首页 > 最新文献

Breast Cancer Research最新文献

英文 中文
Clustering of HR + /HER2− breast cancer in an Asian cohort is driven by immune phenotypes 亚洲队列中 HR + /HER2- 乳腺癌的聚集是由免疫表型驱动的
IF 7.4 1区 医学 Pub Date : 2024-04-22 DOI: 10.1186/s13058-024-01826-5
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
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.
乳腺癌具有明显的异质性,表现为各种亚型,这对指导治疗决策至关重要。本研究旨在通过分析来自马来西亚队列的 934 名乳腺癌患者的转录组图谱,研究亚洲人群中是否存在不同的乳腺癌亚型。我们的研究结果表明,HR + /HER2-乳腺癌样本显示出基于免疫表型的独特聚类模式,而不符合之前在欧洲裔女性乳腺癌中报道的传统腔A-腔B范式。这表明,免疫系统的激活在亚洲 HR + /HER2- 乳腺癌中可能扮演着比以往认识到的更重要的角色。全外显子组测序对体细胞突变的分析表明,与直觉相反,HR + /HER2-样本群表现出较高的免疫评分与较低的肿瘤突变负荷、较低的同源重组缺陷评分和较少的拷贝数畸变有关,这意味着非经典肿瘤免疫途径的参与。有必要进一步研究确定这些途径的潜在机制,从而有可能开发出针对这一特定患者群体的创新免疫治疗方法。
{"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":null,"pages":null},"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}
引用次数: 0
Screening mammography performance according to breast density: a comparison between radiologists versus standalone intelligence detection 根据乳腺密度进行乳腺 X 射线筛查的效果:放射科医生与独立智能检测之间的比较
IF 7.4 1区 医学 Pub Date : 2024-04-22 DOI: 10.1186/s13058-024-01821-w
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
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.
人工智能(AI)算法对乳腺X光筛查的独立评估尚未在亚洲妇女的大型筛查队列中得到很好的证实。我们比较了放射科医生和人工智能独立检测在韩国女性中考虑乳腺密度的筛查数字乳腺X光摄影的性能。我们回顾性地纳入了 2009 年至 2020 年期间接受初次数字乳腺 X 光摄影筛查的 89,855 名韩国女性。根据国家癌症登记处的数据,筛查乳房 X 射线照相术后 12 个月内的乳腺癌是参考标准。Lunit 软件用于确定恶性肿瘤概率分数,乳腺癌检测的临界值为 10%。根据乳腺放射科医生的记录,将人工智能的性能与乳腺成像报告和数据系统的最终分类进行了比较。根据放射科医生和人工智能的评估结果,乳腺密度被分为四类(A-D)。对不同乳腺密度类别的性能指标(癌症检出率[CDR]、灵敏度、特异性、阳性预测值[PPV]、召回率和接收者工作特征曲线下面积[AUC])进行了比较。参与者的平均年龄为 43.5 ± 8.7 岁,在 12 个月内发现了 143 例乳腺癌病例。CDR(1.1/1000 次检查)和灵敏度值显示,放射科医生和人工智能结果之间没有明显差异(69.9% [95% 置信区间 [CI], 61.7-77.3] vs. 67.1% [95% CI, 58.8-74.8])。不过,人工智能算法的特异性(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])、召回率(7.1% [95% CI, 6.9-7.2] vs. 22.5% [95% CI, 22.2-22.7])和 AUC 值(0.8 [95% CI, 0.76-0.84] vs. 0.74 [95% CI, 0.7-0.78] )(所有 P <0.05)。放射科医生和基于人工智能的结果在非致密类别中表现最佳;在异质致密类别中,放射科医生的 CDR 和灵敏度更高(P = 0.059)。不过,在包括极度致密类别在内的所有类别中,基于人工智能的结果在特异性、PPV 和召回率方面始终更胜一筹。基于人工智能的软件灵敏度略低,但差异无统计学意义。不过,它在召回率、特异性、PPV 和 AUC 方面都优于放射科医生,在极致密乳腺组织方面差距最为明显。
{"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":null,"pages":null},"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}
引用次数: 0
Meeting Abstracts from the British Society of Breast Radiology annual scientific meeting 2023 英国乳腺放射学会 2023 年科学年会会议摘要
IF 7.4 1区 医学 Pub Date : 2024-04-17 DOI: 10.1186/s13058-024-01786-w

