Breast Cancer Research最新文献

{"title":"miRNA panel from HER2+ and CD24+ plasma extracellular vesicle subpopulations as biomarkers of early-stage breast cancer.","authors":"Griffin B Spychalski, Andrew A Lin, Stephanie J Yang, Hanfei Shen, Jean Rosario, Kyle Tien, Kate French, Miriyam Ghali, Stephanie Yee, Melinda Yin, Michael D Feldman, Emily F Conant, Susan P Weinstein, Erica L Carpenter, David Issadore, Anupma Nayak","doi":"10.1186/s13058-025-02029-2","DOIUrl":"10.1186/s13058-025-02029-2","url":null,"abstract":"<p><strong>Background: </strong>Mammography screening has improved early breast cancer detection, leading to reduced mortality and lower rates of advanced breast cancer. However, mammography has a high false positive rate that results in over a million invasive breast biopsies of benign lesions in the US each year. Therefore, there is a need for noninvasive, blood-based diagnostics that can accurately assess risk of malignancy for women with indeterminate lesions identified by mammography, such as BI-RADS category 4 breast lesions. The aim of this study is to identify biomarkers from multiplexed extracellular vesicle liquid biopsy that can accurately classify mammographically detected BI-RADS 4 lesions.</p><p><strong>Methods: </strong>We analyzed plasma from 113 prospectively enrolled subjects with BI-RADS 4 breast lesions, including 86 women with benign lesions and 27 women with malignant lesions (including 12 with stage I invasive carcinoma and 14 with ductal carcinoma in situ). None of the invasive carcinomas were metastatic. From each plasma sample, we used track etched magnetic nanopore technology to separately isolate HER2 and CD24 expressing extracellular vesicles (EVs) and measured their miRNA cargo using next-generation sequencing. We evaluated the performance of EV-miRNA biomarkers for classifying malignancy and applied LASSO classification to identify a panel of four complementary EV miRNA biomarkers that we validated by qPCR.</p><p><strong>Results: </strong>We identified 19 differentially enriched miRNA from HER2+ EVs and 11 differentially enriched miRNA from CD24+ EVs of women with malignant lesions compared to benign lesions. We observed individual miRNA with an AUC of up to 0.87 for miR-340-5p from HER2+ EVs and 0.75 for miR-223-3p from CD24+ EVs. LASSO classification selected a panel of four complementary EV miRNA for classifying breast cancer: miR-340-5p (HER2+ EVs), miR-598-3p (CD24+), miR-15b-5p (HER2+), and miR-126-3p (CD24+).</p><p><strong>Conclusions: </strong>HER2+ and CD24+ EV subpopulations contain complementary biomarkers suitable for validation in larger studies that can accurately detect early-stage breast cancer among women with BI-RADS category 4 breast lesions.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"27 1","pages":"90"},"PeriodicalIF":7.4,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12096773/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144129290","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":"Impact of germline BRCA1/2 mutations on response to neoadjuvant systemic therapy and prognosis in breast cancer: a propensity score matched cohort study.","authors":"Hyunyou Kim, Jung Whan Chun, Jinha Hwang, Seung Gyu Yun, Jinseob Kim, Seung Pil Jung, Hyeong-Gon Moon, Eun-Shin Lee, Wonshik Han","doi":"10.1186/s13058-025-02041-6","DOIUrl":"10.1186/s13058-025-02041-6","url":null,"abstract":"<p><strong>Background: </strong>We investigated whether germline BRCA1/2 pathogenic variants (PVs) influence treatment response and survival outcomes in breast cancer patients treated with neoadjuvant chemotherapy (NCT). Using propensity score matching (PSM) to control for variations in treatment and clinicopathological characteristics, this study aimed to evaluate the influence of BRCA1/2 mutations on prognosis and treatment efficacy, providing insights for optimizing therapeutic strategies and improving patient outcomes.</p><p><strong>Methods: </strong>We conducted a retrospective cohort study using data from two institutions. The study analyzed breast cancer patients who underwent germline BRCA1/2 testing and received NCT followed by curative resection and standard adjuvant therapy from January 2001 to January 2019. PSM was used to balance confounding variables.