Breast Cancer Research最新文献

{"title":"Analysis of ductal carcinoma in situ by self-reported race reveals molecular differences related to outcome.","authors":"Siri H Strand, Kathleen E Houlahan, Vernal Branch, Thomas Lynch, Belén Rivero-Guitiérrez, Bryan Harmon, Fergus Couch, Kristalyn Gallagher, Mark Kilgore, Shi Wei, Angela DeMichele, Tari King, Priscilla McAuliffe, Christina Curtis, Kouros Owzar, Jeffrey R Marks, Graham A Colditz, E Shelley Hwang, Robert B West","doi":"10.1186/s13058-024-01885-8","DOIUrl":"10.1186/s13058-024-01885-8","url":null,"abstract":"<p><strong>Background: </strong>Ductal carcinoma in situ (DCIS) is a non-obligate precursor to invasive breast cancer (IBC). Studies have indicated differences in DCIS outcome based on race or ethnicity, but molecular differences have not been investigated.</p><p><strong>Methods: </strong>We examined the molecular profile of DCIS by self-reported race (SRR) and outcome groups in Black (n = 99) and White (n = 191) women in a large DCIS case-control cohort study with longitudinal follow up.</p><p><strong>Results: </strong>Gene expression and pathway analyses suggested that different genes and pathways are involved in diagnosis and ipsilateral breast outcome (DCIS or IBC) after DCIS treatment in White versus Black women. We identified differences in ER and HER2 expression, tumor microenvironment composition, and copy number variations by SRR and outcome groups.</p><p><strong>Conclusions: </strong>Our results suggest that different molecular mechanisms drive initiation and subsequent ipsilateral breast events in Black versus White women.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"26 1","pages":"127"},"PeriodicalIF":7.4,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11367816/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142120969","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":"Elevated expression of Aurora-A/AURKA in breast cancer associates with younger age and aggressive features.","authors":"L M Ingebriktsen, R O C Humlevik, A A Svanøe, A K M Sæle, I Winge, K Toska, M B Kalvenes, B Davidsen, A Heie, G Knutsvik, C Askeland, I M Stefansson, E A Hoivik, L A Akslen, E Wik","doi":"10.1186/s13058-024-01882-x","DOIUrl":"10.1186/s13058-024-01882-x","url":null,"abstract":"<p><strong>Background and objective: </strong>Aurora kinase A (AURKA) is reported to be overexpressed in breast cancer. In addition to its role in regulating cell cycle and mitosis, studies have reported AURKA involvements in oncogenic signaling in suppressing BRCA1 and BRCA2. We aimed to characterize AURKA protein and mRNA expression in a breast cancer cohort of the young, investigating its relation to clinico-pathologic features and survival, and exploring age-related AURKA-associated biological processes.</p><p><strong>Methods: </strong>Aurora kinase A immunohistochemical staining was performed on tissue microarrays of primary tumors from an in-house breast cancer cohort (n = 355) with information on clinico-pathologic data, molecular markers, and long and complete follow-up. A subset of the in-house cohort (n = 127) was studied by the NanoString Breast Cancer 360 expression panel for exploration of mRNA expression. METABRIC cohorts < 50 years at breast cancer diagnosis (n = 368) were investigated for differentially expressed genes and enriched gene sets in AURKA mRNA high tumors stratified by age. Differentially expressed genes and gene sets were investigated using network analyses and g:Profiler.</p><p><strong>Results: </strong>High Aurora kinase A protein expression associated with aggressive clinico-pathologic features, a basal-like subtype, and high risk of recurrence score. These patterns were confirmed using mRNA data. High AURKA gene expression demonstrated independent prognostic value when adjusted for traditional clinico-pathologic features and molecular subtypes. Notably, high AURKA expression significantly associated with reduced disease-specific survival within patients below 50 years, also within the luminal A subtype. Tumors of high AURKA expression showed gene expression patterns reflecting increased DNA damage activation and higher BRCAness score.