Proffered Papers

Monday 6 November 2023

1:10 PM–2:00 PM

Abstracts listed in presenting order

Dr Jean Seely1, Prof Mohamed Abdolell2,3, Dr Jennifer Payne2,3, Dr Sian Iles2,3, Dr Georgia Spear4, Dr Nisha Sharma5, Dr Laurie R. Margolies6, Dr Sylvia Heywang-Köbrunner7, Dr Toni Vomweg8

1The Ottawa Hospital, Ottawa, Canada; 2Nova Scotia Health Authority, Canada; 3Dalhousie University, Halifax, Canada; 4NorthShore HealthSystem, Evanston, United States; 5Leeds Teaching Hospital, NHS Trust, Leeds, United Kingdom; 6Mount Sinai Health System, New York, United States; 7Referenzzentrum Mammographie Munchen, Munich, Germany; 8Radiologisches Institut Dr von Essen Koblenz, Koblenz, Germany

Breast Cancer Research 2024, 26(1):O1

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.

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.

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.

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.

Dr Matthew Common1,2, Dr Pat Rohan1,2, Dr Cathal McCarthy1,2, Eithne Downey1, Dr Niamh Hambly1, Dr Neasa ní Mhuircheartaigh1, Dr Jennifer Kerr1, Prof. Colm Power1,2, Prof. Arnold Hill1,2, Dr Deirdre Duke1,2