</p><p><strong>Results: </strong>Among 411 patients included, 86 have BRCA1/2 mutations. After matching, BRCA1/2 PV carriers had a higher pCR rate (40.0%) compared to wild-type patients (26.5%, OR = 1.85, 95% CI: 1.07-3.22, P = 0.029). They also exhibited a significantly lower 5-year DM rate (4.7% vs. 18.2%, OR = 0.22, 95% CI: 0.08-0.65, P = 0.006). Among pCR patients, outcomes were excellent regardless of BRCA1/2 status. For non-pCR patients, BRCA1/2 PV carriers had better DMFS (hazard ratio (HR) = 0.27, 95% confidence interval (CI) = 0.09-0.81, P = 0.02), though overall survival differences were not significant (HR = 0.47, 95% CI = 0.15-1.47, P = 0.197).</p><p><strong>Conclusions and relevance: </strong>Germline BRCA1/2 mutations are associated with higher pCR rates and improved DMFS in breast cancer patients treated with NCT. These findings emphasize the enhanced chemosensitivity of BRCA-associated tumors and the importance of genetic testing in treatment planning. Further research is needed to validate these findings and optimize treatment strategies.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"27 1","pages":"89"},"PeriodicalIF":7.4,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12096599/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144129324","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":"Docosahexaenoic acid (DHA) supplementation attenuates changes in the concentration, phenotype, and response of immune peripheral blood cells in breast cancer patients undergoing neoadjuvant therapy. Secondary findings from the DHA-WIN trial.","authors":"Jaqueline Munhoz, Marnie Newell, Susan Goruk, Sunita Ghosh, Dhruvesh Patel, Anil Abraham Joy, Gilbert Bigras, Vera Mazurak, Kerry S Courneya, Denise G Hemmings, Catherine J Field","doi":"10.1186/s13058-025-02048-z","DOIUrl":"10.1186/s13058-025-02048-z","url":null,"abstract":"<p><strong>Background: </strong>Breast cancer neoadjuvant therapy may negatively impact the immune system. As a secondary outcome of the docosahexaenoic acid (DHA) for women with breast cancer in the neoadjuvant setting (DHA-WIN trial), we sought to assess the effects of an intervention with DHA on parameters of immune function of women undergoing neoadjuvant therapy.</p><p><strong>Methods: </strong>Women with early-stage breast cancer in the neoadjuvant setting were recruited for the DHA-WIN trial and randomly assigned to receive either 4.4 g/day of DHA or a placebo for 18 weeks in conjunction with their neoadjuvant chemotherapy for breast cancer. Venous blood was collected to isolate peripheral blood mononuclear cells. Immune parameters were assessed by measuring white blood cell concentration, flow cytometry, and cytokines concentration after mitogen-stimulated immune response.</p><p><strong>Results: </strong>In the placebo group the proportion of T cells (CD3 +), and functionally active monocytes (CD14 + HLA-DR +) was reduced at the last cycle of chemotherapy (15 weeks) but remained constant in the DHA group (P interaction < 0.05). The neutrophil-to-lymphocyte ratio (NLR) was maintained in the DHA group but increased in the placebo at the end of chemotherapy (P-interaction = 0.02). An increase in this ratio was associated with lower chance of achieving pathological complete response (OR = 0.32, 95% CI [0.14,0.16], P = 0.01). After 15 weeks of therapy, the DHA-supplemented group had higher concentrations of stimulated cytokines IL-4, IL-10, and the T helper type 1 cytokine IFN-γ after phytohemagglutinin (PHA) challenge, and higher concentrations of TNF-α and IFN-γ cytokines after lipopolysaccharide exposure (P < 0.05).</p><p><strong>Conclusion: </strong>Supplementing DHA during breast cancer neoadjuvant chemotherapy improved systemic immune function by attenuating changes in blood cell concentrations, preventing depletion of immune cells, and enhancing ex vivo cytokine secretion after stimulation.