Breast Cancer Research最新文献

{"title":"Correction: a phase 1b study of zilovertamab in combination with paclitaxel for locally advanced/unresectable or metastatic HER2-negative breast cancer.","authors":"Rebecca A Shatsky, Hemali Batra-Sharma, Teresa Helsten, Richard B Schwab, Emily I Pittman, Minya Pu, Elizabeth Weihe, Emanuela M Ghia, Laura Z Rassenti, Alfredo Molinolo, Betty Cabrera, James B Breitmeyer, George F Widhopf Ii, Karen Messer, Catriona Jamieson, Thomas J Kipps, Barbara A Parker","doi":"10.1186/s13058-024-01805-w","DOIUrl":"10.1186/s13058-024-01805-w","url":null,"abstract":"","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":null,"pages":null},"PeriodicalIF":7.4,"publicationDate":"2024-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10938766/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140121176","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":"Breast composition during and after puberty: the Chilean Growth and Obesity Cohort Study.","authors":"Ana Pereira, María Luisa Garmendia, Valeria Leiva, Camila Corvalán, Karin B Michels, John Shepherd","doi":"10.1186/s13058-024-01793-x","DOIUrl":"10.1186/s13058-024-01793-x","url":null,"abstract":"<p><strong>Background: </strong>Breast density (BD) is a strong risk factor for breast cancer. Little is known about how BD develops during puberty. Understanding BD trajectories during puberty and its determinants could be crucial for promoting preventive actions against breast cancer (BC) at early ages. The objective of this research is to characterize % fibroglandular volume (%FGV), absolute fibroglandular volume (AFGV), and breast volume (BV) at different breast Tanner stages until 4-year post menarche in a Latino cohort and to assess determinants of high %FGV and AFGV during puberty and in a fully mature breast.</p><p><strong>Methods: </strong>This is a longitudinal follow-up of 509 girls from low-middle socioeconomic status of the Southeast area of Santiago, recruited at a mean age of 3.5 years. The inclusion criteria were singleton birth born, birthweight between 2500 and 4500 g with no medical or mental disorder. A trained dietitian measured weight and height since 3.5 years old and sexual maturation from 8 years old (breast Tanner stages and age at menarche onset). Using standardized methods, BD was measured using dual-energy X-ray absorptiometry (DXA) in various developmental periods (breast Tanner stage B1 until 4 years after menarche onset).</p><p><strong>Results: </strong>In the 509 girls, we collected 1,442 breast DXA scans; the mean age at Tanner B4 was 11.3 years. %FGV increased across breast Tanner stages and peaked 250 days after menarche. AFGV and BV peaked 2 years after menarche onset. Girls in the highest quartiles of %FGV, AFGV, and BV at Tanner B4 and B5 before menarche onset had the highest values thereafter until 4 years after menarche onset. The most important determinants of %FGV and AFGV variability were BMI z-score (R² = 44%) and time since menarche (R² = 42%), respectively.</p><p><strong>Conclusion: </strong>We characterize the breast development during puberty, a critical window of susceptibility. Although the onset of menarche is a key milestone for breast development, we observed that girls in the highest quartiles of %FGV and AFGV tracked in that group afterwards. Following these participants in adulthood would be of interest to understand the changes in breast composition during this period and its potential link with BC risk.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":null,"pages":null},"PeriodicalIF":7.4,"publicationDate":"2024-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10935788/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140111919","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":"UCHL1 contributes to insensitivity to endocrine therapy in triple-negative breast cancer by deubiquitinating and stabilizing KLF5.","authors":"Juan Li, Yu Liang, Shijie Zhou, Jie Chen, Chihua Wu","doi":"10.1186/s13058-024-01800-1","DOIUrl":"10.1186/s13058-024-01800-1","url":null,"abstract":"<p><strong>Background: </strong>Ubiquitin carboxyl-terminal hydrolase L1 (UCHL1) is a deubiquitinating enzyme that regulates ERα expression in triple-negative cancer (TNBC). This study aimed to explore the deubiquitination substrates of UCHL1 related to endocrine therapeutic responses and the mechanisms of UCHL1 dysregulation in TNBC.