9%)的患者出现局部复发或转移。从确诊之日起,发生事件的中位时间为 35 个月(0-144 个月)。与无肿块增强相比,肿块样增强与较少的事件发生有统计学关联(p = 0.011)。与事件发生最明显相关的因素是三阴性(TN)状态、基线磁共振成像中淋巴结数量较多和手术后(ypN)。T分期、肿瘤分级或磁共振反应模式(同心型与溃疡型)之间无明显关联:结论:在所有接受 NACT 治疗的乳腺癌患者中,28.9% 的患者在中位 35 个月后出现了不良反应。预测接受 NACT 治疗的乳腺癌患者发生不良事件的因素包括 TN 受体状态、磁共振成像无肿块增强以及淋巴结状态较高。Megan Wallace博士2、Aisha Syed博士1、Jyoti Bansal博士11英国威尔士大学医院,加的夫;2英国南威尔士教区乳腺癌研究2024,26(1):P29目的:评估磁共振成像在检测乳腺癌患者接受新辅助化疗(NACT)后残留疾病的准确性,并与已发表的文献进行比较:对2009年至2018年期间所有用于NACT监测的乳腺磁共振成像进行回顾性评估。所有患者均接受了至少五年的随访,患者年龄中位数为 48 岁(23 至 73 岁不等)。NACT MRI扫描后的报告与组织学结果进行了比较,以确定与已发表数据的准确性:结果:在 135 名患者中,有 101 名患者有足够的数据供本研究评估。76名患者(75%)的磁共振成像报告准确预测了对NACT的反应。在对治疗反应预测不准确的患者中,68%为三阴性,其余32%为HER 2阳性。(尽管磁共振成像报告对 NACT 的反应为完全反应,但仍有 34% 的患者(34%)在切除肿瘤时发现了残留疾病。MRI 显示部分反应的 57 例患者(76%)有部分组织学反应。20%的磁共振成像报告显示乳腺癌患者有残留疾病,但组织学结果显示其对 NACT 有完全反应:结论:对于检测 NACT 后的残留疾病,磁共振成像的敏感性为 90.4%,特异性为 63%,PPV 为 83.5%,NPV 为 75.7%。这一数据与现有的出版数据相符。在磁共振成像结果不准确的患者中。克莱尔-菲利皮尼博士(Claire Filippini)1、路易斯-威尔金森博士(Louise Wilkinson)1英国牛津大学医院 NHS 基金会信托基金会乳腺癌研究 2024 年,26(1):P30 乳腺癌(BC)是英国最常见的癌症类型,每 8 名女性中就有 1 人在一生中被诊断出患有乳腺癌。早期诊断可增加康复的机会,因此放射科医生必须了解乳腺癌的早期征兆,并在报告因其他原因(如 CT 肺血管造影 (CTPA))进行的成像时注意这些征兆。本次审核的第一周期于 2021 年进行;共确定了 892 名在 2011 年至 2021 年期间被诊断出患有 BC 的女性;其中 123 人在确诊前进行过包括乳房在内的 CT 扫描,其中可见 BC,且放射科医生有机会进行报告。只有 49% 的可见癌症由放射科医生报告。审计结果已报告给当地放射科团队,并于 2023 年再次进行审计。我们分析了自 2021 年以来被诊断为 BC 的 1000 名妇女的数据,这些妇女在诊断前和首次审核结果公布后都进行了 CT 检查。在这一周期中,有 57 名妇女在 CT 中发现了偶发的 BC,81% 的病例都报告了这一情况。因此,在第一轮和第二轮审核之间,放射科医生对偶发乳腺癌的识别率有了显著提高(分别为 49% 和 81%),这对癌症检测途径产生了积极影响。开放获取本文采用知识共享署名 4.0 国际许可协议进行许可,该协议允许以任何媒介或格式使用、共享、改编、分发和复制本文,但须注明原作者和出处,提供知识共享许可协议的链接,并说明是否进行了修改。本文中的图片或其他第三方材料均包含在文章的知识共享许可协议中,除非在材料的信用栏中另有说明。 对过去 7 年中转诊到本院的所有 30 岁以下患者进行回顾性分析。2.非紧急转诊以北爱尔兰癌症网络(NICAN)指南为依据,根据该指南,30 岁以下患者出现不明原因肿块并伴有/不伴有疼痛时可视为 "非紧急 "转诊。3.诊所配备一名乳腺外科职员和两名乳腺超声技师。4.主要主诉为移动性乳房肿块(± 疼痛):结论:30 岁以下的患者可在低风险乳腺门诊得到安全管理。低风险门诊允许及时复查,在绝大多数情况下,患者可放心出院:磁共振成像对乳腺癌的检测非常灵敏。虽然目前还没有关于核磁共振成像用于乳腺癌监测(BCS)的国家指导方针,但对于年轻女性、致密乳房和乳腺X线隐匿性疾病,可以考虑使用核磁共振成像。目的:评估我们的乳腺癌监测核磁共振成像的适应症,并为核磁共振成像监测的适应症和持续时间制定标准化的地方方案。方法:对接受 BCS MRI 检查的患者进行回顾性审查:方法:对 10 年内接受 BCS 磁共振成像的患者进行回顾性审查。记录临床适应症、组织病理学和复发/新发疾病的年份:10年间共发现44例患者。中位年龄为 48.4 岁,中位监测时间为 2.7 年。最常见的适应症是隐匿性疾病。8/44(18%)例患者从磁共振成像监测中被召回进行评估。3人无需进一步干预。其中 5 人接受了活组织检查。2/5为磁共振成像检测到的复发/新发疾病&gt; 3年磁共振成像BCS。