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Reliability of Magseed® marking before neoadjuvant systemic therapy with subsequent contrast-enhanced mammography in patients with non-palpable breast cancer lesions after treatment: the MAGMA study. 新辅助系统治疗前的 Magseed® 标记与随后的对比增强乳腺 X 线造影术对治疗后无法触及乳腺癌病灶患者的可靠性:MAGMA 研究。
IF 3 3区 医学 Q2 ONCOLOGY Pub Date : 2024-11-01 Epub Date: 2024-06-20 DOI: 10.1007/s10549-024-07407-6
Eva Iglesias Bravo, Antonio Mariscal Martínez, Helena Peris Alvà, Diego Riol Sancho, José Carlos Antela López, Joel Aranda Sánchez, Pilar Escobar Casa, Cristina Gómez de Las Heras, María Antonia Fernández Venegas, Eduarda García Vidal, Elisabeth Delgado Begines, Carmen García Mur, Isabel Vicente, Carmen Casamayor, Silvia Cruz, Anabel García Barrado

Purpose: To assess the reliability of excising residual breast cancer lesions after neoadjuvant systemic therapy (NAST) using a previously localized paramagnetic seed (Magseed®) and the subsequent use of contrast-enhanced spectral mammography (CESM) to evaluate response.

Methods: Observational, prospective, multicenter study including adult women (> 18 years) with invasive breast carcinoma undergoing NAST between January 2022 and February 2023 with non-palpable tumor lesions at surgery. Radiologists marked tumors with Magseed® during biopsy before NAST, and surgeons excised tumors guided by the Sentimag® magnetometer. CESMs were performed before and after NAST to evaluate tumor response (Response Evaluation Criteria for Solid Tumors [RECIST]). We considered intraoperative, surgical, and CESM-related variables and histological response.

Results: We analyzed 109 patients (median [IQR] age of 55.0 [46.0, 65.0] years). Magseed® was retrieved from breast tumors in all surgeries (100%; 95% CI 95.47-100.0%) with no displacement and was identified by radiology in 106 patients (97.24%), a median (IQR) of 176.5 (150.0, 216.3) days after marking. Most surgeries (94.49%) were conservative; they lasted a median (IQR) of 22.5 (14.75, 40.0) min (95% CI 23.59-30.11 min). Most dissected tumor margins (93.57%) were negative, and few patients (5.51%) needed reintervention. Magseed® was identified using CESM in all patients (100%); RECIST responses correlated with histopathological evaluations of dissected tumors using the Miller-Payne response grade (p < 0.0001) and residual lesion diameter (p < 0.0001). Also 69 patients (63.3%) answered a patient's satisfaction survey and 98.8% of them felt very satisfied with the entire procedure.

Conclusion: Long-term marking of breast cancer lesions with Magseed® is a reliable and feasible method in patients undergoing NAST and may be used with subsequent CESM.

目的:评估使用先前定位的顺磁种子(Magseed®)进行新辅助系统治疗(NAST)后切除残留乳腺癌病灶的可靠性,以及随后使用对比增强光谱乳腺放射摄影术(CESM)评估反应的可靠性:观察性、前瞻性、多中心研究,包括2022年1月至2023年2月期间接受NAST治疗的浸润性乳腺癌成年女性(大于18岁),手术时肿瘤病灶不可触及。放射科医生在NAST前的活检中用Magseed®标记肿瘤,外科医生在Sentimag®磁力计的引导下切除肿瘤。在 NAST 前后进行 CESM,以评估肿瘤反应(实体瘤反应评估标准 [RECIST])。我们考虑了术中、手术和 CESM 相关变量以及组织学反应:我们分析了 109 名患者(中位数[IQR]年龄为 55.0 [46.0, 65.0]岁)。在所有手术中(100%;95% CI 95.47-100.0%),Magseed®都能从乳腺肿瘤中取出,且没有移位,106 例患者(97.24%)在标记后中位数(IQR)176.5(150.0,216.3)天通过放射学鉴定。大多数手术(94.49%)是保守性的;手术时间中位数(IQR)为 22.5(14.75, 40.0)分钟(95% CI 23.59-30.11 分钟)。大部分切除的肿瘤边缘(93.57%)是阴性的,只有极少数患者(5.51%)需要重新介入。所有患者(100%)都使用 CESM 对 Magseed® 进行了识别;RECIST 反应与使用 Miller-Payne 反应分级对切除肿瘤进行的组织病理学评估相关(P 结论:Magseed® 是一种可用于乳腺癌病灶标记的长期标记方法:使用 Magseed® 对乳腺癌病灶进行长期标记是一种可靠可行的方法,适用于接受 NAST 的患者,并可与后续的 CESM 一起使用。
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引用次数: 0
Real-world use patterns, effectiveness, and tolerability of sacituzumab govitecan for second-line and later-line treatment of metastatic triple-negative breast cancer in the United States. 美国用于转移性三阴性乳腺癌二线和晚线治疗的sacituzumab govitecan的实际使用模式、有效性和耐受性。
IF 3 3区 医学 Q2 ONCOLOGY Pub Date : 2024-11-01 Epub Date: 2024-06-21 DOI: 10.1007/s10549-024-07412-9
Kevin Kalinsky, Laura Spring, Clinton Yam, Manali Ajay Bhave, Ioanna Ntalla, Catherine Lai, Nikoleta Sjekloca, Brian Stwalley, Michael Stokes, Aliki Taylor, Rita Nanda