</p><p><strong>Methods: </strong>Bioinformatics analysis was conducted using online open databases. TNBC representative MDA-MB-468 and SUM149 cells were used for in vitro and in-vivo studies. Co-immunoprecipitation was used to explore the interaction between UCHL1 and KLF5 and UCHL1-mediated KIF5 deubiquitination. CCK-8, colony formation and animal studies were performed to assess endocrine therapy responses. The regulatory effect of TET1/3 on UCHL1 promoter methylation and transcription was performed by Bisulfite sequencing PCR and ChIP-qPCR.</p><p><strong>Results: </strong>UCHL1 interacts with KLF5 and stabilizes KLF5 by reducing its polyubiquitination and proteasomal degradation. The UCHL1-KLF5 axis collaboratively upregulates EGFR expression while downregulating ESR1 expression at both mRNA and protein levels in TNBC. UCHL1 knockdown slows the proliferation of TNBC cells and sensitizes the tumor cells to Tamoxifen and Fulvestrant. KLF5 overexpression partially reverses these trends. Both TET1 and TET3 can bind to the UCHL1 promoter region, reducing methylation of associated CpG sites and enhancing UCHL1 transcription in TNBC cell lines. Additionally, TET1 and TET3 elevates KLF5 protein level in a UCHL1-dependent manner.</p><p><strong>Conclusion: </strong>UCHL1 plays a pivotal role in TNBC by deubiquitinating and stabilizing KLF5, contributing to endocrine therapy resistance. TET1 and TET3 promote UCHL1 transcription through promoter demethylation and maintain KLF5 protein level in a UCHL1-dependent manner, implying their potential as therapeutic targets in TNBC.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":null,"pages":null},"PeriodicalIF":7.4,"publicationDate":"2024-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10929172/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140102670","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":"Cell morphology best predicts tumorigenicity and metastasis in vivo across multiple TNBC cell lines of different metastatic potential.","authors":"Sydney J Conner, Justinne R Guarin, Thanh T Le, Jackson P Fatherree, Charlotte Kelley, Samantha L Payne, Savannah R Parker, Hanan Bloomer, Crystal Zhang, Kenneth Salhany, Rachel A McGinn, Emily Henrich, Anna Yui, Deepti Srinivasan, Hannah Borges, Madeleine J Oudin","doi":"10.1186/s13058-024-01796-8","DOIUrl":"10.1186/s13058-024-01796-8","url":null,"abstract":"<p><strong>Background: </strong>Metastasis is the leading cause of death in breast cancer patients. For metastasis to occur, tumor cells must invade locally, intravasate, and colonize distant tissues and organs, all steps that require tumor cell migration. The majority of studies on invasion and metastasis rely on human breast cancer cell lines. While it is known that these cells have different properties and abilities for growth and metastasis, the in vitro morphological, proliferative, migratory, and invasive behavior of these cell lines and their correlation to in vivo behavior is poorly understood. Thus, we sought to classify each cell line as poorly or highly metastatic by characterizing tumor growth and metastasis in a murine model of six commonly used human triple-negative breast cancer xenografts, as well as determine which in vitro assays commonly used to study cell motility best predict in vivo metastasis.</p><p><strong>Methods: </strong>We evaluated the liver and lung metastasis of human TNBC cell lines MDA-MB-231, MDA-MB-468, BT549, Hs578T, BT20, and SUM159 in immunocompromised mice. We characterized each cell line's cell morphology, proliferation, and motility in 2D and 3D to determine the variation in these parameters between cell lines.</p><p><strong>Results: </strong>We identified MDA-MB-231, MDA-MB-468, and BT549 cells as highly tumorigenic and metastatic, Hs578T as poorly tumorigenic and metastatic, BT20 as intermediate tumorigenic with poor metastasis to the lungs but highly metastatic to the livers, and SUM159 as intermediate tumorigenic but poorly metastatic to the lungs and livers. We showed that metrics that characterize cell morphology are the most predictive of tumor growth and metastatic potential to the lungs and liver. Further, we found that no single in vitro motility assay in 2D or 3D significantly correlated with metastasis in vivo.</p><p><strong>Conclusions: </strong>Our results provide an important resource for the TNBC research community, identifying the metastatic potential of 6 commonly used cell lines. Our findings also support the use of cell morphological analysis to investigate the metastatic potential and emphasize the need for multiple in vitro motility metrics using multiple cell lines to represent the heterogeneity of metastasis in vivo.