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"27 1","pages":"91"},"PeriodicalIF":7.4,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12100857/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144129320","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":"Intra-tumoral spatial heterogeneity in breast cancer quantified using high-dimensional protein multiplexing and single cell phenotyping.","authors":"Alison M Cheung, Dan Wang, Mary Anne Quintayo, Yulia Yerofeyeva, Melanie Spears, John M S Bartlett, Lincoln Stein, Jane Bayani, Martin J Yaffe","doi":"10.1186/s13058-025-02038-1","DOIUrl":"10.1186/s13058-025-02038-1","url":null,"abstract":"<p><strong>Background: </strong>Breast cancer is a highly heterogeneous disease where variations of biomarker expression may exist between individual foci of a cancer (intra-tumoral heterogeneity). The extent of variation of biomarker expression in the cancer cells, distribution of cell types in the local tumor microenvironment and their spatial arrangement could impact on diagnosis, treatment planning and subsequent response to treatment.</p><p><strong>Methods: </strong>Using quantitative multiplex immunofluorescence (MxIF) imaging, we assessed the level of variations in biomarker expression levels among individual cells, density of cell cluster groups and spatial arrangement of immune subsets from regions sampled from 38 multi-focal breast cancers that were processed using whole-mount histopathology techniques. Molecular profiling was conducted to determine the intrinsic molecular subtype of each analysed region.</p><p><strong>Results: </strong>A subset of cancers (34.2%) showed intra-tumoral regions with more than one molecular subtype classification. High levels of intra-tumoral variations in biomarker expression levels were observed in the majority of cancers studied, particularly in Luminal A cancers. HER2 expression quantified with MxIF did not correlate well with HER2 gene expression, nor with clinical HER2 scores. Unsupervised clustering revealed the presence of various cell clusters with unique IHC4 protein co-expression patterns and the composition of these clusters were mostly similar among intra-tumoral regions. MxIF with immune markers and image patch analysis classified immune niche phenotypes and the prevalence of each phenotype in breast cancer subtypes was illustrated.</p><p><strong>Conclusions: </strong>Our work illustrates the extent of spatial heterogeneity in biomarker expression and immune phenotypes, and highlights the importance of a comprehensive spatial assessment of the disease for prognosis and treatment planning.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"27 1","pages":"88"},"PeriodicalIF":7.4,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12096620/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144121369","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":"Distribution of age at natural menopause, age at menarche, menstrual cycle length, height and BMI in BRCA1 and BRCA2 pathogenic variant carriers and non-carriers: results from EMBRACE.","authors":"Nasim Mavaddat, Debra Frost, Emily Zhao, Daniel R Barnes, Munaza Ahmed, Julian Barwell, Angela F Brady, Paul Brennan, Hector Conti, Jackie Cook, Harriet Copeland, Rosemarie Davidson, Alan Donaldson, Emma Douglas, David Gallagher, Rachel Hart, Louise Izatt, Zoe Kemp, Fiona Lalloo, Zosia Miedzybrodzka, Patrick J Morrison, Jennie E Murray, Alex Murray, Hannah Musgrave, Claire Searle, Lucy Side, Katie Snape, Vishakha Tripathi, Lisa Walker, Stephanie Archer, D Gareth Evans, Marc Tischkowitz, Antonis C Antoniou, Douglas F Easton","doi":"10.1186/s13058-025-02030-9","DOIUrl":"10.1186/s13058-025-02030-9","url":null,"abstract":"<p><strong>Background: </strong>Carriers of germline pathogenic variants (PVs) in the BRCA1 and BRCA2 genes are at higher risk of developing breast and ovarian cancer than the general population. It is unclear if these PVs influence other breast or ovarian cancer risk factors, including age at menopause (ANM), age at menarche (AAM), menstrual cycle length, BMI or height. There is a biological rationale for associations between BRCA1 and BRCA2 PVs and reproductive traits, for example involving DNA damage and repair mechanisms. The evidence for or against such associations is limited.</p><p><strong>Methods: </strong>We used data on 3,046 BRCA1 and 3,264 BRCA2 PV carriers, and 2,857 non-carrier female relatives of PV carriers from the Epidemiological Study of Familial Breast Cancer (EMBRACE). Associations between ANM and PV carrier status was evaluated using linear regression models allowing for censoring. AAM, menstrual cycle length, BMI, and height in carriers and non-carriers were compared using linear and multinomial logistic regression. Analyses were adjusted for potential confounders, and weighted analyses carried out to account for non-random sampling with respect to cancer status.