Breast Cancer Research最新文献

{"title":"Clustering of HR + /HER2− breast cancer in an Asian cohort is driven by immune phenotypes","authors":"Jia-Wern Pan, Mohana Ragu, Wei-Qin Chan, Siti Norhidayu Hasan, Tania Islam, Li-Ying Teoh, Suniza Jamaris, Mee-Hoong See, Cheng-Har Yip, Pathmanathan Rajadurai, Lai-Meng Looi, Nur Aishah Mohd Taib, Oscar M. Rueda, Carlos Caldas, Suet-Feung Chin, Joanna Lim, Soo-Hwang Teo","doi":"10.1186/s13058-024-01826-5","DOIUrl":"https://doi.org/10.1186/s13058-024-01826-5","url":null,"abstract":"Breast cancer exhibits significant heterogeneity, manifesting in various subtypes that are critical in guiding treatment decisions. This study aimed to investigate the existence of distinct subtypes of breast cancer within the Asian population, by analysing the transcriptomic profiles of 934 breast cancer patients from a Malaysian cohort. Our findings reveal that the HR + /HER2− breast cancer samples display a distinct clustering pattern based on immune phenotypes, rather than conforming to the conventional luminal A-luminal B paradigm previously reported in breast cancers from women of European descent. This suggests that the activation of the immune system may play a more important role in Asian HR + /HER2− breast cancer than has been previously recognized. Analysis of somatic mutations by whole exome sequencing showed that counter-intuitively, the cluster of HR + /HER2− samples exhibiting higher immune scores was associated with lower tumour mutational burden, lower homologous recombination deficiency scores, and fewer copy number aberrations, implicating the involvement of non-canonical tumour immune pathways. Further investigations are warranted to determine the underlying mechanisms of these pathways, with the potential to develop innovative immunotherapeutic approaches tailored to this specific patient population.","PeriodicalId":9222,"journal":{"name":"Breast Cancer Research","volume":"100 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2024-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140635811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Screening mammography performance according to breast density: a comparison between radiologists versus standalone intelligence detection","authors":"Mi-ri Kwon, Yoosoo Chang, Soo-Youn Ham, Yoosun Cho, Eun Young Kim, Jeonggyu Kang, Eun Kyung Park, Ki Hwan Kim, Minjeong Kim, Tae Soo Kim, Hyeonsoo Lee, Ria Kwon, Ga-Young Lim, Hye Rin Choi, JunHyeok Choi, Shin Ho Kook, Seungho Ryu","doi":"10.1186/s13058-024-01821-w","DOIUrl":"https://doi.org/10.1186/s13058-024-01821-w","url":null,"abstract":"Artificial intelligence (AI) algorithms for the independent assessment of screening mammograms have not been well established in a large screening cohort of Asian women. We compared the performance of screening digital mammography considering breast density, between radiologists and AI standalone detection among Korean women. We retrospectively included 89,855 Korean women who underwent their initial screening digital mammography from 2009 to 2020. Breast cancer within 12 months of the screening mammography was the reference standard, according to the National Cancer Registry. Lunit software was used to determine the probability of malignancy scores, with a cutoff of 10% for breast cancer detection. The AI’s performance was compared with that of the final Breast Imaging Reporting and Data System category, as recorded by breast radiologists. Breast density was classified into four categories (A–D) based on the radiologist and AI-based assessments. The performance metrics (cancer detection rate [CDR], sensitivity, specificity, positive predictive value [PPV], recall rate, and area under the receiver operating characteristic curve [AUC]) were compared across breast density categories. Mean