Purpose: Patients with metastatic triple-negative breast cancer (mTNBC) have poor prognosis and limited treatment options. Sacituzumab govitecan (SG), a Trop-2-directed antibody-drug conjugate, is approved for patients with mTNBC who have received ≥ 2 systemic therapies (≥ 1 in the metastatic setting) based on the ASCENT study (NCT02574455). The current study describes real-world SG use and outcomes in patients with mTNBC in the United States.

Methods: This retrospective, observational study included adult patients with mTNBC from the ConcertAI Patient360™ database who received SG in the second line (2L) and later from April 2020 to May 2022. SG use patterns, effectiveness, and tolerability are described.

Results: This analysis included 230 patients (median age 60 years, 26% Black, 17% with ECOG performance status ≥ 2, 66% in community settings; median of 2 prior lines of treatment in the metastatic setting); median follow-up was 7.2 months. Median (95% CI) real-world overall survival was 10.0 (8.3-11.1) months for all patients and 13.9 (9.8-not estimable) months in the 2L subgroup (n = 77). Granulocyte-colony stimulating factor (G-CSF) was administered concomitantly with SG in 134 (58%) patients; 35 (15%) received G-CSF for the first time. Median (IQR) time from SG start to G-CSF use was 8.5 (8.0-29.0) days. Seventeen (7%) patients discontinued SG due to toxicity.

Conclusions: Using a real-world, ethnically diverse population of patients with mTNBC presenting with poor prognosis, these data reinforced the findings from ASCENT. In routine clinical practice, SG is an effective treatment in the 2L setting, consistent with treatment guidelines.

目的:转移性三阴性乳腺癌(mTNBC)患者预后较差,治疗选择有限。根据ASCENT研究(NCT02574455),萨妥珠单抗-戈维替康(SG)是一种Trop-2导向的抗体-药物共轭物,已被批准用于接受过≥2次全身治疗(转移性治疗≥1次)的mTNBC患者。本研究描述了美国 mTNBC 患者使用 SG 的实际情况和结果:这项回顾性观察研究纳入了 ConcertAI Patient360™ 数据库中 2020 年 4 月至 2022 年 5 月期间在二线(2L)及以后接受 SG 治疗的 mTNBC 成年患者。结果:本次分析共纳入 230 名患者(中位年龄 60 岁,26% 为黑人,17% ECOG 表 现状态≥ 2,66% 在社区环境中;中位在转移性环境中接受过 2 线治疗);中位随访时间为 7.2 个月。所有患者的实际总生存期中位数(95% CI)为10.0(8.3-11.1)个月,2L亚组(n = 77)为13.9(9.8-无法估计)个月。134例(58%)患者在使用SG的同时使用了粒细胞集落刺激因子(G-CSF);35例(15%)患者首次使用G-CSF。从开始使用 SG 到使用 G-CSF 的中位(IQR)时间为 8.5(8.0-29.0)天。17名(7%)患者因毒性而停用SG:这些数据利用真实世界中不同种族的预后不良的 mTNBC 患者,加强了 ASCENT 的研究结果。在常规临床实践中,SG 是一种有效的 2L 治疗方法,符合治疗指南的要求。
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引用次数: 0
Concordant and discordant breast density patterns by different approaches for assessing breast density and breast cancer risk. 采用不同方法评估乳腺密度和乳腺癌风险时的一致和不一致乳腺密度模式。
IF 3 3区 医学 Q2 ONCOLOGY Pub Date : 2024-11-01 DOI: 10.1007/s10549-024-07541-1
Yoosun Cho, Eun Kyung Park, Yoosoo Chang, Mi-Ri Kwon, Eun Young Kim, Minjeong Kim, Boyoung Park, Sanghyup Lee, Han Eol Jeong, Ki Hwan Kim, Tae Soo Kim, Hyeonsoo Lee, Ria Kwon, Ga-Young Lim, JunHyeok Choi, Shin Ho Kook, Seungho Ryu

Purpose: To examine the discrepancy in breast density assessments by radiologists, LIBRA software, and AI algorithm and their association with breast cancer risk.