</p><p><strong>Conclusions: </strong>Our findings indicate higher AURKA expression in young breast cancer, and associations between high Aurora-A/AURKA and aggressive tumor features, including higher tumor cell proliferation, and shorter survival, in the young. Our findings point to AURKA as a marker for increased DNA damage and DNA repair deficiency and suggest AURKA as a biomarker of clinical relevance in young breast cancer.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"26 1","pages":"126"},"PeriodicalIF":7.4,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11360479/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142094098","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":"Systematic assessment of HER2 status in ductal carcinoma in situ of the breast: a perspective on the potential clinical relevance.","authors":"Mieke R Van Bockstal, Jelle Wesseling, Ester H Lips, Marjolein Smidt, Christine Galant, Carolien H M van Deurzen","doi":"10.1186/s13058-024-01875-w","DOIUrl":"10.1186/s13058-024-01875-w","url":null,"abstract":"<p><p>In many countries, hormone receptor status assessment of ductal carcinoma in situ (DCIS) is routinely performed, as hormone receptor-positive DCIS patients are eligible for adjuvant anti-hormonal treatment, aiming to reduce the ipsilateral and contralateral breast cancer risk. Although HER2 gene amplification and its associated HER2 protein overexpression constitute a major prognostic and predictive marker in invasive breast carcinoma, its use in the diagnosis and treatment of DCIS is less straightforward. HER2 immunohistochemistry is not routinely performed yet, as the role of HER2-positivity in DCIS biology is unclear. Nonetheless, recent data challenge this practice. Here, we discuss the value of routine HER2 assessment for DCIS. HER2-positivity correlates strongly with DCIS grade: around four in five HER2-positive DCIS show high grade atypia. As morphological DCIS grading is prone to interobserver variability, HER2 immunohistochemistry could render grading more robust. Several studies showed an association between HER2-positive DCIS and ipsilateral recurrence risk, albeit currently unclear whether this is for overall, in situ or invasive recurrence. HER2-positive DCIS tends to be larger, with a higher risk of involved surgical margins. HER2-positive DCIS patients benefit more from adjuvant radiotherapy: it substantially decreases the local recurrence risk after lumpectomy, without impact on overall survival. HER2-positivity in pure biopsy-diagnosed DCIS is associated with increased upstaging to invasive carcinoma after surgery. HER2 immunohistochemistry on preoperative biopsies might therefore provide useful information to surgeons, favoring wider excisions. The time seems right to consider DCIS subtype-dependent treatment, comprising appropriate local treatment for HER2-positive DCIS patients and de-escalation for hormone receptor-positive, HER2-negative DCIS patients.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"26 1","pages":"125"},"PeriodicalIF":7.4,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11348742/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142082411","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":"Weakly-supervised deep learning models enable HER2-low prediction from H &E stained slides.","authors":"Renan Valieris, Luan Martins, Alexandre Defelicibus, Adriana Passos Bueno, Cynthia Aparecida Bueno de Toledo Osorio, Dirce Carraro, Emmanuel Dias-Neto, Rafael A Rosales, Jose Marcio Barros de Figueiredo, Israel Tojal da Silva","doi":"10.1186/s13058-024-01863-0","DOIUrl":"10.1186/s13058-024-01863-0","url":null,"abstract":"<p><strong>Background: </strong>Human epidermal growth factor receptor 2 (HER2)-low breast cancer has emerged as a new subtype of tumor, for which novel antibody-drug conjugates have shown beneficial effects. Assessment of HER2 requires several immunohistochemistry tests with an additional in situ hybridization test if a case is classified as HER2 2+. Therefore, novel cost-effective methods to speed up the HER2 assessment are highly desirable.</p><p><strong>Methods: </strong>We used a self-supervised attention-based weakly supervised method to predict HER2-low directly from 1437 histopathological images from 1351 breast cancer patients. We built six distinct models to explore the ability of classifiers to distinguish between the HER2-negative, HER2-low, and HER2-high classes in different scenarios. The attention-based model was used to comprehend the decision-making process aimed at relevant tissue regions.