3/5为良性/B3.另有4例复发分别在第3、5、8、14年出现症状,6例复发的组织病理学检查显示2例为ILC,4例为IDC:结论:以乳腺X线隐匿性疾病为指征的复发/新发疾病比例最高。83.3%的癌症是在诊断后3年发现的,因此磁共振BCS的潜在益处与乳腺X光检查的标准相同。肿瘤类型、年龄和家族史可能会影响BCS磁共振成像的资格,需要进一步研究以统一指导原则。Neelam Soni博士1、Asha Eleti博士11英国Southend-on-sea,Southend大学医院放射科、Mid and South Essex NHS信托基金Breast Cancer Research 2024,26(1):P6目的:比较并准确描述高危乳腺癌妇女乳房X光检查、核磁共振成像和超声检查的病变特征,以早期发现癌症:方法:从过去 5 年的高危乳腺癌筛查妇女(249 人)中获取回顾性数据。共有 40 个病例在筛查乳房 X 线造影/MRI 中发现了问题,被召回进行三重评估并纳入研究。不包括建议每年例行召回的妇女。所有影像学检查结果均按照标准化的 5 分制进行评分,并与组织病理学结果进行对比:平均年龄为 45.1 岁,60% 患有 BRCA 1,32.5% 患有 BRCA 2,5% 患有 PALB2,2.5% 患有 TP53。37.5%的患者通过磁共振成像筛查,22.5%的患者通过乳房X光检查。组织病理学显示,25%的乳房 X 光检查(M3)、55%的超声检查(U3)和 30%的核磁共振检查(MRI3)发现的不确定病变为恶性。在超声波检查中,恶性病变通常呈环状(52.5%),而不是典型的棘状(15%)或微球状(12.5%)。此外,只有 20% 的病灶呈反平行方向。在核磁共振成像中,大多数病灶周界清晰(40%),12.5%无肿块增强。由于乳腺实质极为致密,核磁共振成像中40%的不确定病灶和可疑病灶在乳房X光检查中正常。此外
{"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":"<p><b>Proffered Papers</b></p><p><b>Monday 6 November 2023</b></p><p><b>1:10 PM–2:00 PM</b></p><p><i>Abstracts listed in presenting order</i></p><h3>Dr Jean Seely<sup>1</sup>, Prof Mohamed Abdolell<sup>2,3</sup>, Dr Jennifer Payne<sup>2,3</sup>, Dr Sian Iles<sup>2,3</sup>, Dr Georgia Spear<sup>4</sup>, <b><u>Dr Nisha Sharma</u></b>\u0000<sup>5</sup>, Dr Laurie R. Margolies<sup>6</sup>, Dr Sylvia Heywang-Köbrunner<sup>7</sup>, Dr Toni Vomweg<sup>8</sup>\u0000</h3><h4>\u0000<sup>1</sup>The Ottawa Hospital, Ottawa, Canada; <sup>2</sup>Nova Scotia Health Authority, Canada; <sup>3</sup>Dalhousie University, Halifax, Canada; <sup>4</sup>NorthShore HealthSystem, Evanston, United States; <sup>5</sup>Leeds Teaching Hospital, NHS Trust, Leeds, United Kingdom; <sup>6</sup>Mount Sinai Health System, New York, United States; <sup>7</sup>Referenzzentrum Mammographie Munchen, Munich, Germany; <sup>8</sup>Radiologisches Institut Dr von Essen Koblenz, Koblenz, Germany</h4><p><i>Breast Cancer Research</i> 2024, <b>26(1)</b>:O1</p><p>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.</p><p>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.</p><p>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.</p><p>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.