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Prospective study of once-daily accelerated partial breast irradiation using 3-dimensional conformal external beam radiotherapy for Japanese women: 12-year outcomes, toxicity, and cosmesis. 日本女性每日一次加速部分乳房放射治疗使用三维适形外束放疗的前瞻性研究:12年的结果、毒性和美容。
IF 4 3区 医学 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2025-01-01 Epub Date: 2024-12-04 DOI: 10.1007/s12282-024-01650-x
Kana Takahashi, Yoshikazu Kagami, Ryoichi Yoshimura, Madoka Morota, Naoya Murakami, Satoshi Nakamura, Hiroyuki Okamoto, Ayaka Nagao, Madoka Sakuramachi, Tairo Kashihara, Tomoya Kaneda, Koji Inaba, Kae Okuma, Yuko Nakayama, Jun Itami, Hiroshi Igaki

Background: To analyze in a prospective study the long-term safety and efficacy of 3-dimensional conformal radiotherapy (3D-CRT) to deliver accelerated partial breast irradiation (APBI) for Japanese women with early breast cancer.

Methods: Breast cancer patients with pathological tumor size ≤ 3 cm, age ≥ 20 years, lumpectomy with at least a 5 mm margin, and ≤ 3 positive axillary nodes were eligible. APBI was delivered by 3D-CRT at a dose of 38.5 Gy in 10 fractions over 10 days. The primary endpoints were the frequency and severity of acute and late radiation toxicities, and secondary endpoints were local control, survival, and cosmesis. The sample size was determined based on the incidence of ≥ grade 3 acute and late radiation toxicities, which required 71 enrollments.

Results: Between 2008 and 2010, 73 patients enrolled in this trial. Twelve patients (16%) had 1-3 lymph node metastases. At a median follow-up of 12.6 years (range: 2.7-13.9 years), there were no cases of grade ≥ 3 acute or late toxicity. There were 4 ipsilateral breast tumor recurrence (IBTR) events: 12-year IBTR incidence was 4.4%. The difference in the incidence of IBTR between node-negative and node-positive patients was marginal (1.9% vs. 16.7%, p = 0.055). The majority of patients (94.4% at 2 years, 89.3% at 10 years after enrollment) had excellent/good cosmesis.

Conclusions: APBI delivered with 3D-CRT is a feasible treatment option for Asian females, but it was indicated that node-positive status might increase IBTR risk.

背景:在一项前瞻性研究中分析三维适形放疗(3D-CRT)对日本早期乳腺癌妇女进行加速部分乳房照射(APBI)的长期安全性和有效性。方法:病理肿瘤大小≤3cm,年龄≥20岁,乳房肿瘤切除≥5mm切缘,≤3个腋窝淋巴结阳性的乳腺癌患者。APBI通过3D-CRT以38.5 Gy的剂量分10次递送,持续10天。主要终点是急性和晚期放射毒性的频率和严重程度,次要终点是局部控制、生存和修复。样本量是根据≥3级急性和晚期放射毒性的发生率确定的,需要71个受试者。结果:2008年至2010年间,73名患者参加了该试验。12例(16%)患者有1-3个淋巴结转移。在中位随访12.6年(范围:2.7-13.9年),没有出现≥3级急性或晚期毒性的病例。有4例同侧乳腺肿瘤复发(IBTR)事件:12年IBTR发生率为4.4%。淋巴结阴性和淋巴结阳性患者的IBTR发病率差异很小(1.9% vs. 16.7%, p = 0.055)。大多数患者(入组2年后94.4%,入组10年后89.3%)具有良好的美容效果。结论:APBI联合3D-CRT是亚洲女性可行的治疗选择,但淋巴结阳性可能增加IBTR风险。
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引用次数: 0
Clinical outcomes after post-operative radiotherapy for breast cancer patients presenting with ipsilateral supraclavicular metastasis: considerations on the cranial border of irradiation field. 同侧锁骨上转移的乳腺癌患者术后放疗后的临床疗效:对照射区域颅骨边界的考虑。
IF 4 3区 医学 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2025-01-01 Epub Date: 2024-10-23 DOI: 10.1007/s12282-024-01644-9
Xiaofang Wang, Xiaomeng Zhang, Li Zhang, Jin Meng, Wei Shi, Xingxing Chen, Zhaozhi Yang, Xin Mei, Xiaoli Yu, Zhen Zhang, Zhimin Shao, Xiaomao Guo, Jinli Ma

Background: Disease recurrence at lower neck adjacent to ipsilateral supraclavicular (SCV) region represents a concern in locally advanced breast cancer patients presenting with SCV metastasis at diagnosis. This study aims to report the outcomes following post-operative radical radiation therapy and discuss the reasonable cranial border of the irradiation field for N3c patients.

Methods: Between July 2016 and January 2022, a total of 268 patients were eligible for analysis. The endpoints included in-field and out-field cervical failures, local-regional recurrence-free survival (LRRFS), SCV recurrence-free survival (SRFS), distant metastasis-free survival (DMFS), relapse-free survival (RFS), and overall survival (OS).