</p><p><strong>Results: </strong>No statistically significant difference in ANM between carriers and non-carriers was observed in analyses accounting for censoring. Linear regression effect sizes for ANM were -0.002 (95%CI: -0.401, 0.397) and -0.172 (95%CI: -0.531, 0.188), for BRCA1 and BRCA2 PV carriers respectively, compared with non-carrier women. The distributions of AAM, menstrual cycle length and BMI were similar between PV carriers and non-carriers, but BRCA1 PV carriers were slightly taller on average than non-carriers (0.5 cm difference, p = 0.003).</p><p><strong>Conclusion: </strong>Information on the distribution of cancer risk factors in PV carriers is needed for incorporating these factors into multifactorial cancer risk prediction algorithms. Contrary to previous reports, we found no evidence that BRCA1 or BRCA2 PV are associated with hormonal or anthropometric factors, except for a weak association with height. We highlight methodological considerations and data limitations inherent in studies aiming to address this question.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"27 1","pages":"87"},"PeriodicalIF":7.4,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12093752/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144121366","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":"Quantifying tumor morphological complexity based on pretreatment MRI fractal analysis for predicting pathologic complete response and survival in breast cancer: a retrospective, multicenter study.","authors":"Yao Huang, Ying Cao, Huifang Chen, Xiaosong Lan, Sun Tang, Zhitao Zhang, Ting Yin, Xiaoxia Wang, Jiuquan Zhang","doi":"10.1186/s13058-025-02034-5","DOIUrl":"10.1186/s13058-025-02034-5","url":null,"abstract":"<p><strong>Background: </strong>The tumor morphological complexity is closely associated with treatment response and prognosis in patients with breast cancer. However, conveniently quantifiable tumor morphological complexity methods are currently lacking.</p><p><strong>Methods: </strong>Women with breast cancer who underwent NAC and pretreatment MRI were retrospectively enrolled at four centers from May 2010 to April 2023. MRI-based fractal analysis was used to calculate fractal dimensions (FDs), quantifying tumor morphological complexity. Features associated with pCR were identified using multivariable logistic regression analysis, upon which a nomogram model was developed, and assessed by the area under the receiver operating characteristic curve (AUC). Cox proportional hazards analysis was used to identify independent prognostic factors for disease-free survival (DFS) and overall survival (OS) and develop nomogram models.</p><p><strong>Results: </strong>A total of 1109 patients (median age, 49 years [IQR, 43-54 years]) were included. The training, external validation cohort 1, and cohort 2 included 435, 351, and 323 patients, respectively. HR status (odds ratio [OR], 0.234 [0.135, 0.406]; P < 0.001), HER2 status (OR, 3.320 [1.923, 5.729]; P < 0.001), and Global FD (OR, 0.352 [0.261, 0.480]; P < 0.001) were independent predictors of pCR. The nomogram model for predicting pCR achieved AUCs of 0.80 (95% CI: 0.75, 0.86) and 0.74 (95% CI: 0.68, 0.79) in the external validation cohorts. The nomogram model, which integrated global FD and clinicopathological variables can stratify prognosis into low-risk and high-risk groups (log-rank test, DFS: P = 0.04; OS: P < 0.001).</p><p><strong>Conclusions: </strong>Global FD can quantify tumor morphological complexity and the model that combines global FD and clinicopathological variables showed good performance in predicting pCR to NAC and survival in patients with breast cancer.