, 2.5, and 1 mg of tamoxifen or placebo. Ultrasound-guided core-needle breast biopsies collected before and after treatment were evaluated for collagen organisation by polarised light microscopy.</p><p><strong>Results: </strong>Tamoxifen reduced the amount of organised collagen and overall organisation, reflected by a shift from heavily crosslinked thick fibres to thinner, less crosslinked fibres. Collagen remodelling correlated with plasma concentrations of tamoxifen metabolites. MD change was not associated with changes in amount of organised collagen but was correlated with less crosslinking in premenopausal women.</p><p><strong>Conclusions: </strong>In this study of healthy women, tamoxifen decreased the overall organisation of fibrillar collagens, and consequently, the breast tissue stiffness. These stromal alterations may play a role in the well-established preventive and therapeutic effects of tamoxifen. Trial registration ClinicalTrials.gov ID: NCT03346200. Registered November 1st, 2017. Retrospectively registered.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"26 1","pages":"163"},"PeriodicalIF":7.4,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11590516/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142733950","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 shared genetic landscape of polycystic ovary syndrome and breast cancer: convergence on ER + breast cancer but not ER- breast cancer.","authors":"Kaixin Bi, Miaoran Chen, Qianru Zhao, Tongtong Yang, Wenjia Xie, Wenqi Ma, Hongyan Jia","doi":"10.1186/s13058-024-01923-5","DOIUrl":"10.1186/s13058-024-01923-5","url":null,"abstract":"<p><strong>Background: </strong>The clinically high comorbidity between polycystic ovary syndrome (PCOS) and breast cancer (BC) has been extensively reported. However, limited knowledge exists regarding their shared genetic basis and underlying mechanisms.</p><p><strong>Method: </strong>Leveraging summary statistics from the largest genome-wide association studies (GWASs) to date, we conducted a comprehensive genome-wide cross-trait analysis of PCOS and BC. A variety of genetic statistical methods were employed to uncover potential shared genetic causes.</p><p><strong>Results: </strong>Our analysis revealed genetic overlap between the three trait pairs. After partitioning the genome into 2,495 independent regions, we identified two loci, chr8: 75,011,700-76,295,483 and chr17: 6,305,079-7,264,458, with significant localized genetic correlations. Pleiotropic analysis under a composite null hypothesis identified 1,183 significant pleiotropic single nucleotide polymorphisms (SNPs) across three trait pairs. FUMA mapped 26 pleiotropic loci, with regions 16q12.2 and 6q25.1 duplicated across all three trait pairs, while COLOC detected three loci with colocalization evidence. Gene-based analysis identified 23 unique candidate pleiotropic genes, including the FTO shared by all trait pairs, as well as SER1, RALB, and others in two trait pairs. Pathway enrichment analysis further highlighted key biological pathways, primarily involving the significant biological pathways were the metabolism of regulation of autophagy, regulation of cellular catabolic process, and positive regulation of catabolic process. Latent Heritable Confounder Mendelian randomization (LHC-MR) supported a positive causal relationship between PCOS and both BCALL and ERPBC but not with ERNBC.</p><p><strong>Conclusion: </strong>In conclusion, our genome-wide cross-trait analysis identified a shared genetic basis between PCOS and BC, specific identical genetic mechanisms and causality between PCOS and various BC subtypes, which could better explains the genetics of the co-morbidity of PCOS and ERPBC rather than PCOS and ERNBC. These findings provide new insights into the biological mechanisms underlying the co-morbidity of these two complex diseases, which have important implications for clinical disease intervention, treatment, and improved prognosis.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"26 1","pages":"161"},"PeriodicalIF":7.4,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11587662/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142717494","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":"Immune landscape of the tumour microenvironment in Ethiopian breast cancer patients.","authors":"Meron Yohannes, Zelalem Desalegn, Marcus Bauer, Kathrin Stückrath, Endale Anberbir, Yonas Bekuretsion, Mathewos Assefa, Tariku Wakuma, Yasin Worku, Pablo S C Santos, Lesley Taylor, Adamu Adissie, Claudia Wickenhauser, Chiara Massa, Martina Vetter, Eva Johanna Kantelhardt, Barbara Seliger, Tamrat Abebe","doi":"10.1186/s13058-024-01916-4","DOIUrl":"10.1186/s13058-024-01916-4","url":null,"abstract":"<p><strong>Background: </strong>The clinical management of breast cancer (BC) is mainly based on the assessment of receptor expression by tumour cells. However, there is still an unmet need for novel biomarkers important for prognosis and therapy. The tumour immune microenvironment (TIME) is thought to play a key role in prognosis and therapy selection, therefore this study aimed to describe the TIME in Ethiopian BC patients.