</p><p><strong>Results: </strong>Our results indicate that the effectiveness of classification models hinges on the consistency and dependability of assay-based tests for HER2, as the outcomes from these tests are utilized as the baseline truth for training our models. Through the use of explainable AI, we reveal histologic patterns associated with the HER2 subtypes.</p><p><strong>Conclusion: </strong>Our findings offer a demonstration of how deep learning technologies can be applied to identify HER2 subgroup statuses, potentially enriching the toolkit available for clinical decision-making in oncology.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"26 1","pages":"124"},"PeriodicalIF":7.4,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11331614/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142005685","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":"Validation of an AI-based solution for breast cancer risk stratification using routine digital histopathology images.","authors":"Abhinav Sharma, Sandy Kang Lövgren, Kajsa Ledesma Eriksson, Yinxi Wang, Stephanie Robertson, Johan Hartman, Mattias Rantalainen","doi":"10.1186/s13058-024-01879-6","DOIUrl":"10.1186/s13058-024-01879-6","url":null,"abstract":"<p><strong>Background: </strong>Stratipath Breast is a CE-IVD marked artificial intelligence-based solution for prognostic risk stratification of breast cancer patients into high- and low-risk groups, using haematoxylin and eosin (H&E)-stained histopathology whole slide images (WSIs). In this validation study, we assessed the prognostic performance of Stratipath Breast in two independent breast cancer cohorts.</p><p><strong>Methods: </strong>This retrospective multi-site validation study included 2719 patients with primary breast cancer from two Swedish hospitals. The Stratipath Breast tool was applied to stratify patients based on digitised WSIs of the diagnostic H&E-stained tissue sections from surgically resected tumours. The prognostic performance was evaluated using time-to-event analysis by multivariable Cox Proportional Hazards analysis with progression-free survival (PFS) as the primary endpoint.</p><p><strong>Results: </strong>In the clinically relevant oestrogen receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative patient subgroup, the estimated hazard ratio (HR) associated with PFS between low- and high-risk groups was 2.76 (95% CI: 1.63-4.66, p-value < 0.001) after adjusting for established risk factors. In the ER+/HER2- Nottingham histological grade (NHG) 2 subgroup, the HR was 2.20 (95% CI: 1.22-3.98, p-value = 0.009) between low- and high-risk groups.</p><p><strong>Conclusion: </strong>The results indicate an independent prognostic value of Stratipath Breast among all breast cancer patients, as well as in the clinically relevant ER+/HER2- subgroup and the NHG2/ER+/HER2- subgroup. Improved risk stratification of intermediate-risk ER+/HER2- breast cancers provides information relevant for treatment decisions of adjuvant chemotherapy and has the potential to reduce both under- and overtreatment. Image-based risk stratification provides the added benefit of short lead times and substantially lower cost compared to molecular diagnostics and therefore has the potential to reach broader patient groups.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"26 1","pages":"123"},"PeriodicalIF":7.4,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11323658/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141983718","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 SEMA3F-NRP1/NRP2 axis is a key factor in the acquisition of invasive traits in in situ breast ductal carcinoma.","authors":"Núria Moragas, Patricia Fernandez-Nogueira, Leire Recalde-Percaz, Jamie L Inman, Anna López-Plana, Helga Bergholtz, Aleix Noguera-Castells, Pedro J Del Burgo, Xieng Chen, Therese Sorlie, Pere Gascón, Paloma Bragado, Mina Bissell, Neus Carbó, Gemma Fuster","doi":"10.1186/s13058-024-01871-0","DOIUrl":"10.1186/s13058-024-01871-0","url":null,"abstract":"<p><strong>Background: </strong>A better understanding of ductal carcinoma in situ (DCIS) is urgently needed to identify these preinvasive lesions as distinct clinical entities. Semaphorin 3F (SEMA3F) is a soluble axonal guidance molecule, and its coreceptors Neuropilin 1 (NRP1) and NRP2 are strongly expressed in invasive epithelial BC cells.