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":null,"pages":null},"PeriodicalIF":7.4,"publicationDate":"2024-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10929179/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140102669","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":"Detection of HER2 expression using ^99mTc-NM-02 nanobody in patients with breast cancer: a non-randomized, non-blinded clinical trial.","authors":"Lingzhou Zhao, Yan Xing, Changcun Liu, Shaofei Ma, Wenhua Huang, Zhen Cheng, Jinhua Zhao","doi":"10.1186/s13058-024-01803-y","DOIUrl":"10.1186/s13058-024-01803-y","url":null,"abstract":"<p><strong>Background: </strong>^99mTc radiolabeled nanobody NM-02 (^99mTc-NM-02) is a novel single photon emission computed tomography (SPECT) probe with a high affinity and specificity for human epidermal growth factor receptor 2 (HER2). In this study, a clinical imaging trial was conducted to investigate the relationship between ^99mTc-NM-02 uptake and HER2 expression in patients with breast cancer.</p><p><strong>Methods: </strong>Thirty patients with pathologically confirmed breast cancer were recruited and imaged with both ^99mTc-NM-02 SPECT/computed tomography (CT) and ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography (PET)/CT. According to the treatment conditions before recruitment, patients were divided into two groups, the newly diagnosed group (n = 24) and the treated group (n = 6). The maximal standard uptake value (SUV_max) of ¹⁸F-FDG and SUV_max and mean SUV (SUV_mean) of ^99mTc-NM-02 in the lesions were determined to analyze the relationship with HER2 expression.</p><p><strong>Results: </strong>No meaningful relationship was observed between ¹⁸F-FDG uptake and HER2 expression in 30 patients with breast cancer. ^99mTc-NM-02 uptake was positively correlated with HER2 expression in the newly diagnosed group, but no correlation was observed in the treated group. ^99mTc-NM-02 uptake in HER2-positive lesions was lower in those with effective HER2-targeted therapy compared with the newly diagnosed group. ^99mTc-NM-02 SPECT/CT detected brain and bone metastases of breast cancer with a different imaging pattern from ¹⁸F-FDG PET/CT. ^99mTc-NM-02 showed no non-specific uptake in inflamed tissues and revealed intra- and intertumoral HER2 heterogeneity by SPECT/CT imaging in 9 of the 30 patients with breast cancer.</p><p><strong>Conclusions: </strong>^99mTc-NM-02 SPECT/CT has the potential for visualizing whole-body HER2 overexpression in untreated patients, making it a promising method for HER2 assessment in patients with breast cancer.</p><p><strong>Trial registration: </strong>NCT04674722, Date of registration: December 19, 2020.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":null,"pages":null},"PeriodicalIF":7.4,"publicationDate":"2024-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10924314/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140066030","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 risk analysis of alpelisib-induced hyperglycemia in patients with advanced solid tumors and breast cancer.","authors":"Jordi Rodón, David Demanse, Hope S Rugo, Howard A Burris, Rafael Simó, Azeez Farooki, Melissa F Wellons, Fabrice André, Huilin Hu, Dragica Vuina, Cornelia Quadt, Dejan Juric","doi":"10.1186/s13058-024-01773-1","DOIUrl":"10.1186/s13058-024-01773-1","url":null,"abstract":"<p><strong>Background: </strong>Hyperglycemia is an on-target effect of PI3Kα inhibitors. Early identification and intervention of treatment-induced hyperglycemia is important for improving management of patients receiving a PI3Kα inhibitor like alpelisib. Here, we characterize incidence of grade 3/4 alpelisib-related hyperglycemia, along with time to event, management, and outcomes using a machine learning model.</p><p><strong>Methods: </strong>Data for the risk model were pooled from patients receiving alpelisib ± fulvestrant in the open-label, phase 1 X2101 trial and the randomized, double-blind, phase 3 SOLAR-1 trial. The pooled population (n = 505) included patients with advanced solid tumors (X2101, n = 221) or HR+/HER2- advanced breast cancer (SOLAR-1, n = 284). External validation was performed using BYLieve trial patient data (n = 340). Hyperglycemia incidence and management were analyzed for SOLAR-1.