</p><p><strong>Methods: </strong>RNA was isolated from formalin-fixed paraffin-embedded (FFPE) tissue from 82 women with BC. Expression of PAM50 and 54 immune genes was analysed using the Nanostring platform and differentially expressed genes (DEGs) were determined using ROSALIND^®. The abundance of different cell populations was estimated using Nanostring's cell type profiling module, while tumour infiltrating lymphocytes (TILs) were analysed using haematoxylin and eosin (H&E) staining. In addition, the PIK3CA gene was genotyped for three hotspot mutations using qPCR. Kaplan-Meier survival analysis and log-rank test were performed to compare the prognostic relevance of immune subgroups.</p><p><strong>Results: </strong>Four discrete immune phenotypes (IP1-4) were identified through hierarchical clustering of immune gene expression data. These IPs were characterized by DEGs associated with both immune activation and inhibition as well as variations in the extent of immune infiltration. However, there were no significant differences regarding PIK3CA mutations between the IPs. A downregulation of immune suppressive and activating genes and the lowest number of infiltrating immune cells were found in IP2, which was associated with luminal tumours. In contrast, IP4 displayed an active TME chracterized by an upregulation of cytotoxic genes and the highest density of immune cell infiltrations, independent of the specific intrinsic subtype. IP1 and IP3 exhibited intermediate characteristics. The IPs had a prognostic relevance and patients with an active TME had improved overall survival compared to IPs with a significant downregulation of the majority of immune genes.</p><p><strong>Conclusion: </strong>Immune gene expression profiling identified four distinct immune contextures of the TME with unique gene expression patterns and immune infiltration. The classification into distinct immune subgroups may provide important information regarding prognosis and the selection of patients undergoing conventional treatments or immunotherapies.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"26 1","pages":"162"},"PeriodicalIF":7.4,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11587711/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142717493","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":"Quantification of intratumoral heterogeneity using habitat-based MRI radiomics to identify HER2-positive, -low and -zero breast cancers: a multicenter study.","authors":"Haoquan Chen, Yulu Liu, Jiaqi Zhao, Xiaoxuan Jia, Fan Chai, Yuan Peng, Nan Hong, Shu Wang, Yi Wang","doi":"10.1186/s13058-024-01921-7","DOIUrl":"10.1186/s13058-024-01921-7","url":null,"abstract":"<p><strong>Background: </strong>Human epidermal growth factor receptor 2-targeted (HER2) therapy with antibody-drug conjugates has proven effective for patients with HER2-low breast cancer. However, intratumoral heterogeneity (ITH) poses a great challenge in identifying HER2-low tumors. ITH signatures were developed by quantifying ITH to differentiate HER2-positive, -low and -zero breast cancers.</p><p><strong>Methods: </strong>This retrospective study included 614 patients from two institutions. The study was structured into two primary tasks: task 1 was to differentiate between HER2-positive and -negative tumors, followed by task 2 to differentiate HER2-low and -zero tumors. Whole-tumor radiomics features and habitat radiomics features were extracted from MRI to construct the radiomics and ITH signatures. Multivariable logistic regression analysis was used to determine significant independent predictors. A combined model integrating significant clinicopathologic variables, radiomics signature, and ITH signature was developed for task (1) Subsequently, the better-performing model was established using the same approach for task (2) The area under the receiver operating characteristic curve (AUC) was used to assess the performance of each model.</p><p><strong>Results: </strong>Task 1 comprised 614 patients (training, n = 348; validation, n = 149; and test cohorts, n = 117). Task 2 encompassed 501 patients (training, n = 283; validation, n = 122; and test cohorts, n = 96). For task1, the ITH signature showed outstanding performance, achieving AUCs of 0.81, 0.81, and 0.81 in the training, validation and test cohorts, respectively. The combined model achieved improved performance, with AUCs of 0.83, 0.84 and 0.83 across the three cohorts, respectively. For task2, the ITH signature maintained superior performance, with AUCs of 0.94, 0.93 and 0.84 across the training, validation and test cohorts, respectively. Multivariable logistic regression analysis indicated that none of the clinicopathologic characteristics were retained as predictors associated with odds of HER2-low tumors.