</p><h3>\u0000<b><u>Dr Matthew Common</u></b>\u0000<sup>1,2</sup>, Dr Pat Rohan<sup>1,2</sup>, Dr Cathal McCarthy<sup>1,2</sup>, Eithne Downey<sup>1</sup>, Dr Niamh Hambly<sup>1</sup>, Dr Neasa ní Mhuircheartaigh<sup>1</sup>, Dr Jennifer Kerr<sup>1</sup>, Prof. Colm Power<sup>1,2</sup>, Prof. Arnold Hill<sup>1,2</sup>, Dr Deirdre Duke<sup>1,2</sup>\u0000</h3><h4>\u0000<sup>","PeriodicalId":9222,"journal":{"name":"Breast Cancer Research","volume":null,"pages":null},"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}
引用次数: 0
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 多中心队列研究:根据磁共振成像反应进行前哨节点活检的结果与新辅助系统疗法后 cN1-3 乳腺癌亚型的关系
IF 7.4 1区 医学 Pub Date : 2024-04-17 DOI: 10.1186/s13058-024-01807-8
Soong June Bae, Jung Whan Chun, Sae Byul Lee, Jai Min Ryu, Seok Jin Nam, Joon Jeong, Hyung Seok Park, Sung Gwe Ahn
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.
这项研究探讨了在新辅助全身疗法(NAST)后对最初结节负荷较高的患者进行前哨淋巴结活检(SLNB)的可行性。在多中心回顾性队列中,共纳入了 388 例 cN1-3 乳腺癌患者,这些患者接受了 NAST 并进行了 SLNB,随后完成了腋窝淋巴结清扫。在外部验证队列中,纳入了267名符合类似纳入标准的HER2+或三阴性乳腺癌(TNBC)患者。主要结果是根据 MRI 反应和亚型确定 SLNB 的假阴性率 (FNR)。我们将完全MRI反应者定义为NAST后乳腺和腋窝可疑特征消失的患者。在多中心回顾性队列中,388 例患者中有 130 例(33.5%)为 cN2-3 型,388 例患者中有 55 例(14.2%)表现出完全的 MRI 反应。在激素受体阳性的HER2-(n = 207)患者中,完全和非完全应答者的FNR较高(分别为31.3% [95% CI 8.6-54.0]和20.9% [95% CI 14.1-27.6])。然而,在HER2+或TNBC(n = 181)中,MRI完全应答者的FNR为0%(95% CI 0-0),而非完全应答者的FNR为33.3%(95% CI 20.8-45.9)。当我们在 HER2+ 或 TNBC(n = 267)外部队列(其中 34.2% 为 cN2-3)中验证我们的研究结果时,完全反应者的 FNR 为 7.1%(95% CI 0-16.7)。我们的研究结果表明,SLNB 可以作为对 NAST 反应良好的特定患者进行结节状态评估的可靠选择,尤其是在 MRI 反应完全的 HER2+ 和 TNBC 患者中。
{"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":null,"pages":null},"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}
引用次数: 0
Selective omission of sentinel lymph node biopsy in mastectomy for ductal carcinoma in situ: identifying eligible candidates 乳腺导管原位癌切除术中选择性省略前哨淋巴结活检:确定符合条件的候选者
IF 7.4 1区 医学 Pub Date : 2024-04-12 DOI: 10.1186/s13058-024-01816-7
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
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.