participant age was 43.5 ± 8.7 years; 143 breast cancer cases were identified within 12 months. The CDRs (1.1/1000 examination) and sensitivity values showed no significant differences between radiologist and AI-based results (69.9% [95% confidence interval [CI], 61.7–77.3] vs. 67.1% [95% CI, 58.8–74.8]). However, the AI algorithm showed better specificity (93.0% [95% CI, 92.9–93.2] vs. 77.6% [95% CI, 61.7–77.9]), PPV (1.5% [95% CI, 1.2–1.9] vs. 0.5% [95% CI, 0.4–0.6]), recall rate (7.1% [95% CI, 6.9–7.2] vs. 22.5% [95% CI, 22.2–22.7]), and AUC values (0.8 [95% CI, 0.76–0.84] vs. 0.74 [95% CI, 0.7–0.78]) (all P < 0.05). Radiologist and AI-based results showed the best performance in the non-dense category; the CDR and sensitivity were higher for radiologists in the heterogeneously dense category (P = 0.059). However, the specificity, PPV, and recall rate consistently favored AI-based results across all categories, including the extremely dense category. AI-based software showed slightly lower sensitivity, although the difference was not statistically significant. However, it outperformed radiologists in recall rate, specificity, PPV, and AUC, with disparities most prominent in extremely dense breast tissue.","PeriodicalId":9222,"journal":{"name":"Breast Cancer Research","volume":"114 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2024-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140635151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Meeting Abstracts from the British Society of Breast Radiology annual scientific meeting 2023","authors":"","doi":"10.1186/s13058-024-01786-w","DOIUrl":"https://doi.org/10.1186/s13058-024-01786-w","url":null,"abstract":"&lt;p&gt;&lt;b&gt;Proffered Papers&lt;/b&gt;&lt;/p&gt;&lt;p&gt;&lt;b&gt;Monday 6 November 2023&lt;/b&gt;&lt;/p&gt;&lt;p&gt;&lt;b&gt;1:10 PM–2:00 PM&lt;/b&gt;&lt;/p&gt;&lt;p&gt;&lt;i&gt;Abstracts listed in presenting order&lt;/i&gt;&lt;/p&gt;&lt;h3&gt;Dr Jean Seely&lt;sup&gt;1&lt;/sup&gt;, Prof Mohamed Abdolell&lt;sup&gt;2,3&lt;/sup&gt;, Dr Jennifer Payne&lt;sup&gt;2,3&lt;/sup&gt;, Dr Sian Iles&lt;sup&gt;2,3&lt;/sup&gt;, Dr Georgia Spear&lt;sup&gt;4&lt;/sup&gt;, &lt;b&gt;&lt;u&gt;Dr Nisha Sharma&lt;/u&gt;&lt;/b&gt;\u0000&lt;sup&gt;5&lt;/sup&gt;, Dr Laurie R. Margolies&lt;sup&gt;6&lt;/sup&gt;, Dr Sylvia Heywang-Köbrunner&lt;sup&gt;7&lt;/sup&gt;, Dr Toni Vomweg&lt;sup&gt;8&lt;/sup&gt;\u0000&lt;/h3&gt;&lt;h4&gt;\u0000&lt;sup&gt;1&lt;/sup&gt;The Ottawa Hospital, Ottawa, Canada; &lt;sup&gt;2&lt;/sup&gt;Nova Scotia Health Authority, Canada; &lt;sup&gt;3&lt;/sup&gt;Dalhousie University, Halifax, Canada; &lt;sup&gt;4&lt;/sup&gt;NorthShore HealthSystem, Evanston, United States; &lt;sup&gt;5&lt;/sup&gt;Leeds Teaching Hospital, NHS Trust, Leeds, United Kingdom; &lt;sup&gt;6&lt;/sup&gt;Mount Sinai Health System, New York, United States; &lt;sup&gt;7&lt;/sup&gt;Referenzzentrum Mammographie Munchen, Munich, Germany; &lt;sup&gt;8&lt;/sup&gt;Radiologisches Institut Dr von Essen Koblenz, Koblenz, Germany&lt;/h4&gt;&lt;p&gt;&lt;i&gt;Breast Cancer Research&lt;/i&gt; 2024, &lt;b&gt;26(1)&lt;/b&gt;:O1&lt;/p&gt;&lt;p&gt;The COVID-19 pandemic led to recommendations for decreased or ceased breast screening services. Prior studies that examine the COVID-19 impact on mammography volumes are limited to single regions and rates of less than 9 months post-pandemic. This study aims to assess the recovery of screening mammography volumes from 3 months pre COVID-onset through 12 months post COVID-onset across 7 participating sites from four countries.&lt;/p&gt;&lt;p&gt;We collected mammography volume data from 7 breast screening services (Canada, Germany, USA, UK) between December 2019 and April 2021 using an artificial intelligence software tool. The study was approved by the research ethics at participating sites.