</p><p><strong>Conclusions: </strong>Our study developed ITH signatures that quantified ITH using habitat-based MRI radiomics, achieving outstanding performance in differentiating HER2-postive and -negative tumors, and further differentiating HER2-low and -zero breast cancers.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"26 1","pages":"160"},"PeriodicalIF":7.4,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11583526/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142693095","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":"Exposure to air pollutants and breast cancer risk: mediating effects of metabolic health biomarkers in a nested case-control study within the E3N-Generations cohort.","authors":"Benoît Mercoeur, Béatrice Fervers, Thomas Coudon, Hwayoung Noh, Camille Giampiccolo, Lény Grassot, Elodie Faure, Florian Couvidat, Gianluca Severi, Francesca Romana Mancini, Pascal Roy, Delphine Praud, Amina Amadou","doi":"10.1186/s13058-024-01913-7","DOIUrl":"10.1186/s13058-024-01913-7","url":null,"abstract":"<p><strong>Background: </strong>Growing epidemiological evidence suggests an association between exposure to air pollutants and breast cancer. Yet, the underlying mechanisms remain poorly understood. This study explored the mediating role of thirteen metabolic health biomarkers in the relationship between exposure to three air pollutants, i.e. nitrogen dioxide (NO₂), polychlorinated biphenyls 153 (PCB153), and benzo[a]pyrene (BaP), and breast cancer risk.</p><p><strong>Methods: </strong>We used data from a nested case-control study within the French national prospective E3N-Generations cohort, involving 523 breast cancer cases and 523 matched controls. The four-way decomposition mediation of total effects for thirteen biomarkers was applied to estimate interaction and mediation effects (controlled direct, reference interaction, mediated interaction, and pure indirect effects).</p><p><strong>Results: </strong>The analyses indicated a significant increase in breast cancer risk associated with BaP exposure (odds ratio (OR)_{Q4 vs Q1} = 2.32, 95% confidence intervals (CI): 1.00-5.37). PCB153 exposure showed a positive association only in the third quartile (OR_{Q3 vs Q1} = 2.25, CI 1.13-4.57), but it appeared to be non-significant in the highest quartile (OR_{Q4 vs Q1} = 2.07, CI 0.93-4.61). No association was observed between NO₂ exposure and breast cancer risk. Estradiol was associated with an increased risk of breast cancer (OR per one standard deviation (SD) increment = 1.22, CI 1.05-1.42), while thyroid-stimulating hormone was inversely related to breast cancer risk (OR per 1SD increase = 0.87, CI 0.75-1.00). We observed a suggestive mediated effect of the association between the three pollutants and breast cancer risk, through albumin, high-density lipoproteins cholesterol, low-density lipoprotein cholesterol, parathormone, and estradiol.</p><p><strong>Conclusion: </strong>Although limited by a lack of statistical power, this study provides relevant insights into the potential mediating role of certain biomarkers in the association between air pollutant exposure and breast cancer risk, highlighting the need for further in-depth studies in large populations.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"26 1","pages":"159"},"PeriodicalIF":7.4,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11568591/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142644829","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":"Body mass index and breast cancer risk in premenopausal and postmenopausal East Asian women: a pooled analysis of 13 cohort studies.","authors":"Keiko Wada, Koshi Kuboyama, Sarah Krull Abe, Md Shafiur Rahman, Md Rashedul Islam, Eiko Saito, Chisato Nagata, Norie Sawada, Akiko Tamakoshi, Xiao-Ou Shu, Ritsu Sakata, Atsushi Hozawa, Seiki Kanemura, Hidemi Ito, Yumi Sugawara, Sue K Park, Sun-Seog Kweon, Ayami Ono, Takashi Kimura, Wanqing Wen, Isao Oze, Min-Ho Shin, Aesun Shin, Jeongseon Kim, Jung Eun Lee, Keitaro Matsuo, Nathaniel Rothman, You-Lin Qiao, Wei Zheng, Paolo Boffetta, Manami Inoue","doi":"10.1186/s13058-024-01907-5","DOIUrl":"10.1186/s13058-024-01907-5","url":null,"abstract":"<p><strong>Background: </strong>It has been suggested that the association between body mass index and breast cancer risk differs between Asian women and Western women. We aimed to assess the associations between body mass index and breast cancer incidence in East Asian women.