</p><p><strong>Methods: </strong>We utilized two cell line models to represent the progression from a healthy state to the mild-aggressive or ductal carcinoma in situ (DCIS) stage and, ultimately, to invasive cell lines. Additionally, we employed in vivo models and conducted analyses on patient databases to ensure the translational relevance of our results.</p><p><strong>Results: </strong>We revealed SEMA3F as a promoter of invasion during the DCIS-to-invasive ductal carcinoma transition in breast cancer (BC) through the action of NRP1 and NRP2. In epithelial cells, SEMA3F activates epithelialmesenchymal transition, whereas it promotes extracellular matrix degradation and basal membrane and myoepithelial cell layer breakdown.</p><p><strong>Conclusions: </strong>Together with our patient database data, these proof-of-concept results reveal new SEMA3F-mediated mechanisms occurring in the most common preinvasive BC lesion, DCIS, and represent potent and direct activation of its transition to invasion. Moreover, and of clinical and therapeutic relevance, the effects of SEMA3F can be blocked directly through its coreceptors, thus preventing invasion and keeping DCIS lesions in the preinvasive state.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"26 1","pages":"122"},"PeriodicalIF":7.4,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11320849/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141977014","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":"Association of Life's Essential 8 cardiovascular health with breast cancer incidence and mortality according to genetic susceptibility of breast cancer: a prospective cohort study.","authors":"Yan Zhao, Yang Song, Xiangmin Li, Ayao Guo","doi":"10.1186/s13058-024-01877-8","DOIUrl":"10.1186/s13058-024-01877-8","url":null,"abstract":"<p><strong>Background: </strong>Accumulating evidence suggests that cardiovascular diseases and breast cancer share a number of common risk factors, however, evidence on the association between cardiovascular health (CVH) and breast cancer is limited. The present study aimed to assess the association of CVH, defined by Life's Essential 8 (LE8) and genetic risk with breast cancer incidence and mortality among premenopausal and postmenopausal women.</p><p><strong>Methods: </strong>We used data from the UK Biobank and conducted the multivariate Cox proportional-hazards models to examine associations of LE8 score and genetic risk with breast cancer incidence and mortality. Date on LE8 score was collected between 2006 and 2010 and composed of eight components, including behavioral metrics (diet, tobacco or nicotine exposure, physical activity, and sleep health), and biological metrics (body mass index, blood lipids, blood glucose, and blood pressure). The polygenic risk score (PRS) was calculated as the sum of effect sizes of individual genetic variants multiplied by the allele dosage.</p><p><strong>Results: </strong>A total of 150,566 premenopausal and postmenopausal women were included. Compared to postmenopausal women with low LE8 score, those with high LE8 score were associated with 22% lower risk of breast cancer incidence (HR: 0.78, 95% CI: 0.70-0.87) and 43% lower risk of breast cancer mortality (HR: 0.57, 95% CI: 0.36-0.90). By contrast, we did not observe the significant association among premenopausal women. Further analyses stratified by PRS categories showed that high LE8 score was associated with 28% and 71% decreased risk of breast cancer incidence (HR: 0.72, 95% CI: 0.60-0.87) and mortality (HR: 0.29, 95% CI: 0.10-0.83) compared to low LE8 score among high genetic risk groups, but no significant associations were found among low genetic risk groups. Furthermore, compared with postmenopausal women with high LE8 score and low genetic risk, those with low LE8 score and high genetic risk were associated with increased risk of breast cancer incidence (HR: 6.26, 95% CI: 4.43-8.84).