&lt;/p&gt;&lt;p&gt;249,817 screening mammograms were collected. Of the 7 participating sites, 4 returned to and occasionally exceeded pre-COVID volumes, whereas the other 3 sites approached but did not fully return to pre-COVID volumes in the 12 months post COVID. Sites varied substantially in the time taken to re-initiate screening mammography after the first COVID wave (1–6 months). One site shut down screening services in successive COVID waves, while other sites experienced short dips in volumes but generally recovered within one month.&lt;/p&gt;&lt;p&gt;In the 1-year period post COVID-onset, mammography screening volumes recovered to varying extents at differing rates, with some sites returning to pre-pandemic levels and others lagging behind. This international multi-center study may inform future opportunities for collaboration between sites to develop strategies for increasing screening volumes and sharing best practices for pandemic recovery.&lt;/p&gt;&lt;h3&gt;\u0000&lt;b&gt;&lt;u&gt;Dr Matthew Common&lt;/u&gt;&lt;/b&gt;\u0000&lt;sup&gt;1,2&lt;/sup&gt;, Dr Pat Rohan&lt;sup&gt;1,2&lt;/sup&gt;, Dr Cathal McCarthy&lt;sup&gt;1,2&lt;/sup&gt;, Eithne Downey&lt;sup&gt;1&lt;/sup&gt;, Dr Niamh Hambly&lt;sup&gt;1&lt;/sup&gt;, Dr Neasa ní Mhuircheartaigh&lt;sup&gt;1&lt;/sup&gt;, Dr Jennifer Kerr&lt;sup&gt;1&lt;/sup&gt;, Prof. Colm Power&lt;sup&gt;1,2&lt;/sup&gt;, Prof. Arnold Hill&lt;sup&gt;1,2&lt;/sup&gt;, Dr Deirdre Duke&lt;sup&gt;1,2&lt;/sup&gt;\u0000&lt;/h3&gt;&lt;h4&gt;\u0000&lt;sup&gt;","PeriodicalId":9222,"journal":{"name":"Breast Cancer Research","volume":"188 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140611188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Outcomes of sentinel node biopsy according to MRI response in an association with the subtypes in cN1–3 breast cancer after neoadjuvant systemic therapy, multicenter cohort study","authors":"Soong June Bae, Jung Whan Chun, Sae Byul Lee, Jai Min Ryu, Seok Jin Nam, Joon Jeong, Hyung Seok Park, Sung Gwe Ahn","doi":"10.1186/s13058-024-01807-8","DOIUrl":"https://doi.org/10.1186/s13058-024-01807-8","url":null,"abstract":"This study investigated the feasibility of sentinel lymph node biopsy (SLNB) after neoadjuvant systemic therapy (NAST) in patients with initially high nodal burden. In the multicenter retrospective cohort, 388 individuals with cN1–3 breast cancer who underwent NAST and had SLNB followed by completion axillary lymph node dissection were included. In an external validation cohort, 267 patients with HER2+ or triple-negative breast cancer (TNBC) meeting similar inclusion criteria were included. Primary outcome was the false-negative rates (FNRs) of SLNB according to the MRI response and subtypes. We defined complete MRI responders as patients who experienced disappearance of suspicious features in the breast and axilla after NAST. In the multicenter retrospective cohort, 130 (33.5%) of 388 patients were of cN2-3, and 55 (14.2%) of 388 patients showed complete MRI responses. In hormone receptor-positive HER2− (n = 207), complete and non-complete responders had a high FNRs (31.3% [95% CI 8.6–54.0] and 20.9% [95% CI 14.1–27.6], respectively). However, in HER2+ or TNBC (n = 181), the FNR of complete MRI responders was 0% (95% CI 0–0), whereas that of non-complete responders was 33.3% (95% CI 20.8–45.9). When we validated our findings in the external cohort with HER2+ or TNBC (n = 267), of which 34.2% were cN2-3, the FNRs of complete were 7.1% (95% CI 0–16.7). Our findings suggest that SLNB can be a reliable option for nodal status evaluation in selected patients who have responded well to NAST, especially in HER2+ and TNBC patients who show a complete MRI response.","PeriodicalId":9222,"journal":{"name":"Breast Cancer Research","volume":"100 