前哨淋巴结活检(SLNB)适用于接受乳房切除术的乳腺导管原位癌(DCIS)患者,这是因为考虑到乳房切除术后 SLNB 的上行分期和技术难度。然而,考虑到 DCIS 的良好预后和去升级趋势,这可能会导致潜在的过度治疗。有关这些患者上行分期和腋窝淋巴结转移的数据仍然有限。我们回顾性研究了2010年1月至2021年12月期间在江南 Severance 医院接受乳房切除术并行 SLNB 或腋窝淋巴结清扫术的 DCIS 患者。为了探讨省略 SLNB 的可行性,我们评估了 DCIS 升级为浸润癌和腋窝淋巴结转移的比率。我们进行了二元 Cox 回归分析,以确定与升期和腋窝淋巴结转移相关的临床病理因素。在385名患者中,164人(42.6%)经历了浸润癌升级:分别有53人(13.8%)、97人(25.2%)和14人(3.6%)证实为微小浸润、pT1和pT2。17例(4.4%)患者有腋窝淋巴结转移。多变量分析发现,年龄小于 50 岁(调整后的比值比 [OR],12.73;95% 置信区间 [CI],1.18-137.51;P = 0.036)和放射学评估发现可疑腋窝淋巴结(调整后的比值比 [OR],9.31;95% 置信区间 [CI],2.06-41.99;P = 0.004)是腋窝淋巴结转移的独立相关因素。在年龄大于50岁和/或无可疑腋窝淋巴结的患者中,仅有1.7%-2.3%发生了腋窝淋巴结转移。虽然在接受乳房切除术的DCIS患者中,侵袭性成分的低估率相对较高,但腋窝淋巴结转移却很少见。我们的研究结果表明,对于 50 岁以上和/或在放射学评估中没有可疑腋窝淋巴结的患者,省略 SLNB 是可行的。
{"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":null,"pages":null},"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}
引用次数: 0
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 代谢组学辅助转录组学分析揭示与 HER2 + 乳腺癌 TCbHP 方案新辅助治疗反应相关的代谢特征和潜在生物标志物
IF 7.4 1区 医学 Pub Date : 2024-04-12 DOI: 10.1186/s13058-024-01813-w
Ningning Zhang, Yuxin Huang, Guanwen Wang, Yimei Xiang, Zhouhong Jing, Junjie Zeng, Feng Yu, Xianjun Pan, Wenqi Zhou, Xiaohua Zeng
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.
本研究旨在探索与HER2+乳腺癌(BrCa)患者TCbHP方案(紫杉类药物、卡铂、曲妥珠单抗和百妥珠单抗)新辅助疗效相关的潜在指标。研究人员前瞻性地收集了40名HER2+乳腺癌患者在采用TCbHP方案进行新辅助治疗(NAT)的三个疗程中的120份血浆样本。根据 LC-MS 和 GC-MS 数据对血清代谢物进行了分析。随机森林用于建立基于治疗前差异表达代谢物的预测模型。时间序列分析用于获得治疗反应的潜在监测指标。对九份可用的治疗前核心针活检标本进行了转录组分析。还对这九名患者进行了代谢组学和转录组学的综合分析。采用 qRT-PCR 技术检测曲妥珠单抗敏感细胞系和曲妥珠单抗耐药细胞系中发生改变的基因。21名患者获得了pCR,19名患者未获得pCR。治疗前和治疗期间的血浆代谢谱存在明显差异。在基线时,pCR 患者和非 CR 患者之间共发现了 100 种不同的代谢物;这些代谢物在 40 种代谢途径中明显富集。从单一潜在代谢物[槐糖、N-(2-乙酰氨基)亚氨基二乙酸、牛磺酸和 6-羟基-2-氨基己酸]或这些代谢物的组合的 NAT 中区分 pCR 组和非 pCR 组的曲线下面积 (AUC) 值大于 0.910。18 种代谢物显示出监测疗效的潜力。一些经过验证的基因可能与曲妥珠单抗耐药性有关。39种改变的通路在转录和代谢水平上都有异常表达。血清代谢组学可作为一种强大的工具,用于探索预测或监测疗效的信息生物标志物。代谢组学与转录组学分析相结合,可以帮助人们对生化病理生理学有新的认识,并可能促进为不敏感患者开发新的治疗靶点。
{"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":null,"pages":null},"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}
引用次数: 0
Chitin-mediated blockade of chitinase-like proteins reduces tumor immunosuppression, inhibits lymphatic metastasis and enhances anti-PD-1 efficacy in complementary TNBC models 甲壳素介导的甲壳素酶样蛋白阻断剂可减少肿瘤免疫抑制、抑制淋巴转移并增强 TNBC 互补模型中抗 PD-1 的疗效
IF 7.4 1区 医学 Pub Date : 2024-04-11 DOI: 10.1186/s13058-024-01815-8
