NPJ Breast Cancer最新文献

{"title":"Predictors of response to CDK4/6i retrial after prior CDK4/6i failure in ER+ metastatic breast cancer.","authors":"Nicholas Mai, Carlos H Dos Anjos, Pedram Razavi, Anton Safonov, Sujata Patil, Yuan Chen, Joshua Z Drago, Shanu Modi, Jacqueline F Bromberg, Chau T Dang, Dazhi Liu, Larry Norton, Mark Robson, Sarat Chandarlapaty, Komal Jhaveri","doi":"10.1038/s41523-024-00699-3","DOIUrl":"10.1038/s41523-024-00699-3","url":null,"abstract":"<p><p>After disease progression on endocrine therapy (ET) plus a CDK4/6 inhibitor, there is no standardized sequence for subsequent treatment lines for estrogen receptor positive (ER+) metastatic breast cancer (MBC). CDK4/6i retrial as a treatment strategy is commonplace in modern clinical practice; however, the available prospective data investigating this strategy have had inconclusive results. To frame this data in a real-world context, we performed a retrospective analysis assessing the efficacy of CDK4/6is in 195 patients who had previous exposure to CDK4/6i in a prior treatment line at our institution. Among patients who had stopped a CDK4/6i due to toxicity, CDK4/6i retrial either immediately after with a different CDK4/6i or in a further treatment line with the same initial CDK4/6i was both safe and effective, with a median time to treatment failure (TTF) of 10.1 months (95%CI, 4.8-16.9). For patients whose disease progressed on a prior CDK4/6i, we demonstrated comparable median TTFs for patients rechallenged with the same CDK4/6i (4.3 months, 95%CI 3.2-5.5) and with a different CDK4/6i (4.7 months, 95%CI 3.7-6.0) when compared to the recent PACE, PALMIRA, and MAINTAIN trials. Exploratory genomic analysis suggested that the presence of mutations known to confer CDK4/6i resistance, such as TP53 mutations, CDK4 amplifications, and RB1 or FAT1 loss of function mutations may be molecular biomarkers predictive of CDK4/6i retrial failure.</p>","PeriodicalId":19247,"journal":{"name":"NPJ Breast Cancer","volume":"10 1","pages":"92"},"PeriodicalIF":6.5,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11489574/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142471032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasma C-peptide mammographic features and risk of breast cancer.","authors":"Shadi Azam, Cheng Peng, Bernard A Rosner, Marcus D Goncalves, Erica Phillips, Heather Eliassen, John Heine, Susan E Hankinson, Rulla M Tamimi","doi":"10.1038/s41523-024-00702-x","DOIUrl":"https://doi.org/10.1038/s41523-024-00702-x","url":null,"abstract":"<p><p>Our study in the Nurses' Health Study (NHS) and NHS2, a nested case-control study with 1260 cases and 2221 controls, investigated the association between C-peptide levels, mammographic density (MD) parameters, V (a measure of gray scale variation), and breast cancer (BC) risk. We also examined how C-peptide and BC risk vary across quartiles of mammographic features. Linear and logistic regressions were used to study the associations between C-peptide and MD parameters, and breast cancer. C-peptide was inversely associated with percent MD and positively with non-dense area, but no associations were found with dense area and V measure. C-peptide was associated with an increased risk of invasive BC risk (top vs. bottom quartile, odds ratio = 1.46, 95% CI: 1.12-1.91). No multiplicative interactions were found between C-peptide, MD parameters, and BC risk. Our results suggest a positive association between C-peptide and BC risk, and MD parameters do not seem to modify this association.</p>","PeriodicalId":19247,"journal":{"name":"NPJ Breast Cancer","volume":"10 1","pages":"91"},"PeriodicalIF":6.5,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11487244/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142485703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Validation study of risk-reduction activities after personalized breast cancer education tool in the WISDOM study.","authors":"Tianyi Wang, Mandy Che, Yash S Huilgol, Holly Keane, Deborah Goodman, Rashna Soonavala, Elissa Ozanne, Yiwey Shieh, Jeffrey K Belkora, Allison Stover Fiscalini, Laura J Esserman","doi":"10.1038/s41523-024-00681-z","DOIUrl":"https://doi.org/10.1038/s41523-024-00681-z","url":null,"abstract":"<p><p>Breast cancer risk reduction strategies have been well-validated, but barriers remain for high-risk individuals to adopt them. We performed a study among participants with high risk of breast cancer to validate whether a virtual breast health decision tool impacted a participant's