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140611421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Selective omission of sentinel lymph node biopsy in mastectomy for ductal carcinoma in situ: identifying eligible candidates","authors":"Soong June Bae, Yoonwon Kook, Ji Soo Jang, Seung Ho Baek, Sohyun Moon, Jung Hyun Kim, Seung Eun Lee, Min Ji Kim, Sung Gwe Ahn, Joon Jeong","doi":"10.1186/s13058-024-01816-7","DOIUrl":"https://doi.org/10.1186/s13058-024-01816-7","url":null,"abstract":"Sentinel lymph node biopsy (SLNB) is recommended for patients with ductal carcinoma in situ (DCIS) undergoing mastectomy, given the concerns regarding upstaging and technical difficulties of post-mastectomy SLNB. However, this may lead to potential overtreatment, considering favorable prognosis and de-escalation trends in DCIS. Data regarding upstaging and axillary lymph node metastasis among these patients remain limited. We retrospectively reviewed patients with DCIS who underwent mastectomy with SLNB or axillary lymph node dissection at Gangnam Severance Hospital between January 2010 and December 2021. To explore the feasibility of omitting SLNB, we assessed the rates of DCIS upgraded to invasive carcinoma and axillary lymph node metastasis. Binary Cox regression analysis was performed to identify clinicopathologic factors associated with upstaging and axillary lymph node metastasis. Among 385 patients, 164 (42.6%) experienced an invasive carcinoma upgrade: microinvasion, pT1, and pT2 were confirmed in 53 (13.8%), 97 (25.2%), and 14 (3.6%) patients, respectively. Seventeen (4.4%) patients had axillary lymph node metastasis. Multivariable analysis identified age ≤ 50 years (adjusted odds ratio [OR], 12.73; 95% confidence interval [CI], 1.18–137.51; p = 0.036) and suspicious axillary lymph nodes on radiologic evaluation (adjusted OR, 9.31; 95% CI, 2.06–41.99; p = 0.004) as independent factors associated with axillary lymph node metastasis. Among patients aged > 50 years and/or no suspicious axillary lymph nodes, only 1.7–2.3%) experienced axillary lymph node metastasis. Although underestimation of the invasive component was relatively high among patients with DCIS undergoing mastectomy, axillary lymph node metastasis was rare. Our findings suggest that omitting SLNB may be feasible for patients over 50 and/or without suspicious axillary lymph nodes on radiologic evaluation.","PeriodicalId":9222,"journal":{"name":"Breast Cancer Research","volume":"11 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2024-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140578735","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolomics assisted by transcriptomics analysis to reveal metabolic characteristics and potential biomarkers associated with treatment response of neoadjuvant therapy with TCbHP regimen in HER2 + breast cancer","authors":"Ningning Zhang, Yuxin Huang, Guanwen Wang, Yimei Xiang, Zhouhong Jing, Junjie Zeng, Feng Yu, Xianjun Pan, Wenqi Zhou, Xiaohua Zeng","doi":"10.1186/s13058-024-01813-w","DOIUrl":"https://doi.org/10.1186/s13058-024-01813-w","url":null,"abstract":"This study aimed to explore potential indicators associated with the neoadjuvant efficacy of TCbHP regimen (taxane, carboplatin, trastuzumab, and pertuzumab) in HER2 + breast cancer (BrCa) patients. A total of 120 plasma samples from 40 patients with HER2 + BrCa were prospectively collected at three treatment times of neoadjuvant therapy (NAT) with TCbHP regimen. Serum metabolites were analyzed based on LC-MS and GC-MS data. Random forest was used to establish predictive models based on pre-therapeutic differentially expressed metabolites. Time series analysis was used to obtain potential monitors for treatment response. Transcriptome analysis was performed in nine available pre‑therapeutic