</p><p><strong>Methods: </strong>Pooled analyses were performed using individual participant data of 319,189 women from 13 cohort studies in Japan, Korea, and China. Participants' height and weight were obtained by measurement or self-reports at cohort baseline. Breast cancer was defined as code C50.0-C50.9 according to the International Classification. Using a Cox proportional hazards model, hazard ratios of breast cancer were estimated for each body mass index category, with the reference group set as the group with a body mass index of 21 to < 23 kg/m². The hazard ratio for a 5 kg/m² increase in body mass index was also calculated.</p><p><strong>Results: </strong>During a mean 16.6 years of follow-up, 4819 women developed breast cancer. Similar to Westerners, a steady increase in breast cancer risk with increasing body mass index was observed in postmenopausal women, but the slope of the risk increase appeared to slow at a body mass index of 26-28 kg/m². In premenopausal women, the inverse association seen in Westerners was not observed. The risk of developing breast cancer after 50 years of age increased slightly with increasing body mass index, which was more pronounced in the older birth cohort. There was no significant association between body mass index and the risk of developing breast cancer before 50 years of age, but the risk estimates changed from positive to negative as the birth cohort got younger.</p><p><strong>Conclusions: </strong>In East Asia, the role of body mass index in breast cancer in premenopausal women may be changing along with the increase in obesity and breast cancer. The increased risk of postmenopausal breast cancer with a higher body mass index was as robust as that of Western women.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"26 1","pages":"158"},"PeriodicalIF":7.4,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11566150/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142631216","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":"Automatic segmentation-based multi-modal radiomics analysis of US and MRI for predicting disease-free survival of breast cancer: a multicenter study.","authors":"Lang Xiong, Xiaofeng Tang, Xinhua Jiang, Haolin Chen, Binyan Qian, Biyun Chen, Xiaofeng Lin, Jianhua Zhou, Li Li","doi":"10.1186/s13058-024-01909-3","DOIUrl":"10.1186/s13058-024-01909-3","url":null,"abstract":"<p><strong>Background: </strong>Several studies have confirmed the potential value of applying radiomics to predict prognosis of breast cancer. However, the tumor segmentation in these studies depended on delineation or annotation of breast cancer by radiologist, which is often laborious, tedious, and vulnerable to inter- and intra-observer variability. Automatic segmentation is expected to overcome this difficulty. Herein, we aim to investigate the value of automatic segmentation-based multi-modal radiomics signature and magnetic resonance imaging (MRI) features in predicting disease-free survival (DFS) of patients diagnosed with invasive breast cancer.</p><p><strong>Methods: </strong>This retrospective multicenter study included a total of 643 female patients with invasive breast cancer who underwent preoperative ultrasound (US) and MRI for prognostic analysis. Data (n = 480) from center 1 were divided into training and internal testing sets, while data (n = 163) from centers 2 and 3 were analyzed as the external testing set. We developed automatic segmentation frameworks for tumor segmentation by deep learning. Then, Least absolute shrinkage and selection operator Cox regression was used to select features to construct radiomics signature, and corresponding radiomics score (Rad-score) was calculated. Finally, six models for predicting DFS were constructed by using Cox regression and assessed in terms of discrimination, calibration, and clinical usefulness.</p><p><strong>Results: </strong>The multi-modal radiomics signature combining intra- and peri-tumoral radiomics signatures of US and MRI achieved a higher C-index in the internal (0.734) and external (0.708) testing sets than most other radiomics signatures in predicting DFS, and successfully stratified patients into low- and high-risk groups. The multi-modal clinical imaging model combining the multi-modal Rad-score and clinical traditional MRI model-score resulted in a higher C-index (0.795) than other models in the external testing set, and it had a better calibration and higher clinical benefit.</p><p><strong>Conclusions: </strong>This study demonstrates that the multi-modal radiomics signature derived from automatic segmentations of US and MRI is a promising risk stratification biomarker for breast cancer, and highlights that the appropriate combination of multi-modal radiomics signature, clinical characteristics, and MRI feature can improve performance of individualized DFS prediction, which might assist in guiding decision-making related to breast cancer.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"26 1","pages":"157"},"PeriodicalIF":7.4,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11555850/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142631212","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}