willingness to start risk-reducing activities, identify barriers to adopting these strategies, and understand if it affects breast cancer anxiety. The study sample was 318 participants in the personalized (investigational) arm of the Women Informed to Screen Depending on Measures of risk (WISDOM) clinical trial. After reviewing the tool, these participants completed a feedback survey. We demonstrated that 15 (4.7%) women were taking endocrine risk reduction, 123 (38.7%) were reducing alcohol intake, and 199 (62.6%) were exercising. In the three-month follow-up survey of 109 respondents, only 8 of 61 (13.1%) women who considered endocrine risk reduction pursued it. In contrast, 11 of 16 (68%) participants who considered alcohol reduction pursued the activity, and 14 of 24 (58%) women who considered exercise followed through. Participants listed fear of side effects as the most common barrier to endocrine risk reduction. We also present further steps to be taken to improve the effectiveness of the Breast Health Decisions tool.</p>","PeriodicalId":19247,"journal":{"name":"NPJ Breast Cancer","volume":"10 1","pages":"90"},"PeriodicalIF":6.5,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11471852/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142471041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discerning the impact of ctDNA detection on patient decision-making in early-stage breast cancer.","authors":"Tarah J Ballinger, Mary Lou Smith, Elda Railey, Greg Zimet, Bryan P Schneider","doi":"10.1038/s41523-024-00701-y","DOIUrl":"10.1038/s41523-024-00701-y","url":null,"abstract":"<p><p>The impact of knowledge of circulating tumor DNA (ctDNA) status on patient decisions in high-risk triple-negative breast cancer (TNBC) weighing benefit and toxicity is unknown. Here, 286 women with a history of non-metastatic breast cancer who had received chemotherapy completed a survey mimicking scenarios of residual TNBC after chemotherapy and unknown, negative, or positive ctDNA status to determine the shift in the decision to receive adjuvant therapy. Participants were then presented scenarios mimicking possible post-neoadjuvant therapies and rated acceptability. A general linear model with repeated measures determined contributions of risk reduction and toxicity. When the hypothetical risk of recurrence mimicked ctDNA negativity, significantly less participants were accepting of adjuvant capecitabine versus no therapy. When presented with ctDNA positivity and increased recurrence risk, the degree of benefit impacted acceptability more than the toxicity profile. As genomic technology advances and ctDNA assays become commercially available, it is imperative to understand the impact on patient decision-making.</p>","PeriodicalId":19247,"journal":{"name":"NPJ Breast Cancer","volume":"10 1","pages":"89"},"PeriodicalIF":6.5,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11461894/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142392117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical and immune responses to neoadjuvant fulvestrant with or without enzalutamide in ER+/Her2- breast cancer.","authors":"Anthony D Elias, Alyse W Staley, Monica Fornier, Gregory A Vidal, Vida Alami, Sharon Sams, Nicole S Spoelstra, Andrew Goodspeed, Peter Kabos, Jennifer R Diamond, Elena Shagisultanova, Rosa I Gallagher, Julia D Wulfkuhle, Emanuel F Petricoin, Kathryn L Zolman, Tessa McSpadden, Kimberly R Jordan, Jill E Slansky, Virginia F Borges, Dexiang Gao, Jennifer K Richer","doi":"10.1038/s41523-024-00697-5","DOIUrl":"10.1038/s41523-024-00697-5","url":null,"abstract":"<p><p>Most ER+ breast cancers (BC) express androgen receptors (AR). This randomized phase II trial of 4 months of neoadjuvant fulvestrant (Fulv) alone or with enzalutamide (Combo) assessed whether adding AR blockade to Fulv would limit residual tumor at the time of surgery, as measured by modified preoperative endocrine predictive index (PEPI) score. Eligible patients were women with ER+/HER2- primary BC cT2 or greater. Stratification factors were clinical node and T-stage. Fresh tumor biopsies were required at study entry, after 4 weeks on therapy (W5), and at surgery. Laboratory analyses on tumors included immunochemistry (IHC) for ER/PR/AR/GR and Ki67 protein, evaluation of gene expression, multiplex for myeloid lineage immune cells, reverse-phase protein array, and plasma metabolomic analyses. Of 69 consented patients, 59 were evaluable. Toxicity was as expected with endocrine therapy. Combo achieved PEPI = 0 more frequently (24%: 8/33) than Fulv (8%: 2/26). Ki67 was ≤10% across arms by W5 in 76% of tumors. Activation of mTOR pathway proteins was elevated in tumors with poor Ki67 response. Tumors in both arms showed decreased estrogen-regulated and cell division gene sets, while Combo arm tumors uniquely exhibited enrichment of immune activation gene sets, including interferon gamma, complement, inflammation, antigen processing, and B and T cell activation. Multiplex IHC showed significantly reduced tumor-associated macrophages and CD14+/HLADR-/CD68- MDSCs in Combo tumors at W5. In summary, Combo tumors showed a higher PEPI = 0 response, Ki67 response, and more activated tumor immune microenvironment than Fulv. The odds of response were 4.6-fold higher for patients with ILC versus IDC. (Trial registration: This trial is registered at Clinicaltrials.gov ( https://www.clinicaltrials.gov/study/NCT02955394?id=16-1042&rank=1 ). The trial registration number is NCT02955394. The full trial protocol is available under Study Details at the Clinicaltrials.gov link provided).</p>","PeriodicalId":19247,"journal":{"name":"NPJ Breast Cancer","volume":"10 1","pages":"88"},"PeriodicalIF":6.5,"publicationDate":"2024-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11455938/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142378133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cancer risk assessment of premalignant breast tissues from patients with BRCA mutations by genome profiling.","authors":"Takeshi Hirose, Masachika Ikegami, Kumiko Kida, Toshihide Ueno, Rina Kitada, Lei Wang, Shinya Tanaka, Makoto Endo, Yasuharu Nakashima, Naoki Kanomata, Hiroyuki Mano, Hideko Yamauchi, Shinji Kohsaka","doi":"10.1038/s41523-024-00693-9","DOIUrl":"10.1038/s41523-024-00693-9","url":null,"abstract":"<p><p>Patients with germline pathogenic variants of BRCA1/2 genes have a particular predisposition to develop breast cancer. No clinical test has been developed to accurately and quantitatively evaluate their risk of developing breast cancer. We hypothesized that aberrant cell clonal expansion may be initiated in normal breast tissues without manifesting pathologic changes. To assess the prevalence of clonal expansion in the normal breast, we collected normal breast tissue from 24 breast cancer patients who had undergone surgical resection and 5 carriers of pathogenic BRCA1/2 variant who had undergone prophylactic mastectomy. Whole-exome sequencing (WES) was conducted in 97 specimens from 14 individuals, and TOP panel, a gene panel targeting 464 genes, was conducted in 321 specimens from 26 individuals, including 8 individuals with germline pathogenic variants of BRCA1/2 genes. Recurrent oncogenic mutations within PIK3CA, ARHGAP35, HRAS, and NF1 were identified in normal breast tissue at considerable variant allelic frequencies (VAF), suggesting clonal expansion. In addition, 937 normal breast tissues were evaluated using the Breast Cancer Panel (BCP) targeting 25 genes to determine the exact prevalence and distribution of clonal expansion. To assess the clonal expansion, we developed the clonality score, which is the mean value of clonal cell fractions for samples obtained from a given breast. The average clonality score in macroscopically normal breast tissue was 0.95 (0-2.46), with a significant difference between cases with and without a history of breast cancer of stage 2 or more advanced stage (p = 0.01). Additional WES on 42 samples with relatively large clone size (VAF > 3%) confirmed that these cell clones harbored multiple mutations (10.7 mutations/sample), and the number of existing mutations was consistent with the clone size (R = 0.50). The results suggest that clonal changes occur in normal breast tissue of women at high risk for breast cancer even before cancer is detected pathologically and/or radiologically, and the clonality score shows the potential to be a valid method of evaluating clonal expansion for cancer-risk assessment that provides appropriate preventive options for patients at high risk for breast cancer.