specimens of core needle biopsies. Integrated analyses of metabolomics and transcriptomics were also performed in these nine patients. qRT-PCR was used to detect altered genes in trastuzumab-sensitive and trastuzumab-resistant cell lines. Twenty-one patients achieved pCR, and 19 patients achieved non-pCR. There were significant differences in plasma metabolic profiles before and during treatment. A total of 100 differential metabolites were identified between pCR patients and non-pCR patients at baseline; these metabolites were markedly enriched in 40 metabolic pathways. The area under the curve (AUC) values for discriminating the pCR and non-PCR groups from the NAT of the single potential metabolite [sophorose, N-(2-acetamido) iminodiacetic acid, taurine and 6-hydroxy-2-aminohexanoic acid] or combined panel of these metabolites were greater than 0.910. Eighteen metabolites exhibited potential for monitoring efficacy. Several validated genes might be associated with trastuzumab resistance. Thirty-nine altered pathways were found to be abnormally expressed at both the transcriptional and metabolic levels. Serum-metabolomics could be used as a powerful tool for exploring informative biomarkers for predicting or monitoring treatment efficacy. Metabolomics integrated with transcriptomics analysis could assist in obtaining new insights into biochemical pathophysiology and might facilitate the development of new treatment targets for insensitive patients.","PeriodicalId":9222,"journal":{"name":"Breast Cancer Research","volume":"17 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2024-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140578637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chitin-mediated blockade of chitinase-like proteins reduces tumor immunosuppression, inhibits lymphatic metastasis and enhances anti-PD-1 efficacy in complementary TNBC models","authors":"Robbe Salembier, Caro De Haes, Julie Bellemans, Kristel Demeyere, Wim Van Den Broeck, Niek N. Sanders, Steven Van Laere, Traci R. Lyons, Evelyne Meyer, Jonas Steenbrugge","doi":"10.1186/s13058-024-01815-8","DOIUrl":"https://doi.org/10.1186/s13058-024-01815-8","url":null,"abstract":"Chitinase-like proteins (CLPs) play a key role in immunosuppression under inflammatory conditions such as cancer. CLPs are enzymatically inactive and become neutralized upon binding of their natural ligand chitin, potentially reducing CLP-driven immunosuppression. We investigated the efficacy of chitin treatment in the context of triple-negative breast cancer (TNBC) using complementary mouse models. We also evaluated the immunomodulatory influence of chitin on immune checkpoint blockade (ICB) and compared its efficacy as general CLP blocker with blockade of a single CLP, i.e. chitinase 3-like 1 (CHI3L1). Female BALB/c mice were intraductally injected with luciferase-expressing 4T1 or 66cl4 cells and systemically treated with chitin in combination with or without anti-programmed death (PD)-1 ICB. For single CLP blockade, tumor-bearing mice were treated with anti-CHI3L1 antibodies. Metastatic progression was monitored through bioluminescence imaging. Immune cell changes in primary tumors and lymphoid organs (i.e. axillary lymph nodes and spleen) were investigated through flow cytometry, immunohistochemistry, cytokine profiling and RNA-sequencing. CHI3L1-stimulated RAW264.7 macrophages were subjected to 2D lymphatic endothelial cell adhesion and 3D lymphatic integration in vitro assays for studying macrophage-mediated lymphatic remodeling. Chitin significantly reduced primary tumor progression in the 4T1-based model by decreasing the high production of CLPs that originate from tumor-associated neutrophils (TANs) and Stat3 signaling, prominently affecting the CHI3L1 and CHI3L3 primary tumor