Results: During a median follow-up of 37 months (range 3-89 months), 17 patients (6.3%) developed local-regional recurrence as the first recurrence event, with 13 having concomitant distant-metastasis (DM); 56 patients (20.9%) had DM alone. The 3-year rates of LRRFS, SRF, DMFS, RFS, and OS were 92.3%, 94.5%, 74.5%, 73.0%, and 90.0%, respectively. 89.2% of patients received RT with the cranial border at the top of hyoid bone, and 95.1% of patients received a boost not exceeding the level of cricoid cartilage. A total of 11 patients (4.1%) developed ipsilateral SCV failure, and 3 patients (1.1%) experienced cervical failure, including 2 in-field failures and 1 out-field failure. Neoadjuvant systemic therapy (NST) was administered to 234 patients (87.3%). In the multivariate analysis, non-ypN0, triple-negative subtype and cT4 at diagnosis were predictors of worse SRFS and RFS in NST subgroup.

Conclusion: Our findings suggest that radical RT with cranial border of irradiation field at the hyoid bone level lead to excellent local-regional control, and out-field cervical failure was rare. The irradiation field might not extend to mastoid process.

背景:同侧锁骨上区(SCV)邻近的下颈部疾病复发是局部晚期乳腺癌患者诊断时出现锁骨上区转移的一个问题。本研究旨在报告术后根治性放疗的结果,并探讨N3c患者照射野的合理颅缘:方法:2016年7月至2022年1月期间,共有268名患者符合分析条件。终点包括场内和场外宫颈癌失败率、无局部区域复发生存率(LRRFS)、无SCV复发生存率(SRFS)、无远处转移生存率(DMFS)、无复发生存率(RFS)和总生存率(OS):在中位 37 个月(3-89 个月)的随访期间,17 名患者(6.3%)首次复发为局部区域复发,其中 13 名患者伴有远处转移(DM);56 名患者(20.9%)仅有 DM。3年的LRRFS、SRF、DMFS、RFS和OS率分别为92.3%、94.5%、74.5%、73.0%和90.0%。89.2%的患者接受了以舌骨顶部为颅缘的 RT,95.1%的患者接受了不超过环状软骨水平的增强。共有11名患者(4.1%)出现同侧SCV失败,3名患者(1.1%)出现颈部失败,其中包括2例场内失败和1例场外失败。234名患者(87.3%)接受了新辅助系统治疗(NST)。在多变量分析中,非ypN0、三阴亚型和诊断时的cT4是NST亚组SRFS和RFS较差的预测因素:我们的研究结果表明,以舌骨水平为照射野头颅边界的根治性RT可取得良好的局部区域控制效果,而照射野外的颈椎衰竭则很少见。照射野可能不会延伸至乳突。
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引用次数: 0
Local recurrence and residual tumor rates following cryoablation for small early-stage breast cancers: systemic review and meta-analysis. 早期小型乳腺癌冷冻消融术后的局部复发率和残留肿瘤率:系统回顾和荟萃分析。
IF 4 3区 医学 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2025-01-01 Epub Date: 2024-10-19 DOI: 10.1007/s12282-024-01643-w
Eelin Tan, Jingli Chong, Uei Pua, Ern Yu Tan, Wing Yan Mok

Background: Cryoablation is currently being investigated as a minimally invasive alternative to breast-conserving surgery. This meta-analysis investigates the local recurrence and residual tumor rates after cryoablation for small early-stage breast cancers.

Methods: A systematic search was conducted on Embase, PubMed, Google Scholar, and the International Clinical Trials Registry Platform from inception to 16 June 2024. Studies of patients with breast cancers ≤ 20 mm treated with cryoablation only or cryoablation followed by surgery were included. Pooled local recurrence rates (cryoablation only) and pooled residual tumors rates (cryoablation followed by surgery) were estimated with mixed-effects models. Between-study heterogeneity was assessed using I2 statistics. Where I2 exceeded 50%, outlier and influence analysis, followed by sensitivity analysis excluding outliers, were conducted.

Results: Twelve studies met inclusion criteria, of which 7 studies (530 female patients, 531 breast tumors) reported on patients treated with cryoablation only and 5 studies (220 female patients, 222 breast tumors) reported on patients treated with cryoablation followed by surgery. For studies on cryoablation only, pooled local recurrence rate was 1.1% (95% CI 0.42-3.03%) with low between-study heterogeneity (I2 value = 0%; 95% CI 0.0-70.8%; p = 0.95). For studies on cryoablation followed by surgery, pooled residual tumor rate was 12.0% (95% CI 3.85-31.64%); however, substantial between-study heterogeneity (I2 value = 76.1%; 95% CI 41.7-90.2%; p < 0.01) was present. Influence analysis revealed 1 outlier study. When this study was excluded, pooled residual tumor rate was 8.2% (95% CI 3.84-16.68%) with improvement in heterogeneity (I2 value = 0%; 95% CI 0.0-84.7%; p = 0.64).