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
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.
几丁质酶样蛋白(CLPs)在癌症等炎症条件下的免疫抑制中发挥着关键作用。CLPs 没有酶活性,与天然配体几丁质结合后会被中和,从而可能减少 CLP 驱动的免疫抑制。我们利用互补小鼠模型研究了甲壳素治疗三阴性乳腺癌(TNBC)的疗效。我们还评估了甲壳素对免疫检查点阻断(ICB)的免疫调节影响,并比较了甲壳素作为通用CLP阻断剂与阻断单一CLP(即甲壳素酶3样1(CHI3L1))的功效。向雌性 BALB/c 小鼠腹腔内注射表达荧光素酶的 4T1 或 66cl4 细胞,并用几丁质联合或不联合抗程序性死亡(PD)-1 ICB 进行全身治疗。对于单一的CLP阻断,则用抗CHI3L1抗体处理肿瘤小鼠。通过生物发光成像监测转移进展。通过流式细胞术、免疫组化、细胞因子分析和 RNA 序列分析研究了原发性肿瘤和淋巴器官(即腋窝淋巴结和脾脏)中免疫细胞的变化。对 CHI3L1 刺激的 RAW264.7 巨噬细胞进行了二维淋巴内皮细胞粘附和三维淋巴整合体外试验,以研究巨噬细胞介导的淋巴重塑。甲壳素通过减少源自肿瘤相关中性粒细胞(TANs)和Stat3信号转导的CLPs的大量产生,明显降低了基于4T1模型的原发性肿瘤的进展,显著影响了CHI3L1和CHI3L3原发性肿瘤的水平。它减少了免疫抑制细胞类型,增加了原发性肿瘤和腋窝淋巴结中的抗肿瘤 T 细胞。在基于66cl4的模型中,甲壳素还能明显降低CHI3L3原发肿瘤水平和免疫抑制。与抗CHI3L1相比,甲壳素增强了原发性肿瘤生长抑制和抗肿瘤性。两种治疗方法都同样抑制了巨噬细胞的淋巴粘附和整合,从而阻碍了淋巴肿瘤细胞的扩散。在 ICB 联合疗法中,甲壳素减轻了两种 TNBC 模型的抗 PD-1 抗性,与甲壳素单药疗法相比,甲壳素可显著减少原发性肿瘤和肺转移生长。这些附加效应是通过原发性肿瘤和淋巴器官中 CD8α+ T 细胞浸润和活化的额外增加而产生的。甲壳素作为一种通用的CLP阻断剂,可以减少CLP的产生,增强抗肿瘤免疫以及ICB反应,从而支持其在免疫抑制的TNBC患者中的潜在临床意义。
{"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":null,"pages":null},"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}
引用次数: 0
Serum protein profiling reveals an inflammation signature as a predictor of early breast cancer survival 血清蛋白图谱显示炎症特征可预测早期乳腺癌的生存率
IF 7.4 1区 医学 Pub Date : 2024-04-09 DOI: 10.1186/s13058-024-01812-x
Peeter Karihtala, Suvi-Katri Leivonen, Ulla Puistola, Elina Urpilainen, Anniina Jääskeläinen, Sirpa Leppä, Arja Jukkola
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.
乳腺癌在生物学、免疫学和预后方面表现出相当大的异质性。目前,还没有基于血清蛋白的有效工具来评估早期乳腺癌患者的预后。研究对象包括 521 名早期乳腺癌患者,中位随访时间为 8.9 年。此外,还有 61 名乳腺纤维腺瘤或非典型性导管增生患者作为对照。我们使用近距离延伸测定法来测量术前血清中 92 种与炎症和免疫反应过程相关的蛋白质水平。浸润性癌症被随机分为发现组(n = 413)和验证组(n = 108)进行统计分析。通过LASSO回归,我们确定了九种蛋白特征(CCL8、CCL23、CCL28、CSCL10、S100A12、IL10、IL10RB、STAMPB2和TNFβ),它们比传统预后因素更准确地预测了各种生存终点。在随时间变化的分析中,该模型的预后能力随时间变化保持稳定。我们还开发并验证了一个 17 蛋白模型,该模型具有区分乳腺良性病变和恶性病变的潜力(Wilcoxon p < 2.2*10- 16;AUC 0.94)。炎症和免疫相关血清蛋白有可能超越早期乳腺癌的传统预后因素。它们还有助于区分良性和恶性乳腺病变。
{"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":null,"pages":null},"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}
引用次数: 0