</p><p><strong>Conclusions: </strong>The present study suggests that better CVH is a protective factor for both breast cancer incidence and mortality among postmenopausal women. Moreover, the risk of developing breast cancer caused by high genetic susceptibility could be largely offset by better CVH.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"26 1","pages":"121"},"PeriodicalIF":7.4,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11311885/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141908094","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":"Micrometastases in axillary lymph nodes in breast cancer, post-neoadjuvant systemic therapy.","authors":"Janghee Lee, Seho Park, Soong June Bae, Junghwan Ji, Dooreh Kim, Jee Ye Kim, Hyung Seok Park, Sung Gwe Ahn, Seung Il Kim, Byeong-Woo Park, Joon Jeong","doi":"10.1186/s13058-024-01874-x","DOIUrl":"10.1186/s13058-024-01874-x","url":null,"abstract":"<p><strong>Introduction: </strong>The significance of minimal residual axillary disease, specifically micrometastases, following neoadjuvant systemic therapy (NST) remains largely unexplored. Our study aimed to elucidate the prognostic implications of micrometastases in axillary and sentinel lymph nodes following NST.</p><p><strong>Methods: </strong>This retrospective study analyzed primary breast cancer patients who underwent surgery after NST from September 2006 through February 2018. All patients received axillary lymph node dissection (ALND), either with or without sentinel lymph node biopsy. Recurrence-free survival (RFS)-associated variables were identified using a multivariate Cox proportional hazard model.</p><p><strong>Results: </strong>Of the 978 patients examined, 438 (44.8%) exhibited no pathologic lymph node involvement (ypN0) after NST, while 89 (9.1%) had micrometastases (ypN1mi) and 451 (46.7%) had macrometastases (ypN+). Notably, 51.1% of the patients with sentinel lymph node micrometastases (SLNmi) had additional metastases, nearly triple that of SLN-negative patients (P < 0.001), and 29.8% of SLNmi patients were upstaged with the ALND. Although ypN1mi was not associated with RFS in patients post-NST (HR, 1.02; 95% CI, 0.42-2.49; P = 0.958), SLNmi patients experienced significantly worse RFS compared to SLN-negative patients (hazard ratio [HR], 2.23; 95% confidence intervals [CI], 1.12-4.46; P = 0.023). Additional metastases in SLNmi were more prevalent in patients with larger residual breast disease greater than 20 mm, HR-positive/HER2-negative subtype, and low Ki-67 LI (< 14%).</p><p><strong>Conclusions: </strong>SLNmi is a negative prognostic factor significantly associated with additional non-SLN metastases, while ypN1mi does not influence the prognosis compared to ypN0. Hence, additional ALND may be warranted to confirm axillary nodal status in patients with SLNmi.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"26 1","pages":"120"},"PeriodicalIF":7.4,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11293213/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141861372","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":"Development of a humanized anti-FABP4 monoclonal antibody for potential treatment of breast cancer.","authors":"Jiaqing Hao, Rong Jin, Yanmei Yi, Xingshan Jiang, Jianyu Yu, Zhen Xu, Nicholas J Schnicker, Michael S Chimenti, Sonia L Sugg, Bing Li","doi":"10.1186/s13058-024-01873-y","DOIUrl":"10.1186/s13058-024-01873-y","url":null,"abstract":"<p><strong>Background: </strong>Breast cancer is the most common cancer in women diagnosed in the U.S. and worldwide. Obesity increases breast cancer risk without clear underlying molecular mechanisms. Our studies demonstrate that circulating adipose fatty acid binding protein (A-FABP, or FABP4) links obesity-induced dysregulated lipid metabolism and breast cancer risk, thus potentially offering a new target for breast cancer treatment.</p><p><strong>Methods: </strong>We immunized FABP4 knockout mice with recombinant human FABP4 and screened hybridoma clones with specific binding to FABP4. The potential effects of antibodies on breast cancer cells in vitro were evaluated using migration, invasion, and limiting dilution assays. Tumor progression in vivo was evaluated in various types of tumorigenesis models including C57BL/6 mice, Balb/c mice, and SCID mice. The phenotype and function of immune cells in tumor microenvironment were characterized with multi-color flow cytometry. Tumor stemness was detected by ALDH assays. To characterize antigen-antibody binding capacity, we determined the dissociation constant of selected anti-FABP4 antibodies via surface plasmon resonance. Further analyses in tumor tissue were performed using 10X Genomics Visium spatial single cell technology.