Conclusion: Pooled local recurrence and residual tumor rates after cryoablation are comparable to local recurrence rates after breast-conserving therapy and re-excision rates following breast-conserving surgery, respectively. These results are encouraging but should be interpreted with caution due to lack of comparative studies.

背景:冷冻消融术目前正作为保乳手术的微创替代方法接受研究。这项荟萃分析调查了早期乳腺癌患者冷冻消融术后的局部复发率和肿瘤残留率:方法:在Embase、PubMed、Google Scholar和国际临床试验注册平台(International Clinical Trials Registry Platform)上进行了系统检索。方法:在Embase、PubM、Google学术和国际临床试验注册平台上进行了系统性检索,检索时间为2024年6月16日。采用混合效应模型估算了汇总的局部复发率(仅冷冻消融)和汇总的残留肿瘤率(冷冻消融后再手术)。研究间异质性采用I2统计量进行评估。当I2超过50%时,进行离群值和影响分析,然后进行排除离群值的敏感性分析:12项研究符合纳入标准,其中7项研究(530名女性患者,531颗乳腺肿瘤)仅报告了接受冷冻消融治疗的患者,5项研究(220名女性患者,222颗乳腺肿瘤)报告了接受冷冻消融治疗后再进行手术的患者。对于仅进行冷冻消融的研究,汇总的局部复发率为 1.1%(95% CI 0.42-3.03%),研究间异质性较低(I2 值 = 0%;95% CI 0.0-70.8%;P = 0.95)。对于冷冻消融后再手术的研究,汇总的残留肿瘤率为12.0%(95% CI 3.85-31.64%);然而,研究间异质性很大(I2值=76.1%;95% CI 41.7-90.2%;P 2值=0%;95% CI 0.0-84.7%;P = 0.64):结论:冷冻消融术后的汇总局部复发率和残留肿瘤率分别与保乳治疗后的局部复发率和保乳手术后的再次切除率相当。这些结果令人鼓舞,但由于缺乏对比研究,在解释这些结果时应谨慎。
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引用次数: 0
Liquid biopsy for breast cancer and other solid tumors: a review of recent advances. 乳腺癌和其他实体瘤的液体活检:最新进展综述。
IF 4 3区 医学 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2025-01-01 Epub Date: 2024-03-16 DOI: 10.1007/s12282-024-01556-8
Hirofumi Ohmura, Fumiyasu Hanamura, Yuta Okumura, Yuki Ando, Takaaki Masuda, Koshi Mimori, Koichi Akashi, Eishi Baba

Liquid biopsy using circulating tumor DNA (ctDNA) has been reported to be less invasive and effective for comprehensive genetic analysis of heterogeneous solid tumors, including decision-making for therapeutic strategies, predicting recurrence, and detecting genetic factors related to treatment resistance in various types of cancers. Breast cancer, colorectal cancer, and lung cancer are among the most prevalent malignancies worldwide, and clinical studies of liquid biopsy for these cancers are ongoing. Liquid biopsy has been used as a companion diagnostic tool in clinical settings, and research findings have accumulated, especially in cases of colorectal cancer after curative resection and non-small cell lung cancer (NSCLC) after curative chemoradiotherapy, in which ctDNA detection helps predict eligibility for adjuvant chemotherapy. Liquid biopsy using ctDNA shows promise across a wide range of cancer types, including breast cancer, and its clinical applications are expected to expand further through ongoing research. In this article, studies on liquid biopsy in breast cancer, colorectal cancer, and NSCLC are compared focusing on ctDNA.

据报道,利用循环肿瘤 DNA(ctDNA)进行液体活检创伤较小,而且能有效地对异质性实体瘤进行全面的遗传分析,包括决策治疗策略、预测复发以及检测与各类癌症耐药性有关的遗传因素。乳腺癌、结肠直肠癌和肺癌是全球发病率最高的恶性肿瘤,针对这些癌症的液体活检临床研究正在进行中。液体活检已被用作临床辅助诊断工具,并积累了大量研究成果,特别是在治愈性切除术后的结直肠癌和治愈性化疗放疗后的非小细胞肺癌(NSCLC)病例中,ctDNA 检测有助于预测辅助化疗的资格。利用ctDNA进行的液体活检在包括乳腺癌在内的多种癌症类型中都显示出了前景,其临床应用有望通过正在进行的研究进一步扩大。本文将以ctDNA为重点,对乳腺癌、结直肠癌和NSCLC的液体活检研究进行比较。
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引用次数: 0
An insight into the role of innate immune cells in breast tumor microenvironment. 深入了解先天性免疫细胞在乳腺肿瘤微环境中的作用。
IF 4 3区 医学 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2025-01-01 Epub Date: 2024-10-26 DOI: 10.1007/s12282-024-01645-8
Sandini Garg, Garima Rai, Sakshi Singh, Pammi Gauba, Javed Ali, Shweta Dang