U2AF2-SNORA68 promotes triple-negative breast cancer stemness through the translocation of RPL23 from nucleoplasm to nucleolus and c-Myc expression U2AF2-SNORA68通过RPL23从核质到核仁的易位和c-Myc的表达促进三阴性乳腺癌干性的形成
IF 7.4 1区 医学 Pub Date : 2024-04-09 DOI: 10.1186/s13058-024-01817-6
Wenrong Zhang, Xinyue Song, Zining Jin, Yiqi Zhang, Shan Li, Feng Jin, Ang Zheng
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.
小核RNA(snoRNA)在核糖体生物合成中发挥着关键作用。然而,snoRNA调控癌症干性的机制仍有待全面阐明。通过原位杂交和 qRT-PCR 技术评估了 SNORA68 在乳腺癌组织中的表达。增殖、迁移、凋亡和干性分析用于确定 SNORA68 在癌变和干性维持中的作用。从机制上讲,进行了 RNA 拉取、RNA 免疫沉淀(RIP)、细胞分馏和共免疫沉淀试验。SNORA68在三阴性乳腺癌(TNBC)中高表达,并与肿瘤大小(P = 0.048)、ki-67水平(P = 0.037)和TNM分期(P = 0.015)显著相关。临床获益患者的血浆 SNORA68 浓度明显较低。SNORA68高的患者无病生存期(DFS)明显较短(P = 0.036)。研究发现,SNORA68在体外和体内可促进TNBC的细胞干性和癌变。此外,SNORA68表达升高导致核仁RPL23表达增加,并通过结合U2AF2将RPL23保留在核仁中。核仁中的 RPL23 随后会上调 c-Myc 的表达。这一途径通过异种移植模型得到了验证。U2AF2-SNORA68通过将RPL23保留在核仁中并增加c-Myc的表达来促进TNBC干性,这为干性的调控机制提供了新的见解。
{"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":null,"pages":null},"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}
引用次数: 0
Clinical factors associated with patterns of endocrine therapy adherence in premenopausal breast cancer patients 绝经前乳腺癌患者坚持内分泌治疗模式的相关临床因素
IF 7.4 1区 医学 Pub Date : 2024-04-08 DOI: 10.1186/s13058-024-01819-4
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
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.
激素受体阳性乳腺癌患者被建议接受至少五年的辅助内分泌治疗,但这种治疗的依从性往往不尽如人意。我们调查了绝经前乳腺癌患者坚持辅助内分泌治疗(AET)的纵向趋势,并确定了与坚持AET治疗相关的临床特征,包括基线合并症和非癌症慢性药物使用。我们纳入了 2002-2011 年期间确诊并在丹麦乳腺癌组临床数据库中登记的 I-III 期绝经前乳腺癌患者,这些患者都开始接受 AET 治疗。我们采用基于群体的轨迹模型来描述 AET 的依从性模式。我们还将患者与丹麦人口登记进行了关联,并拟合了多叉逻辑模型,以计算临床特征与 AET 依从模式相关的几率比 (OR) 和 95% 置信区间 (95%CI)。我们在 4353 名女性中发现了三种依从模式--高度依从者(57%)、缓慢依从者(36%)和快速依从者(6.9%)。患有 I 期疾病(vs. II 期;OR:1.9,95% CI 1.5,2.5)、未接受化疗(vs. 化疗;OR:4.3,95% CI 3.0,6.1)、患有流行性合并症(Charlson 合并症指数评分≥ 1 vs. 0;OR:1.6,95% CI 3.0,6.1)的女性。0;OR:1.6,95% CI 1.1,2.3),以及有长期非癌症用药史(vs. 无;OR:1.3,95% CI 1.0,1.8)的女性与高度依从者相比,更有可能快速减药。癌症 I 期、未接受化疗、合并症负担较重以及有长期非抗癌药物使用史的妇女较少坚持 AET。采取措施提高这些妇女群体的依从性可能会降低她们的复发风险。
{"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":null,"pages":null},"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}
引用次数: 0
期刊
Breast Cancer Research
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1