Methods: Among 74,610 Korean women aged ≥ 34 years, who underwent screening mammography, density estimates obtained from both LIBRA and the AI algorithm were compared to radiologists using BI-RADS density categories (A-D, designating C and D as dense breasts). The breast cancer risks were compared according to concordant or discordant dense breasts identified by radiologists, LIBRA, and AI. Cox-proportional hazards models were used to determine adjusted hazard ratios (aHRs) [95% confidence intervals (CIs)].

Results: During a median follow-up of 9.9 years, 479 breast cancer cases developed. Compared to the reference non-dense breast group, the aHRs (95% CIs) for breast cancer were 2.37 (1.68-3.36) for radiologist-classified dense breasts, 1.30 (1.05-1.62) for LIBRA, and 2.55 (1.84-3.56) for AI. For different combinations of breast density assessment, aHRs (95% CI) for breast cancer were 2.40 (1.69-3.41) for radiologist-dense/LIBRA-non-dense, 11.99 (1.64-87.62) for radiologist-non-dense/LIBRA-dense, and 2.99 (1.99-4.50) for both dense breasts, compared to concordant non-dense breasts. Similar trends were observed with radiologists/AI classification: the aHRs (95% CI) were 1.79 (1.02-3.12) for radiologist-dense/AI-non-dense, 2.43 (1.24-4.78) for radiologist-non-dense/AI-dense, and 3.23 (2.15-4.86) for both dense breasts.

Conclusion: The risk of breast cancer was highest in concordant dense breasts. Discordant dense breast cases also had a significantly higher risk of breast cancer, especially when identified as dense by either AI or LIBRA, but not radiologists, compared to concordant non-dense breast cases.

目的:研究放射科医生、LIBRA软件和人工智能算法对乳腺密度评估的差异及其与乳腺癌风险的关系:在 74,610 名年龄≥ 34 岁、接受过乳腺 X 光筛查的韩国女性中,将 LIBRA 和 AI 算法得出的密度估算值与放射科医生使用 BI-RADS 密度分类(A-D,将 C 和 D 指定为致密乳房)得出的密度估算值进行比较。根据放射科医生、LIBRA 和 AI 确定的一致或不一致致密乳房对乳腺癌风险进行了比较。采用Cox比例危险模型确定调整后的危险比(aHRs)[95%置信区间(CIs)]:中位随访 9.9 年,共发现 479 例乳腺癌病例。与参考的非致密乳房组相比,放射医师分类致密乳房的乳腺癌aHRs(95% 置信区间)为2.37(1.68-3.36),LIBRA为1.30(1.05-1.62),AI为2.55(1.84-3.56)。对于不同的乳房密度评估组合,与一致的非致密乳房相比,放射科医生致密/LIBRA-非致密乳房的乳腺癌aHRs(95% CI)为2.40(1.69-3.41),放射科医生-非致密/LIBRA-致密乳房的aHRs为11.99(1.64-87.62),两种致密乳房的aHRs均为2.99(1.99-4.50)。放射科医生/AI分类也观察到类似的趋势:放射科医生-致密/AI-非致密的aHRs(95% CI)为1.79(1.02-3.12),放射科医生-非致密/AI-致密的aHRs(95% CI)为2.43(1.24-4.78),两个致密乳房的aHRs(95% CI)为3.23(2.15-4.86):结论:一致致密乳房罹患乳腺癌的风险最高。与不一致的非致密乳房病例相比,不一致的致密乳房病例患乳腺癌的风险也明显较高,尤其是被 AI 或 LIBRA(而非放射科医生)确定为致密的病例。
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引用次数: 0
The differences between pure and mixed invasive micropapillary breast cancer: the epithelial-mesenchymal transition molecules and prognosis. 纯性和混合性浸润性微乳头状瘤的差异:上皮-间质转化分子和预后。
IF 3 3区 医学 Q2 ONCOLOGY Pub Date : 2024-11-01 Epub Date: 2024-07-02 DOI: 10.1007/s10549-024-07384-w
Ozden Oz, Resmiye Irmak Yuzuguldu, Ayse Yazici, Demet Kocatepe Cavdar, Cengiz Yilmaz, Mucteba Ozturk, Hilal Duzel, Duygu Gurel

Purpose: Invasive micropapillary carcinoma (IMPC) of the breast is known for its high metastatic potential, but the definition of pure and mixed IMPC remains unclear. This retrospective cohort study aims to investigate the prognostic significance of the micropapillary component ratio and the expression of critical molecules of epithelial-mesenchymal transition (EMT), including E-cadherin (E-cad), N-cadherin (N-cad), CD44s, and β-catenin (β-cat), in distinguishing between pure and mixed IMPCs.