The immune background of breast cancer is highly heterogeneous and the immune system of the human body plays a dual role by both promoting and suppressing its progression. Innate immune cells are the first line of defense in the immune system and impart protection by identifying and interacting with foreign pathogens and cancer cells. Different innate immune cells like natural killer cells, macrophages, dendritic cells, and myeloid suppressor cells take part in hosting the cancer cells. Autophagy is another key component inside the tumor microenvironment and is linked to the disintegration and recycling of cellular components. Within the tumor microenvironment autophagy is involved with Pattern Recognition Receptors and inflammation. Various clinical studies have shown prominent results where innate immune cells and autophagy in combination are used for pathogen as well as cancer cell clearance. However, it is necessary to comprehend the complex tumor microenvironment so that different therapeutic approaches can be developed to enhance the suppressive actions of the cells toward breast cancer cells. In this review article, the complex interaction between immune cells and breast cancer cells and their role in developing effective immunotherapies to improve patient outcomes are discussed in detail.

乳腺癌的免疫背景是高度异质性的,人体的免疫系统扮演着双重角色,既促进又抑制乳腺癌的发展。先天性免疫细胞是免疫系统的第一道防线,通过识别外来病原体和癌细胞并与之相互作用来提供保护。不同的先天性免疫细胞,如自然杀伤细胞、巨噬细胞、树突状细胞和骨髓抑制细胞,都参与了对癌细胞的收容。自噬是肿瘤微环境中的另一个关键组成部分,与细胞成分的分解和再循环有关。在肿瘤微环境中,自噬与模式识别受体和炎症有关。多项临床研究表明,先天性免疫细胞和自噬作用结合使用可清除病原体和癌细胞,效果显著。然而,我们有必要了解复杂的肿瘤微环境,从而开发出不同的治疗方法来增强自噬细胞对乳腺癌细胞的抑制作用。在这篇综述文章中,我们将详细讨论免疫细胞与乳腺癌细胞之间复杂的相互作用,以及它们在开发有效免疫疗法以改善患者预后方面的作用。
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引用次数: 0
Prospects for liquid biopsy using microRNA and extracellular vesicles in breast cancer. 利用微RNA和细胞外囊泡进行乳腺癌液体活检的前景。
IF 4 3区 医学 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2025-01-01 Epub Date: 2024-03-30 DOI: 10.1007/s12282-024-01563-9
Takahiro Ochiya, Kazuki Hashimoto, Akihiko Shimomura

Among the analytes circulating in body fluids, microRNAs, a type of non-coding RNA and known to exist 2655 in primates, have attracted attention as a novel biomarker for cancer screening. MicroRNAs are signaling molecules with important gene expression regulatory functions that can simultaneously control many gene functions and multiple different pathways in living organisms. These microRNAs are transported in extracellular vesicles (EVs), which are lipid bilayers with 50-150 nm in diameter, and are used as communication tools between cells. Furthermore, the EVs that carry these microRNAs circulate in the bloodstream and have other important implications for understanding the pathogenesis and diagnosis of breast cancer. The greatest benefit from cancer screening is the reduction in breast cancer mortality rate through early detection. Other benefits include reduced incidence of breast cancer, improved quality of life, prognosis prediction, contribution to personalized medicine, and relative healthcare cost containment. This paper outlines the latest developments in liquid biopsy for breast cancer, especially focusing on microRNA and EV diagnostics.

在体液循环的分析物中,microRNA(一种非编码 RNA,已知在灵长类动物中有 2655 种)作为一种新型的癌症筛查生物标记物备受关注。microRNA 是一种信号分子,具有重要的基因表达调控功能,可同时控制生物体内的多种基因功能和多种不同途径。这些microRNA通过直径为50-150 nm的脂质双分子层--胞外囊泡(EVs)运输,被用作细胞间的通讯工具。此外,携带这些 microRNAs 的 EVs 在血液中循环,对了解乳腺癌的发病机制和诊断有其他重要意义。癌症筛查的最大益处是通过早期发现降低乳腺癌死亡率。其他益处还包括降低乳腺癌发病率、提高生活质量、预后预测、促进个性化医疗以及相对的医疗成本控制。本文概述了乳腺癌液体活检的最新进展,尤其侧重于 microRNA 和 EV 诊断。
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引用次数: 0
Comparative assessment of breast volume using a smartphone device versus MRI. 使用智能手机设备与核磁共振成像对乳房体积进行比较评估。
IF 4 3区 医学 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2025-01-01 Epub Date: 2024-11-15 DOI: 10.1007/s12282-024-01647-6
Annika S Behrens, Hanna Huebner, Lothar Häberle, Marc Stamminger, Daniel Zint, Felix Heindl, Julius Emons, Carolin C Hack, Naiba Nabieva, Michael Uder, Matthias Wetzl, Marius Wunderle, Matthias W Beckmann, Peter A Fasching, Sabine Ohlmeyer

Background: Assessment of breast volume has a relevance for aesthetic surgery and for the prevention and prediction of breast diseases. This study investigated breast volume measurements using a three-dimensional (3D) body surface scanner integrated in a smartphone device in comparison with magnetic resonance imaging (MRI) scans.