</p><p><strong>Results: </strong>Herein, we report the generation of humanized monoclonal antibodies blocking FABP4 activity for breast cancer treatment in mouse models. One clone, named 12G2, which significantly reduced circulating levels of FABP4 and inhibited mammary tumor growth, was selected for further characterization. After confirming the therapeutic efficacy of the chimeric 12G2 monoclonal antibody consisting of mouse variable regions and human IgG1 constant regions, 16 humanized 12G2 monoclonal antibody variants were generated by grafting its complementary determining regions to selected human germline sequences. Humanized V9 monoclonal antibody showed consistent results in inhibiting mammary tumor growth and metastasis by affecting tumor cell mitochondrial metabolism.</p><p><strong>Conclusions: </strong>Our current evidence suggests that targeting FABP4 with humanized monoclonal antibodies may represent a novel strategy for the treatment of breast cancer and possibly other obesity- associated diseases.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"26 1","pages":"119"},"PeriodicalIF":7.4,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11270797/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141762007","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":"Genomic profiling and comparative analysis of male versus female metastatic breast cancer across subtypes.","authors":"Arun Kadamkulam Syriac, Nitish Singh Nandu, Allison Clark, Mehrad Tavallai, Dexter X Jin, Ethan Sokol, Kimberly McGregor, Jeffrey S Ross, Natalie Danziger, Jose Pablo Leone","doi":"10.1186/s13058-024-01872-z","DOIUrl":"10.1186/s13058-024-01872-z","url":null,"abstract":"<p><strong>Background: </strong>Male breast cancer (MaBC) has limited data on genomic alterations. We aimed to comprehensively describe and compare MaBC's genomics with female breast cancer's (FBC) across subtypes.</p><p><strong>Methods: </strong>Using genomic data from Foundation Medicine, we categorized 253 MaBC into estrogen receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative (n = 210), ER-positive/HER2-positive (n = 22) and triple-negative (n = 20). One ER-negative/HER2-positive case was excluded due to n-of-1. The genomics of the final MaBC cohort (n = 252) were compared to a FBC cohort (n = 2708) stratified by molecular subtype, with adjusted p-values. In the overall MaBC and FBC cohorts, we compared mutational prevalence in cancer susceptibility genes (CSG) (ATM/BRCA1/BRCA2/CHEK2/PALB2).</p><p><strong>Results: </strong>Comparing ER-positive/HER2-negative cases, MaBc had increased alterations in GATA3 (26.2% vs. 15.9%, p = 0.005), BRCA2 (13.8% vs. 5.3%, p < 0.001), MDM2 (13.3% vs. 6.14%, p = 0.004) and CDK4 (7.1% vs. 1.8%, p < 0.001); and decreased frequency of TP53 (11.0% vs. 42.6%, p < 0.001) and ESR1 mutations (5.7% vs. 14.6%, p < 0.001). Comparing ER-positive/HER2-positive cases, MaBC had increased short variants in ERBB2 (22.7% vs. 0.6%, p = 0.002), GATA3 (36.3% vs. 6.2%, p = 0.004), and MDM2 (36.3% vs. 4.9%, p = 0.002); decreased frequency of TP53 alterations was seen in MaBC versus FBC (9.1% vs. 61.7%, p < 0.001). Within triple-negative cases, MaBC had decreased alterations in TP53 compared to FBC (25.0% vs. 84.4%, p < 0.001). MaBC had higher frequency of CSG variants than FBC (22.6% vs. 14.6%, p < 0.05), with increased BRCA mutations in MaBC (14.6% vs. 9.1%, p < 0.05).</p><p><strong>Conclusions: </strong>Although MaBC and FBC share some common alterations, our study revealed several important differences relevant to tumor biology and implications for targeted therapies.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"26 1","pages":"118"},"PeriodicalIF":7.4,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11267671/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141762008","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}