</p><p><strong>Results: </strong>A random forest model identified 5 baseline characteristics most associated with risk of developing grade 3/4 hyperglycemia (fasting plasma glucose, body mass index, HbA_1c, monocytes, age). This model was used to derive a score to classify patients as high or low risk for developing grade 3/4 hyperglycemia. Applying the model to patients treated with alpelisib and fulvestrant in SOLAR-1 showed higher incidence of hyperglycemia (all grade and grade 3/4), increased use of antihyperglycemic medications, and more discontinuations due to hyperglycemia (16.7% vs. 2.6% of discontinuations) in the high- versus low-risk group. Among patients in SOLAR-1 (alpelisib + fulvestrant arm) with PIK3CA mutations, median progression-free survival was similar between the high- and low-risk groups (11.0 vs. 10.9 months). For external validation, the model was applied to the BYLieve trial, for which successful classification into high- and low-risk groups with shorter time to grade 3/4 hyperglycemia in the high-risk group was observed.</p><p><strong>Conclusions: </strong>A risk model using 5 clinically relevant baseline characteristics was able to identify patients at higher or lower probability for developing alpelisib-induced hyperglycemia. Early identification of patients who may be at higher risk for hyperglycemia may improve management (including monitoring and early intervention) and potentially lead to improved outcomes.</p><p><strong>Registration: </strong>ClinicalTrials.gov: NCT01219699 (registration date: October 13, 2010; retrospectively registered), ClinicalTrials.gov: NCT02437318 (registration date: May 7, 2015); ClinicalTrials.gov: NCT03056755 (registration date: February 17, 2017).</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":null,"pages":null},"PeriodicalIF":7.4,"publicationDate":"2024-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10913434/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140029404","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":"Augmented interpretation of HER2, ER, and PR in breast cancer by artificial intelligence analyzer: enhancing interobserver agreement through a reader study of 201 cases.","authors":"Minsun Jung, Seung Geun Song, Soo Ick Cho, Sangwon Shin, Taebum Lee, Wonkyung Jung, Hajin Lee, Jiyoung Park, Sanghoon Song, Gahee Park, Heon Song, Seonwook Park, Jinhee Lee, Mingu Kang, Jongchan Park, Sergio Pereira, Donggeun Yoo, Keunhyung Chung, Siraj M Ali, So-Woon Kim","doi":"10.1186/s13058-024-01784-y","DOIUrl":"10.1186/s13058-024-01784-y","url":null,"abstract":"<p><strong>Background: </strong>Accurate classification of breast cancer molecular subtypes is crucial in determining treatment strategies and predicting clinical outcomes. This classification largely depends on the assessment of human epidermal growth factor receptor 2 (HER2), estrogen receptor (ER), and progesterone receptor (PR) status. However, variability in interpretation among pathologists pose challenges to the accuracy of this classification. This study evaluates the role of artificial intelligence (AI) in enhancing the consistency of these evaluations.</p><p><strong>Methods: </strong>AI-powered HER2 and ER/PR analyzers, consisting of cell and tissue models, were developed using 1,259 HER2, 744 ER, and 466 PR-stained immunohistochemistry (IHC) whole-slide images of breast cancer. External validation cohort comprising HER2, ER, and PR IHCs of 201 breast cancer cases were analyzed with these AI-powered analyzers. Three board-certified pathologists independently assessed these cases without AI annotation. Then, cases with differing interpretations between pathologists and the AI analyzer were revisited with AI assistance, focusing on evaluating the influence of AI assistance on the concordance among pathologists during the revised evaluation compared to the initial assessment.</p><p><strong>Results: </strong>Reevaluation was required in 61 (30.3%), 42 (20.9%), and 80 (39.8%) of HER2, in 15 (7.5%), 17 (8.5%), and 11 (5.5%) of ER, and in 26 (12.9%), 24 (11.9%), and 28 (13.9%) of PR evaluations by the pathologists, respectively. Compared to initial interpretations, the assistance of AI led to a notable increase in the agreement among three pathologists on the status of HER2 (from 49.3 to 74.1%, p < 0.001), ER (from 93.0 to 96.5%, p = 0.096), and PR (from 84.6 to 91.5%, p = 0.006). This improvement was especially evident in cases of HER2 2+ and 1+, where the concordance significantly increased from 46.2 to 68.4% and from 26.5 to 70.7%, respectively. Consequently, a refinement in the classification of breast cancer molecular subtypes (from 58.2 to 78.6%, p < 0.001) was achieved with AI assistance.