Methods: Breast volume was assessed for 22 women who underwent routine MRI imaging. 3D surface images were acquired using a smartphone's digital texture camera (iPhone 11 Pro Max, Apple, California, USA, 2019). Breast volumes were manually outlined and calculated by two independent investigators using a 3D software tool (Meshmixer 3.5, Autodesk, Inc., 2018). Volume assessments from MRI images were performed by a radiologist using Syngo.via (Siemens Healthcare, Erlangen, Germany, VB50). The agreement between both methods and the inter-observer agreement was calculated with the concordance correlation coefficients and analysed with Bland-Altman plots.

Results: The mean breast volume as determined by MRI volumetry was 771.0 ml on the left side and 763.9 ml on the right side. Utilizing the 3D body surface volume assessment method, the mean breast volume was measured as 660.3 ml (observer A) and 616.8 ml (observer B) on the left side, and 701.9 ml (observer A) and 638.6 ml (observer B) on the right side. Although a high correlation was observed, differences in volume measurements appeared more pronounced in cases of larger breast volume.

Conclusions: Smartphone-based 3D assessment of breast volume sufficiently agreed with MRI-based breast volume. This new technique could be used for cosmetic breast assessments in a surgical context and possibly in breast cancer risk studies assessing breast volume as outcome parameters.

背景:乳房体积的评估与美容手术以及乳腺疾病的预防和预测有关。本研究使用集成在智能手机设备中的三维(3D)体表扫描仪测量乳房体积,并与磁共振成像(MRI)扫描进行比较:对 22 名接受常规核磁共振成像的女性进行了乳房体积评估。使用智能手机的数字纹理相机(iPhone 11 Pro Max,苹果公司,美国加利福尼亚州,2019 年)获取三维表面图像。乳房体积由两名独立研究人员使用三维软件工具(Meshmixer 3.5,Autodesk 公司,2018 年)手动勾勒和计算。一名放射科医生使用 Syngo.via(西门子医疗,德国埃尔兰根,VB50)对核磁共振图像进行体积评估。两种方法之间的一致性和观察者之间的一致性用一致性相关系数计算,并用Bland-Altman图进行分析:核磁共振成像体积测量法确定的平均乳房体积为左侧 771.0 毫升,右侧 763.9 毫升。利用三维体表体积评估法测得的平均乳房体积为:左侧 660.3 毫升(观察者 A)和 616.8 毫升(观察者 B),右侧 701.9 毫升(观察者 A)和 638.6 毫升(观察者 B)。虽然观察到的相关性很高,但在乳房体积较大的情况下,体积测量值的差异显得更为明显:结论:基于智能手机的三维乳房体积评估与基于核磁共振成像的乳房体积评估完全一致。这项新技术可用于外科手术中的乳房美容评估,也可用于以乳房体积为结果参数的乳腺癌风险评估研究。
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引用次数: 0
Development and validation of a predictive risk tool for VTE in women with breast cancer under chemotherapy: a cohort study in China. 中国乳腺癌化疗妇女 VTE 风险预测工具的开发与验证:一项队列研究。
IF 4 3区 医学 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2025-01-01 Epub Date: 2024-11-16 DOI: 10.1007/s12282-024-01646-7
Qianjie Xu, Xiaosheng Li, Yuliang Yuan, Zuhai Hu, Guanzhong Liang, Ying Wang, Wei Zhang, Ya Liu, Wei Wang, Haike Lei

Objective: The incidence of venous thromboembolism (VTE) is significantly elevated in breast cancer patients, with a three-to-fourfold increase, and further escalates to sixfold in those undergoing chemotherapy. This study aims to identify the risk factors for VTE and develop a Nomogram risk prediction model distinct from the traditional Khorana score.

Methods: Univariate Cox regression analysis assessed the impact of each variable on the occurrence of VTE, while stepwise multivariate Cox regression analysis identified independent predictors. Based on these results, we constructed a Nomogram model. The model's performance was validated using the C-index, receiver-operating characteristic curve (ROC), calibration curves, and decision curve analysis (DCA). Comparisons were made with the Khorana score to evaluate the practical application value.

Results: Out of the 903 patients, 108 (11.96%) developed VTE. Cox regression analysis identified that Stage, undergoing surgery, age, white blood cells (WBC), D-dimer, and carcinoembryonic antigen (CEA) were significant risk factors for VTE (P < 0.05). The Nomogram model's C-index was 0.77 (95% CI 0.72-0.83) in the training set and 0.76 (95% CI 0.69-0.84) in the validation set. The model demonstrated excellent predictive accuracy and generalizability on the receiver-operating characteristic (ROC) curves and calibration curves. Compared to the traditional Khorana score, the Nomogram model showed superior predictive accuracy and greater clinical benefit.

Conclusions: This study established a VTE risk prediction model for breast cancer patients undergoing chemotherapy. The model is characterized by its intuitive and straightforward application, making it highly suitable for rapid VTE risk assessment in clinical practice.