</p>","PeriodicalId":19247,"journal":{"name":"NPJ Breast Cancer","volume":"10 1","pages":"87"},"PeriodicalIF":6.5,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11452615/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142375734","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic and therapeutic implications of tumor-restrictive type III collagen in the breast cancer microenvironment.","authors":"Daniel C Stewart, Becky K Brisson, Bassil Dekky, Ashton C Berger, William Yen, Elizabeth A Mauldin, Claudia Loebel, Deborah Gillette, Charles-Antoine Assenmacher, Corisa Quincey, Darko Stefanovski, Massimo Cristofanilli, Edna Cukierman, Jason A Burdick, Virginia F Borges, Susan W Volk","doi":"10.1038/s41523-024-00690-y","DOIUrl":"10.1038/s41523-024-00690-y","url":null,"abstract":"<p><p>Collagen plays a critical role in regulating breast cancer progression and therapeutic resistance. An improved understanding of both the features and drivers of tumor-permissive and -restrictive collagen matrices are critical to improve prognostication and develop more effective therapeutic strategies. In this study, using a combination of in vitro, in vivo and bioinformatic experiments, we show that type III collagen (Col3) plays a tumor-restrictive role in human breast cancer. We demonstrate that Col3-deficient, human fibroblasts produce tumor-permissive collagen matrices that drive cell proliferation and suppress apoptosis in non-invasive and invasive breast cancer cell lines. In human triple-negative breast cancer biopsy samples, we demonstrate elevated deposition of Col3 relative to type I collagen (Col1) in non-invasive compared to invasive regions. Similarly, bioinformatics analysis of over 1000 breast cancer patient biopsies from The Cancer Genome Atlas BRCA cohort revealed that patients with higher Col3:Col1 bulk tumor expression had improved overall, disease-free, and progression-free survival relative to those with higher Col1:Col3 expression. Using an established 3D culture model, we show that Col3 increases spheroid formation and induces the formation of lumen-like structures that resemble non-neoplastic mammary acini. Finally, our in vivo study shows co-injection of murine breast cancer cells (4T1) with rhCol3-supplemented hydrogels limits tumor growth and decreases pulmonary metastatic burden compared to controls. Taken together, these data collectively support a tumor-suppressive role for Col3 in human breast cancer and suggest that strategies that increase Col3 may provide a safe and effective therapeutic modality to limit recurrence in breast cancer patients.</p>","PeriodicalId":19247,"journal":{"name":"NPJ Breast Cancer","volume":"10 1","pages":"86"},"PeriodicalIF":6.5,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11447064/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142365930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacokinetics and pharmacogenomics of ribociclib in black patients with metastatic breast cancer the LEANORA study.","authors":"Ilana Schlam, D Max Smith, Cody Peer, Tristan Sissung, Keith T Schmidt, Ming Tan, Ami Chitalia, Nanette H Bishopric, Seth Steinberg, Hyoyoung Choo-Wosoba, Giulia Napoli, Christopher Gallagher, Nadia Ashai, Kristen Whitaker, Candace Mainor, Shruti Tiwari, Nicole Swanson, Stacy Malloy, Claudine Isaacs, William Douglas Figg, Sandra M Swain","doi":"10.1038/s41523-024-00692-w","DOIUrl":"10.1038/s41523-024-00692-w","url":null,"abstract":"<p><p>Underrepresented populations' participation in clinical trials remains limited, and the potential impact of genomic variants on drug metabolism remains elusive. This study aimed to assess the pharmacokinetics (PK) and pharmacogenomics (PGx) of ribociclib in self-identified Black women with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2) advanced breast cancer. LEANORA (NCT04657679) was a prospective, observational, multicenter cohort study involving 14 Black women. PK and PGx were evaluated using tandem mass spectrometry and PharmacoScan™ microarray (including CYP3A5*3, *6, and *7). CYP3A5 phenotypes varied among participants: 7 poor metabolizers (PM), 6 intermediate metabolizers (IM), and one normal metabolizer (NM). The area under the curve did not significantly differ between PMs (39,230 h*ng/mL) and IM/NMs (43,546 h*ng/mL; p = 0.38). The incidence of adverse events (AEs) was also similar. We found no association between CYP3A5 genotype and ribociclib exposure. Continued efforts are needed to include diverse populations in clinical trials to ensure equitable treatment outcomes.