</p><p><strong>Conclusions: </strong>This study underscores the significant role of AI analyzers in improving pathologists' concordance in the classification of breast cancer molecular subtypes.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":null,"pages":null},"PeriodicalIF":7.4,"publicationDate":"2024-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10885430/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139941093","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":"Metabolic adaptation towards glycolysis supports resistance to neoadjuvant chemotherapy in early triple negative breast cancers.","authors":"Françoise Derouane, Manon Desgres, Camilla Moroni, Jérôme Ambroise, Martine Berlière, Mieke R Van Bockstal, Christine Galant, Cédric van Marcke, Marianela Vara-Messler, Stefan J Hutten, Jos Jonkers, Larissa Mourao, Colinda L G J Scheele, Francois P Duhoux, Cyril Corbet","doi":"10.1186/s13058-024-01788-8","DOIUrl":"10.1186/s13058-024-01788-8","url":null,"abstract":"<p><strong>Background: </strong>Neoadjuvant chemotherapy (NAC) is the standard of care for patients with early-stage triple negative breast cancers (TNBC). However, more than half of TNBC patients do not achieve a pathological complete response (pCR) after NAC, and residual cancer burden (RCB) is associated with dismal long-term prognosis. Understanding the mechanisms underlying differential treatment outcomes is therefore critical to limit RCB and improve NAC efficiency.</p><p><strong>Methods: </strong>Human TNBC cell lines and patient-derived organoids were used in combination with real-time metabolic assays to evaluate the effect of NAC (paclitaxel and epirubicin) on tumor cell metabolism, in particular glycolysis. Diagnostic biopsies (pre-NAC) from patients with early TNBC were analyzed by bulk RNA-sequencing to evaluate the predictive value of a glycolysis-related gene signature.</p><p><strong>Results: </strong>Paclitaxel induced a consistent metabolic switch to glycolysis, correlated with a reduced mitochondrial oxidative metabolism, in TNBC cells. In pre-NAC diagnostic biopsies from TNBC patients, glycolysis was found to be upregulated in non-responders. Furthermore, glycolysis inhibition greatly improved response to NAC in TNBC organoid models.</p><p><strong>Conclusions: </strong>Our study pinpoints a metabolic adaptation to glycolysis as a mechanism driving resistance to NAC in TNBC. Our data pave the way for the use of glycolysis-related genes as predictive biomarkers for NAC response, as well as the development of inhibitors to overcome this glycolysis-driven resistance to NAC in human TNBC patients.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":null,"pages":null},"PeriodicalIF":7.4,"publicationDate":"2024-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10875828/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139906733","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":"Identification of CD160-TM as a tumor target on triple negative breast cancers: possible therapeutic applications.","authors":"Claire Scheffges, Jérôme Devy, Jérôme Giustiniani, Stessy Francois, Lucille Cartier, Yacine Merrouche, Arnaud Foussat, Stéphane Potteaux, Armand Bensussan, Anne Marie-Cardine","doi":"10.1186/s13058-024-01785-x","DOIUrl":"10.1186/s13058-024-01785-x","url":null,"abstract":"<p><strong>Background: </strong>Despite major therapeutic advances, triple-negative breast cancer (TNBC) still presents a worth prognosis than hormone receptors-positive breast cancers. One major issue relies in the molecular and mutational heterogeneity of TNBC subtypes that is reinforced by the absence of reliable tumor-antigen that could serve as a specific target to further promote efficient tumor cell recognition and depletion. CD160 is a receptor mainly expressed by NK lymphocytes and presenting two isoforms, namely the GPI-anchored form (CD160-GPI) and the transmembrane isoform (CD160-TM). While CD160-GPI is constitutively expressed on resting cells and involved in the generation of NK cells' cytotoxic activity, CD160-TM is neo-synthesized upon activation and promotes the amplification of NK cells' killing ability.</p><p><strong>Methods: </strong>CD160 expression was assessed by immunohistochemistry (IHC) and flow cytometry on TNBC patient biopsies or cell lines, respectively. Antibody (Ab)-mediated tumor depletion was tested in vitro by performing antibody-dependent cell cytotoxicity (ADCC) and phagocytosis (ADCP) assays, and in vivo on a TNBC mouse model.