目的:乳腺癌患者的静脉血栓栓塞症(VTE)发病率明显升高,增加了三至四倍,而接受化疗的患者的发病率则进一步上升至六倍。本研究旨在确定VTE的风险因素,并建立一个有别于传统Khorana评分的Nomogram风险预测模型:方法:单变量 Cox 回归分析评估了每个变量对 VTE 发生的影响,而逐步多变量 Cox 回归分析确定了独立的预测因素。根据这些结果,我们构建了一个 Nomogram 模型。该模型的性能通过 C 指数、接收器工作特征曲线 (ROC)、校准曲线和决策曲线分析 (DCA) 得到验证。与 Khorana 评分进行了比较,以评估其实际应用价值:在 903 名患者中,108 人(11.96%)发生了 VTE。Cox 回归分析发现,分期、接受手术、年龄、白细胞(WBC)、D-二聚体和癌胚抗原(CEA)是导致 VTE 的重要风险因素(P 结论:该研究建立了 VTE 风险预测模型,并将其与 Khorana 评分进行比较,以评估其实际应用价值:本研究为接受化疗的乳腺癌患者建立了一个 VTE 风险预测模型。该模型具有直观、简单易用的特点,非常适合在临床实践中快速评估 VTE 风险。
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引用次数: 0
Prediction model for individualized precision surgery in breast cancer patients with complete response on MRI and residual calcifications on mammography after neoadjuvant chemotherapy. 新辅助化疗后磁共振成像完全反应且乳腺造影有残留钙化的乳腺癌患者个体化精准手术的预测模型。
IF 4 3区 医学 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2025-01-01 Epub Date: 2024-09-30 DOI: 10.1007/s12282-024-01638-7
Mi-Ri Kwon, Eun Young Ko, Jeong Eon Lee, Boo-Kyung Han, Eun Sook Ko, Ji Soo Choi, Haejung Kim, Myoung Kyoung Kim, Jonghan Yu, Hyunwoo Lee, Inyoung Youn

Background: Identifying whether there is residual carcinoma in remaining suspicious calcifications after neoadjuvant chemotherapy (NAC) in breast cancer patients can provide crucial information for surgeons in determining the most appropriate surgical approach. Therefore, we investigated factors predicting calcifications without residual carcinoma (ypCalc_0) or with residual carcinoma (ypCalc_ca) and aimed to develop a prediction model for patients exhibiting residual suspicious calcifications on mammography but complete response on MRI after NAC.

Methods: This retrospective study included breast cancer patients undergoing NAC, showing residual suspicious mammographic calcifications but complete response on MRI between January 2019 and December 2020 (development set) and between January 2021 and December 2022 (validation set). Multivariable logistic regression analysis identified significant factors associated with ypCalc_0. The prediction model, developed using a decision tree and factors from logistic regression analysis, was validated in the validation set.

Results: The development set included 134 women (mean age, 50.6 years; 91 with ypCalc_0 and 43 with ypCalc_ca) and validation set included 146 women (mean age, 51.0 years; 108 with ypCalc_0 and 38 with ypCalc_ca). Molecular subtype (P = .0002) and high Ki-67 (P = .02) emerged as significant independent factors associated with ypCalc_0 in the development set. The prediction model, incorporating hormone receptor (HR)-/human epidermal growth factor receptor 2 (HER2)+ with high Ki-67 as ypCalc_0 predictors, and HR+/HER2- cancers or HR+/HER2+ or triple-negative (TN) cancers with low Ki-67, as ypCalc_ca predictors, achieved an area under receiver operating characteristic curve of 0.844 (95% CI 0.774-0.914) in the validation set.

Conclusion: Minimized surgery may be considered for managing residual calcifications in HR-/HER2+ with high Ki-67 cancers, while complete excision is recommended for HR+/HER2- breast cancers or for HR+/HER2+or TN breast cancers with low Ki-67.