levels. It reduced immunosuppressive cell types and increased anti-tumorigenic T-cells in primary tumors as well as axillary lymph nodes. Chitin also significantly reduced CHI3L3 primary tumor levels and immunosuppression in the 66cl4-based model. Compared to anti-CHI3L1, chitin enhanced primary tumor growth reduction and anti-tumorigenicity. Both treatments equally inhibited lymphatic adhesion and integration of macrophages, thereby hampering lymphatic tumor cell spreading. Upon ICB combination therapy, chitin alleviated anti-PD-1 resistance in both TNBC models, providing a significant add-on reduction in primary tumor and lung metastatic growth compared to chitin monotherapy. These add-on effects occurred through additional increase in CD8α+ T-cell infiltration and activation in primary tumor and lymphoid organs. Chitin, as a general CLP blocker, reduces CLP production, enhances anti-tumor immunity as well as ICB responses, supporting its potential clinical relevance in immunosuppressed TNBC patients.","PeriodicalId":9222,"journal":{"name":"Breast Cancer Research","volume":"31 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2024-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140578742","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serum protein profiling reveals an inflammation signature as a predictor of early breast cancer survival","authors":"Peeter Karihtala, Suvi-Katri Leivonen, Ulla Puistola, Elina Urpilainen, Anniina Jääskeläinen, Sirpa Leppä, Arja Jukkola","doi":"10.1186/s13058-024-01812-x","DOIUrl":"https://doi.org/10.1186/s13058-024-01812-x","url":null,"abstract":"Breast cancers exhibit considerable heterogeneity in their biology, immunology, and prognosis. Currently, no validated, serum protein-based tools are available to evaluate the prognosis of patients with early breast cancer. The study population consisted of 521 early-stage breast cancer patients with a median follow-up of 8.9 years. Additionally, 61 patients with breast fibroadenoma or atypical ductal hyperplasia were included as controls. We used a proximity extension assay to measure the preoperative serum levels of 92 proteins associated with inflammatory and immune response processes. The invasive cancers were randomly split into discovery (n = 413) and validation (n = 108) cohorts for the statistical analyses. Using LASSO regression, we identified a nine-protein signature (CCL8, CCL23, CCL28, CSCL10, S100A12, IL10, IL10RB, STAMPB2, and TNFβ) that predicted various survival endpoints more accurately than traditional prognostic factors. In the time-dependent analyses, the prognostic power of the model remained rather stable over time. We also developed and validated a 17-protein model with the potential to differentiate benign breast lesions from malignant lesions (Wilcoxon p < 2.2*10− 16; AUC 0.94). Inflammation and immunity-related serum proteins have the potential to rise above the classical prognostic factors of early-stage breast cancer. They may also help to distinguish benign from malignant breast lesions.","PeriodicalId":9222,"journal":{"name":"Breast Cancer Research","volume":"4 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140578739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"U2AF2-SNORA68 promotes triple-negative breast cancer stemness through the translocation of RPL23 from nucleoplasm to nucleolus and c-Myc expression","authors":"Wenrong Zhang, Xinyue Song, Zining Jin, Yiqi Zhang, Shan Li, Feng Jin, Ang Zheng","doi":"10.1186/s13058-024-01817-6","DOIUrl":"https://doi.org/10.1186/s13058-024-01817-6","url":null,"abstract":"Small nucleolar RNAs (snoRNAs) play key roles in ribosome biosynthesis. However, the mechanism by which snoRNAs regulate cancer stemness remains to be fully elucidated. SNORA68 expression was evaluated in