</p><p><strong>Results: </strong>Preliminary data obtained by IHC on TNBC patients' tumor biopsies revealed an unconventional expression of CD160 by TNBC tumor cells. By using a specific but conformation-dependent anti-CD160-TM Ab, we established that CD160-TM, but not CD160-GPI, was expressed by TNBC tumor cells. A conformation-independent anti-CD160-TM mAb (22B12; muIgG2a isotype) was generated and selected according to pre-defined specificity and functional criterions. In vitro functional assays demonstrated that ADCC and ADCP could be induced in the presence of 22B12, resulting in TNBC cell line apoptosis. The ability of 22B12 to exert an in vivo anti-tumor activity was also demonstrated on a TNBC murine model.</p><p><strong>Conclusions: </strong>Our data identify CD160-TM as a tumor marker for TNBC and provide a rational for the use of anti-CD160-TM antibodies as therapeutic tools in this tumor context.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":null,"pages":null},"PeriodicalIF":7.4,"publicationDate":"2024-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10870674/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139742406","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":"MRI-based tumor shrinkage patterns after early neoadjuvant therapy in breast cancer: correlation with molecular subtypes and pathological response after therapy.","authors":"Mengfan Wang, Siyao Du, Si Gao, Ruimeng Zhao, Shasha Liu, Wenhong Jiang, Can Peng, Ruimei Chai, Lina Zhang","doi":"10.1186/s13058-024-01781-1","DOIUrl":"10.1186/s13058-024-01781-1","url":null,"abstract":"<p><strong>Background: </strong>MRI-based tumor shrinkage patterns (TSP) after neoadjuvant therapy (NAT) have been associated with pathological response. However, the understanding of TSP after early NAT remains limited. We aimed to analyze the relationship between TSP after early NAT and pathological response after therapy in different molecular subtypes.</p><p><strong>Methods: </strong>We prospectively enrolled participants with invasive ductal breast cancers who received NAT and performed pretreatment DCE-MRI from September 2020 to August 2022. Early-stage MRIs were performed after the first (1st-MRI) and/or second (2nd-MRI) cycle of NAT. Tumor shrinkage patterns were categorized into four groups: concentric shrinkage, diffuse decrease (DD), decrease of intensity only (DIO), and stable disease (SD). Logistic regression analysis was performed to identify independent variables associated with pathologic complete response (pCR), and stratified analysis according to tumor hormone receptor (HR)/human epidermal growth factor receptor 2 (HER2) disease subtype.</p><p><strong>Results: </strong>344 participants (mean age: 50 years, 113/345 [33%] pCR) with 345 tumors (1 bilateral) had evaluable 1st-MRI or 2nd-MRI to comprise the primary analysis cohort, of which 244 participants with 245 tumors had evaluable 1st-MRI (82/245 [33%] pCR) and 206 participants with 207 tumors had evaluable 2nd-MRI (69/207 [33%] pCR) to comprise the 1st- and 2nd-timepoint subgroup analysis cohorts, respectively. In the primary analysis, multivariate analysis showed that early DD pattern (OR = 12.08; 95% CI 3.34-43.75; p < 0.001) predicted pCR independently of the change in tumor size (OR = 1.37; 95% CI 0.94-2.01; p = 0.106) in HR⁺/HER2^- subtype, and the change in tumor size was a strong pCR predictor in HER2⁺ (OR = 1.61; 95% CI 1.22-2.13; p = 0.001) and triple-negative breast cancer (TNBC, OR = 1.61; 95% CI 1.22-2.11; p = 0.001). Compared with the change in tumor size, the SD pattern achieved a higher negative predictive value in HER2⁺ and TNBC. The statistical significance of complete 1st-timepoint subgroup analysis was consistent with the primary analysis.</p><p><strong>Conclusion: </strong>The diffuse decrease pattern in HR⁺/HER2^- subtype and stable disease in HER2⁺ and TNBC after early NAT could serve as additional straightforward and comprehensible indicators of treatment response.</p><p><strong>Trial registration: </strong>Trial registration at https://www.chictr.org.cn/ .</p><p><strong>Registration number: </strong>ChiCTR2000038578, registered September 24, 2020.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":null,"pages":null},"PeriodicalIF":7.4,"publicationDate":"2024-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10863121/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139724619","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}