背景:确定乳腺癌患者在接受新辅助化疗(NAC)后残留的可疑钙化中是否有残留癌,可为外科医生决定最合适的手术方法提供重要信息。因此,我们研究了预测无残留癌(ypCalc_0)或有残留癌(ypCalc_ca)的钙化的因素,并旨在为新辅助化疗后乳腺 X 线摄影显示残留可疑钙化但核磁共振成像显示完全反应的患者建立一个预测模型:这项回顾性研究纳入了在2019年1月至2020年12月期间(开发集)和2021年1月至2022年12月期间(验证集)接受NAC治疗的乳腺癌患者,这些患者在乳腺X光检查中显示残留可疑钙化,但在MRI检查中显示完全反应。多变量逻辑回归分析确定了与 ypCalc_0 相关的重要因素。利用决策树和逻辑回归分析中的因素建立的预测模型在验证集中得到了验证:开发集包括 134 名妇女(平均年龄 50.6 岁;91 人患有 ypCalc_0,43 人患有 ypCalc_ca),验证集包括 146 名妇女(平均年龄 51.0 岁;108 人患有 ypCalc_0,38 人患有 ypCalc_ca)。分子亚型(P = 0.0002)和高 Ki-67(P = 0.02)是开发集中与 ypCalc_0 相关的重要独立因素。预测模型将激素受体(HR)-/人表皮生长因子受体2(HER2)+和高Ki-67作为ypCalc_0的预测因子,将HR+/HER2-癌症或HR+/HER2+或三阴性(TN)癌症和低Ki-67作为ypCalc_ca的预测因子,在验证集中的接收者操作特征曲线下面积达到0.844(95% CI 0.774-0.914):结论:在处理高Ki-67的HR-/HER2+乳腺癌的残留钙化时,可考虑进行微创手术,而对于HR+/HER2-乳腺癌或低Ki-67的HR+/HER2+或TN乳腺癌,则建议进行完全切除术。
{"title":"Prediction model for individualized precision surgery in breast cancer patients with complete response on MRI and residual calcifications on mammography after neoadjuvant chemotherapy.","authors":"Mi-Ri Kwon, Eun Young Ko, Jeong Eon Lee, Boo-Kyung Han, Eun Sook Ko, Ji Soo Choi, Haejung Kim, Myoung Kyoung Kim, Jonghan Yu, Hyunwoo Lee, Inyoung Youn","doi":"10.1007/s12282-024-01638-7","DOIUrl":"10.1007/s12282-024-01638-7","url":null,"abstract":"<p><strong>Background: </strong>Identifying whether there is residual carcinoma in remaining suspicious calcifications after neoadjuvant chemotherapy (NAC) in breast cancer patients can provide crucial information for surgeons in determining the most appropriate surgical approach. Therefore, we investigated factors predicting calcifications without residual carcinoma (ypCalc_0) or with residual carcinoma (ypCalc_ca) and aimed to develop a prediction model for patients exhibiting residual suspicious calcifications on mammography but complete response on MRI after NAC.</p><p><strong>Methods: </strong>This retrospective study included breast cancer patients undergoing NAC, showing residual suspicious mammographic calcifications but complete response on MRI between January 2019 and December 2020 (development set) and between January 2021 and December 2022 (validation set). Multivariable logistic regression analysis identified significant factors associated with ypCalc_0. The prediction model, developed using a decision tree and factors from logistic regression analysis, was validated in the validation set.</p><p><strong>Results: </strong>The development set included 134 women (mean age, 50.6 years; 91 with ypCalc_0 and 43 with ypCalc_ca) and validation set included 146 women (mean age, 51.0 years; 108 with ypCalc_0 and 38 with ypCalc_ca). Molecular subtype (P = .0002) and high Ki-67 (P = .02) emerged as significant independent factors associated with ypCalc_0 in the development set. The prediction model, incorporating hormone receptor (HR)-/human epidermal growth factor receptor 2 (HER2)+ with high Ki-67 as ypCalc_0 predictors, and HR+/HER2- cancers or HR+/HER2+ or triple-negative (TN) cancers with low Ki-67, as ypCalc_ca predictors, achieved an area under receiver operating characteristic curve of 0.844 (95% CI 0.774-0.914) in the validation set.</p><p><strong>Conclusion: </strong>Minimized surgery may be considered for managing residual calcifications in HR-/HER2+ with high Ki-67 cancers, while complete excision is recommended for HR+/HER2- breast cancers or for HR+/HER2+or TN breast cancers with low Ki-67.</p>","PeriodicalId":56083,"journal":{"name":"Breast Cancer","volume":" ","pages":"109-119"},"PeriodicalIF":4.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142333136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
A genome-wide CRISPR/Cas9 knockout screen identifies SEMA3F gene for resistance to cyclin-dependent kinase 4 and 6 inhibitors in breast cancer. 全基因组 CRISPR/Cas9 基因敲除筛选确定了 SEMA3F 基因对乳腺癌细胞周期蛋白依赖性激酶 4 和 6 抑制剂的耐药性。
IF 4 3区 医学 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2025-01-01 Epub Date: 2024-10-01 DOI: 10.1007/s12282-024-01641-y
Yuko Kawai, Aiko Nagayama, Kazuhiro Miyao, Makoto Takeuchi, Takamichi Yokoe, Tomoe Kameyama, Xinyue Wang, Tomoko Seki, Maiko Takahashi, Tetsu Hayashida, Yuko Kitagawa

Background: Palbociclib is a cell-cycle targeted small molecule agent used as one of the standards of care in combination with endocrine therapy for patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer. Although several gene alterations such as loss of Rb gene and amplification of p16 gene are known to be conventional resistance mechanisms to cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors, the comprehensive landscape of resistance is not yet fully elucidated. The purpose of this study is to identify the novel resistant genes to the CDK4/6 inhibitors in HR-positive HER2-negative breast cancer.

Methods: The whole genome knockout screen using CRISPR/Cas9 genome editing was conducted in MCF7 to identify resistant genes to palbociclib. The candidate genes for resistance were selected by NGS analysis and GSEA analysis and validated by cell viability assay and mouse xenograft models.