</p>","PeriodicalId":19247,"journal":{"name":"NPJ Breast Cancer","volume":"10 1","pages":"84"},"PeriodicalIF":6.5,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11442496/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142350937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Computerized cognitive training improves cognitive function in primary breast cancer survivors.","authors":"Karl R Kleinknecht, Mira Bierend, Lisa-Maria Keim, Frederik Bartels, Amit Lampit, Carsten Finke","doi":"10.1038/s41523-024-00694-8","DOIUrl":"10.1038/s41523-024-00694-8","url":null,"abstract":"<p><p>Cancer-related cognitive impairment has a significant impact on the quality of life and perceived cognitive ability of breast cancer patients and frequently affects attention, working memory, and executive function. Several interventional approaches to treat these deficits have been studied, including web-based cognitive training, but methods and timing in relation to cancer treatment are heterogeneous. Only few interventions start early after primary breast cancer treatment, a time when many patients report the greatest impairments in quality of life and cognition. In this randomized controlled pilot study, 31 breast cancer survivors with subjective cognitive deficits and a mean post-treatment duration of 6.6 months (SD = 9.3) were assigned to either 14 weeks of a web-based cognitive training program (training group, n = 16) or a control group (n = 15). All patients underwent detailed neuropsychological assessment, evaluation of patient-reported outcomes (PROMs), and neurological examination before (baseline, T1) and after (follow-up, T2) the intervention. Longitudinal (T1 vs. T2) and cross-sectional (T2) cognitive performance was assessed for both groups. Overall cognitive impairment significantly improved in the training group following training (56% vs 25%; p = 0.03, Phi = 0.51), but not in the control group (73% vs. 73%; p = 1) in the longitudinal analysis (T1 vs. T2). Specifically, the training group showed statistically significant improvement of executive functions (p = 0.004, Phi = 0.32). No effects of training on subjective cognitive deficits or PROMs were observed. Comparing cross-sectional cognitive performance at follow-up (T2), the training group showed a significantly lower rate of cognitive impairment overall (p = 0.007, Phi = 0.48) and a better cognitive performance for executive function (p = 0.04, Phi = 0.32) compared to the control group. In this prospective pilot study, web-based cognitive training was efficacious in improving overall cognitive performance and executive function. Importantly, this study investigated a web-based cognitive training for the immediate post-treatment phase, when up to 75% of breast cancer patients experience cognitive decline. These results indicate that cognitive training may improve neuropsychological outcomes for patients with breast cancer.</p>","PeriodicalId":19247,"journal":{"name":"NPJ Breast Cancer","volume":"10 1","pages":"85"},"PeriodicalIF":6.5,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11443049/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142350936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SPP1+ macrophages in HR+ breast cancer are associated with tumor-infiltrating lymphocytes.","authors":"Su Min Cha, Jung-Wook Park, Yoon Jae Lee, Hee Jae Lee, Hyeonjin Lee, In Won Lee, Gyungyub Gong, Sung Hee Park, Hee Jin Lee, Byung-Kwan Jeong","doi":"10.1038/s41523-024-00695-7","DOIUrl":"10.1038/s41523-024-00695-7","url":null,"abstract":"<p><p>Breast cancer categorized into hormone receptor-positive (HR+), HER2-positive (HER2+), and triple-negative (TNBC) subtypes, exhibits varied outcomes based on the number of tumor-infiltrating lymphocytes (TILs). To explore the divergent roles of TIL levels across different subtypes, we employed single-cell RNA sequencing on 31 patients with breast cancer. HR+ breast cancer with high TIL levels (TIL-high) revealed increased SPP1+ macrophages, increased SPP1 expression in other monocytes/macrophages (mono/macro) subgroups, and enriched pathways associated with extracellular matrix (ECM) remodeling in mono/macro. Moreover, cell-cell interaction analyses revealed enhanced SPP1, MIF, and FN1 signaling in the interaction between SPP1+ macrophages and T-cells in TIL-high HR+ breast cancer. Spatial transcriptomics data highlighted the close proximity of SPP1+ macrophages, CD8+ T-cells, and CD4+ T-cells in TIL-high HR+ breast cancer. Our findings unveil the novel influence of SPP1+ macrophages on T-cells in TIL-high HR+ breast cancer, potentially explaining the poor prognosis and offering insights for targeted interventions.</p>","PeriodicalId":19247,"journal":{"name":"NPJ Breast Cancer","volume":"10 1","pages":"83"},"PeriodicalIF":6.5,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11442831/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142350938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}