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"27 1","pages":"86"},"PeriodicalIF":7.4,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12090479/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144111744","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":"Correction: Predicting Nottingham grade in breast cancer digital pathology using a foundation model.","authors":"Jun Seo Kim, Jeong Hoon Lee, Yousung Yeon, Doyeon An, Seok Jun Kim, Myung-Giun Noh, Suehyun Lee","doi":"10.1186/s13058-025-02047-0","DOIUrl":"10.1186/s13058-025-02047-0","url":null,"abstract":"","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"27 1","pages":"84"},"PeriodicalIF":7.4,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12087022/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144102929","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":"Erbin interacts with NHERF1 and Ezrin to stabilize a membrane ErbB2 signaling complex in HER2-positive breast cancer.","authors":"Jaekwang Jeong, Kwangmin Yoo, Jongwon Lee, Jae Hun Shin, Jungmin Choi, John Wysolmerski","doi":"10.1186/s13058-025-02025-6","DOIUrl":"10.1186/s13058-025-02025-6","url":null,"abstract":"<p><p>Approximately 20% of breast cancers overexpress ErbB2/HER2/Neu, a receptor tyrosine kinase. Our previous studies demonstrated that HER2 interacts with the calcium pump, PMCA2, and the scaffolding molecules, NHERF1 and Ezrin to stabilize HER2/HSP90 interactions and contribute to the retention of active HER2 at the plasma membrane. In the normal mammary epithelium where apical/basal polarity is tightly regulated by junctional proteins, HER2 is expressed at low levels in the basolateral membrane and interacts with the LAP family member, Erbin, whereas PMCA2, NHERF1, and Ezrin localize to the apical membrane. Here, we show that loss of apical membrane polarity in hyperplastic lesions of MMTV-Neu mammary glands or in human DCIS leads to intermixing of these molecules and allows Erbin to interact with NHERF1, Ezrin and HER2 initially within the basolateral membrane and then more diffusely throughout the plasma membrane. In SKBR3 cells, Erbin interacts with NHERF1, Ezrin and HER2 in actin-rich membrane protrusions that we have previously described to be sites of active HER2 signaling. Knockdown of Erbin in these cells reduced HER2 signaling by disrupting the formation of a HER2/NHERF1/Ezrin/HSP90 protein complex in the membrane protrusions. Furthermore, inhibition of Ezrin or knock-down of NHERF1 expression disrupted the ability of Erbin to interact with HER2. Taken together, our data suggest that Erbin supports HER2 stability, HER2 membrane retention and HER2 transforming ability by interacting with Ezrin and NHERF1 to maintain a multi-protein signaling complex necessary for HER2-mediated transformation.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"27 1","pages":"85"},"PeriodicalIF":7.4,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12090624/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144102943","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":"Mammographic density by time and breast: a retrospective cohort study from BreastScreen Norway.","authors":"Nataliia Moshina, Jonas Gjesvik, Tone Hovda, Henrik W Koch, Heinrich A Backmann, Solveig Hofvind","doi":"10.1186/s13058-025-02037-2","DOIUrl":"10.1186/s13058-025-02037-2","url":null,"abstract":"<p><strong>Background: </strong>Mammographic density is known to decrease over time in postmenopausal women. Longitudinal changes in mammographic density prior to breast cancer diagnosis have been widely discussed and less density reduction has been observed for breast developing versus not developing cancer. We aimed to verify these findings among participants of BreastScreen Norway.</p><p><strong>Methods: </strong>In this retrospective cohort study, data from 78,182 women aged 50-69 years who attended three consecutive screening rounds between 2007 and 2020 were included. Among those women, 970 were diagnosed with screen-detected and 308 with interval cancer. Mammographic density data was obtained from an automated software and included absolute (cm³) and percent (%) dense volume for each breast and for each woman, per examination. A linear mixed-effects regression model estimating differences in density between the breast developing and not developing cancer was applied to evaluate longitudinal changes, separately for absolute and percent dense volume. The model was adjusted for age at first screening examination, breast volume, follow-up time, history of benign breast disease, body mass index, family history, hormone therapy, use of alcohol and smoking. Results were presented as linear regression coefficient estimates with 95% confidence intervals (CI).