Results: We identified eight genes including RET, TIRAP, GNRH1, SEMA3F, SEMA5A, GATA4, NOD1, SSTR1 as candidate genes from the whole genome knockout screen. Among those, knockdown of SEMA3F by siRNA significantly and consistently increased the cell viability in the presence of CDK4/6 inhibitors in vitro and in vivo. Furthermore, the level of p-Rb was maintained in the palbociclib treated SEMA3F-downregulated cells, indicating that the resistance is driven by increased activity of cyclin kinases.

Conclusion: Our observation provided the first evidence of SEMA3F as a regulator of sensitivity to CDK4/6 inhibitors in breast cancer. The detailed mechanisms of resistance deserve further functional studies to develop the better strategy to overcome resistance in CDK4/6 inhibitors.

背景介绍帕博西尼(Palbociclib)是一种细胞周期靶向小分子药物,是激素受体(HR)阳性、人表皮生长因子受体2(HER2)阴性晚期乳腺癌患者联合内分泌治疗的标准疗法之一。尽管已知Rb基因缺失和p16基因扩增等几种基因改变是细胞周期蛋白依赖性激酶4和6(CDK4/6)抑制剂的常规耐药机制,但耐药的全面情况尚未完全阐明。本研究的目的是鉴定HR阳性HER2阴性乳腺癌患者对CDK4/6抑制剂的新型耐药基因:方法:利用CRISPR/Cas9基因组编辑技术对MCF7进行全基因组敲除筛选,以确定对palbociclib的耐药基因。方法:利用 CRISPR/Cas9 基因组编辑技术在 MCF7 中进行全基因组敲除筛选,找出对 palbociclib 耐药的候选基因,通过 NGS 分析和 GSEA 分析筛选出耐药的候选基因,并通过细胞活力测定和小鼠异种移植模型进行验证:结果:通过全基因组敲除筛选,我们确定了RET、TIRAP、GNRH1、SEMA3F、SEMA5A、GATA4、NOD1、SSTR1等8个基因为候选基因。其中,在体外和体内CDK4/6抑制剂存在的情况下,通过siRNA敲除SEMA3F能显著且持续地提高细胞活力。此外,p-Rb的水平在palbociclib处理的SEMA3F-downregulated细胞中得以维持,这表明耐药性是由细胞周期蛋白激酶活性增加驱动的:我们的观察首次证明了SEMA3F是乳腺癌CDK4/6抑制剂敏感性的调节因子。耐药性的详细机制值得进一步的功能性研究,以制定更好的策略来克服 CDK4/6 抑制剂的耐药性。
{"title":"A genome-wide CRISPR/Cas9 knockout screen identifies SEMA3F gene for resistance to cyclin-dependent kinase 4 and 6 inhibitors in breast cancer.","authors":"Yuko Kawai, Aiko Nagayama, Kazuhiro Miyao, Makoto Takeuchi, Takamichi Yokoe, Tomoe Kameyama, Xinyue Wang, Tomoko Seki, Maiko Takahashi, Tetsu Hayashida, Yuko Kitagawa","doi":"10.1007/s12282-024-01641-y","DOIUrl":"10.1007/s12282-024-01641-y","url":null,"abstract":"<p><strong>Background: </strong>Palbociclib is a cell-cycle targeted small molecule agent used as one of the standards of care in combination with endocrine therapy for patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer. Although several gene alterations such as loss of Rb gene and amplification of p16 gene are known to be conventional resistance mechanisms to cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors, the comprehensive landscape of resistance is not yet fully elucidated. The purpose of this study is to identify the novel resistant genes to the CDK4/6 inhibitors in HR-positive HER2-negative breast cancer.</p><p><strong>Methods: </strong>The whole genome knockout screen using CRISPR/Cas9 genome editing was conducted in MCF7 to identify resistant genes to palbociclib. The candidate genes for resistance were selected by NGS analysis and GSEA analysis and validated by cell viability assay and mouse xenograft models.</p><p><strong>Results: </strong>We identified eight genes including RET, TIRAP, GNRH1, SEMA3F, SEMA5A, GATA4, NOD1, SSTR1 as candidate genes from the whole genome knockout screen. Among those, knockdown of SEMA3F by siRNA significantly and consistently increased the cell viability in the presence of CDK4/6 inhibitors in vitro and in vivo. Furthermore, the level of p-Rb was maintained in the palbociclib treated SEMA3F-downregulated cells, indicating that the resistance is driven by increased activity of cyclin kinases.</p><p><strong>Conclusion: </strong>Our observation provided the first evidence of SEMA3F as a regulator of sensitivity to CDK4/6 inhibitors in breast cancer. The detailed mechanisms of resistance deserve further functional studies to develop the better strategy to overcome resistance in CDK4/6 inhibitors.</p>","PeriodicalId":56083,"journal":{"name":"Breast Cancer","volume":" ","pages":"120-131"},"PeriodicalIF":4.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142333131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
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Breast Cancer
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