breast cancer tissues by in situ hybridization and qRT‒PCR. Proliferation, migration, apoptosis and stemness analyses were used to determine the role of SNORA68 in carcinogenesis and stemness maintenance. Mechanistically, RNA pull-down, RNA immunoprecipitation (RIP), cell fractionation and coimmunoprecipitation assays were conducted. SNORA68 exhibited high expression in triple-negative breast cancer (TNBC) and was significantly correlated with tumor size (P = 0.048), ki-67 level (P = 0.037), and TNM stage (P = 0.015). The plasma SNORA68 concentration was significantly lower in patients who achieved clinical benefit. The SNORA68-high patients had significantly shorter disease-free survival (DFS) (P = 0.036). Functionally, SNORA68 was found to promote the cell stemness and carcinogenesis of TNBC in vitro and in vivo. Furthermore, elevated SNORA68 expression led to increased nucleolar RPL23 expression and retained RPL23 in the nucleolus by binding U2AF2. RPL23 in the nucleolus subsequently upregulated c-Myc expression. This pathway was validated using a xenograft model. U2AF2-SNORA68 promotes TNBC stemness by retaining RPL23 in the nucleolus and increasing c-Myc expression, which provides new insight into the regulatory mechanism of stemness.","PeriodicalId":9222,"journal":{"name":"Breast Cancer Research","volume":"10 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140578729","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical factors associated with patterns of endocrine therapy adherence in premenopausal breast cancer patients","authors":"Kirsten M. Woolpert, Julie A. Schmidt, Thomas P. Ahern, Cathrine F. Hjorth, Dóra K. Farkas, Bent Ejlertsen, Lindsay J. Collin, Timothy L. Lash, Deirdre P. Cronin-Fenton","doi":"10.1186/s13058-024-01819-4","DOIUrl":"https://doi.org/10.1186/s13058-024-01819-4","url":null,"abstract":"Patients with hormone receptor positive breast cancer are recommended at least five years of adjuvant endocrine therapy, but adherence to this treatment is often suboptimal. We investigated longitudinal trends in adjuvant endocrine therapy (AET) adherence among premenopausal breast cancer patients and identified clinical characteristics, including baseline comorbidities and non-cancer chronic medication use, associated with AET adherence. We included stage I–III premenopausal breast cancer patients diagnosed during 2002–2011 and registered in the Danish Breast Cancer Group clinical database who initiated AET. We used group-based trajectory modeling to describe AET adherence patterns. We also linked patients to Danish population-based registries and fit multinomial logistic models to compute odds ratios (ORs) and 95% confidence intervals (95% CIs) associating clinical characteristics with AET adherence patterns. We identified three adherence patterns among 4,353 women—high adherers (57%), slow decliners (36%), and rapid decliners (6.9%). Women with stage I disease (vs. stage II; OR: 1.9, 95% CI 1.5, 2.5), without chemotherapy (vs. chemotherapy; OR: 4.3, 95% CI 3.0, 6.1), with prevalent comorbid disease (Charlson Comorbidity Index score ≥ 1 vs. 0; OR: 1.6, 95% CI 1.1, 2.3), and with a history of chronic non-cancer medication use (vs. none; OR: 1.3, 95% CI 1.0, 1.8) were more likely to be rapid decliners compared with high adherers. Women with stage I cancer, no chemotherapy, higher comorbidity burden, and history of chronic non-cancer medication use were less likely to adhere to AET. Taking steps to promote adherence in these groups of women may reduce their risk of recurrence.","PeriodicalId":9222,"journal":{"name":"Breast Cancer Research","volume":"101 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2024-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140578727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}