</p><p><strong>Results: </strong>Mean age at the third screening examination for women without breast cancer was 62.5 (standard deviation, SD: 5.1) years, while mean age at diagnosis was 62.3 (SD: 4.4) years for women with screen-detected cancer and 61.9 (SD: 4.8) years for women with interval cancer. In our model, absolute and percent dense volume decreased with follow-up time, estimate=-0.010 (95%CI -0.010; -0.009) and estimate=-0.013 (95%CI -0.014; -0.013), respectively, indicating the overall negative effect of time on mammographic density. The interaction between time and development of breast cancer was positive for absolute and percent dense volume, estimate = 0.009 (95%CI 0.004; 0.014) for both, which implied that mammographic density in breasts developing cancer was stable or slightly decreasing.</p><p><strong>Conclusions: </strong>Less reduction in longitudinally assessed mammographic density was observed for breasts developing versus not developing cancer in our study. This difference might be used for more precise 4-6 years breast cancer risk prediction and screening personalization.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"27 1","pages":"83"},"PeriodicalIF":7.4,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12083168/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144086952","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":"CD105⁺ fibroblasts support an immunosuppressive niche in women at high risk of breast cancer initiation.","authors":"Eric G Carlson, Jennifer C Lopez, Yukiko Yamaguchi, Jackson Gibson, Saul J Priceman, Mark A LaBarge","doi":"10.1186/s13058-025-02040-7","DOIUrl":"10.1186/s13058-025-02040-7","url":null,"abstract":"<p><strong>Background: </strong>Aging is the greatest risk factor for breast cancer, and although epithelial cells are the source of carcinomas, epithelial changes alone do not fully explain cancer susceptibility. Fibroblasts and macrophages are key stromal constituents around the cells of origin for cancer in breast tissue. With age, macrophages surrounding terminal ductal lobular units (TDLUs) become increasingly immunosuppressive. CD105⁺ fibroblasts intercalate within TDLUs, drive luminal differentiation, and give rise to immunosuppressive cancer-associated fibroblasts in other tissues. We propose that differences in fibroblasts are a crucial component of the stroma that shapes cancer susceptibility.</p><p><strong>Methods: </strong>Primary peri-epithelial fibroblast cultures were established from prophylactic and reduction mammoplasties from 30 women ranging in age from 16 to 70 years and from BRCA1 mutation carriers. Growth characteristics, transcriptional profiles, differentiation potential, and secreted proteins were profiled for fibroblast subtypes from diverse donors. Co-cultures with fibroblasts, macrophages, and T cells were used to ascertain the functional role played by CD105⁺ fibroblasts in immune cell modulation.</p><p><strong>Results: </strong>We found that peri-epithelial CD105⁺ fibroblasts are enriched in older women as well as women who carry BRCA1 mutations. These CD105⁺ fibroblasts exhibit robust adipogenesis and secrete factors related to macrophage polarization. Macrophages cocultured with fibroblasts better maintain or enhance polarization states than media alone. CD105⁺ fibroblasts increased expression of immunosuppressive macrophage genes. CD105⁺ fibroblasts supported anti-inflammatory macrophage-mediated suppression of T cell proliferation, whereas CD105^- fibroblasts significantly reduced the suppressive effect of anti-inflammatory macrophages on T cell proliferation.</p><p><strong>Conclusions: </strong>Establishment of a coculture system to dissect the molecular circuits between CD105⁺ fibroblasts and macrophages that drive immunosuppressive macrophage polarization has broad utility in understanding mammary gland development and events that precede cancer initiation. CD105⁺ fibroblasts and macrophages may coordinate to suppress immunosurveillance and increase breast cancer susceptibility.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"27 1","pages":"81"},"PeriodicalIF":7.4,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12079957/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144081442","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}