Methods: We analyzed 100 cases of locally advanced IMPC between 2000 and 2018 and excluded patients who received neoadjuvant chemotherapy. Pure IMPC was defined as having a micropapillary component of over 90%. A comprehensive recording of prognostic parameters was conducted. The IMPC areas were analyzed using the immunohistochemical (IHC) staining method on the microarray set for pure and mixed IMPC patients. Pearson's chi-square, Fisher's exact tests, Kaplan-Meier analysis, and Cox proportional hazards analysis were employed.

Results: The comparative survival analysis of the entire group, based on overall survival (OS) and disease-free survival (DFS), revealed no significant difference between the pure and mixed groups (P = 0.480, HR = 1.474 [0.502-4.325] and P = 0.390, HR = 1.587 [0.550-4.640], respectively). However, in the pure IMPC group, certain factors were found to be associated with a higher risk of short survival. These factors included skin involvement (P = 0.050), pT3&4 category (P = 0.006), a ratio of intraductal component (> 5%) (P = 0.032), and high-level expression of N-cad (P = 0.020). Notably, none of the risk factors identified for short OS in pure IMPC cases were observed as significant risks in mixed cases and vice versa. Furthermore, N-cad was identified as a poor prognostic marker for OS in pure IMPCs (P = 0.002).

Conclusion: The selection of a 90% ratio for classifying pure IMPCs revealed significant differences in certain molecular and prognostic parameters between pure and mixed groups. Notably, the involvement of N-cadherin in the epithelial-mesenchymal transition (EMT) process provided crucial insights for predicting OS and DFS while also distinguishing between the two groups. These findings strongly support the notion that the pure IMPC subgroup represents a distinct entity characterized by unique molecular characteristics and behavioral patterns.

目的:众所周知,乳腺浸润性微乳头状癌(IMPC)具有很高的转移潜力,但纯合性和混合性IMPC的定义仍不明确。这项回顾性队列研究旨在探讨微乳头成分比例和上皮-间质转化(EMT)关键分子(包括E-cadherin(E-cad)、N-cadherin(N-cad)、CD44s和β-catenin(β-cat))的表达对区分纯合型和混合型IMPC的预后意义:我们分析了2000年至2018年间的100例局部晚期IMPC,并排除了接受新辅助化疗的患者。纯IMPC定义为微乳头成分超过90%。对预后参数进行了全面记录。采用免疫组化(IHC)染色法对纯合IMPC和混合IMPC患者的微阵列集进行IMPC区域分析。采用了皮尔逊卡方检验、费雪精确检验、Kaplan-Meier分析和Cox比例危险度分析:结果:基于总生存期(OS)和无病生存期(DFS)的全组生存期比较分析显示,纯合组和混合组之间无显著差异(分别为 P = 0.480,HR = 1.474 [0.502-4.325] 和 P = 0.390,HR = 1.587 [0.550-4.640])。然而,在纯 IMPC 组中,发现某些因素与较高的短期存活风险相关。这些因素包括皮肤受累(P = 0.050)、pT3&4 类(P = 0.006)、导管内成分比例(> 5%)(P = 0.032)和 N-cad 的高水平表达(P = 0.020)。值得注意的是,在纯IMPC病例中发现的导致短OS的风险因素在混合病例中均无明显风险,反之亦然。此外,N-cad被确定为纯IMPC患者OS的不良预后标志物(P = 0.002):结论:选择 90% 的比例对纯 IMPCs 进行分类,发现纯 IMPCs 和混合组之间在某些分子和预后参数上存在显著差异。值得注意的是,N-cadherin参与上皮-间质转化(EMT)过程为预测OS和DFS提供了重要依据,同时也区分了两组患者。这些发现有力地支持了这样一种观点,即纯合子 IMPC 亚组代表了一个不同的实体,具有独特的分子特征和行为模式。
{"title":"The differences between pure and mixed invasive micropapillary breast cancer: the epithelial-mesenchymal transition molecules and prognosis.","authors":"Ozden Oz, Resmiye Irmak Yuzuguldu, Ayse Yazici, Demet Kocatepe Cavdar, Cengiz Yilmaz, Mucteba Ozturk, Hilal Duzel, Duygu Gurel","doi":"10.1007/s10549-024-07384-w","DOIUrl":"10.1007/s10549-024-07384-w","url":null,"abstract":"<p><strong>Purpose: </strong>Invasive micropapillary carcinoma (IMPC) of the breast is known for its high metastatic potential, but the definition of pure and mixed IMPC remains unclear. This retrospective cohort study aims to investigate the prognostic significance of the micropapillary component ratio and the expression of critical molecules of epithelial-mesenchymal transition (EMT), including E-cadherin (E-cad), N-cadherin (N-cad), CD44s, and β-catenin (β-cat), in distinguishing between pure and mixed IMPCs.</p><p><strong>Methods: </strong>We analyzed 100 cases of locally advanced IMPC between 2000 and 2018 and excluded patients who received neoadjuvant chemotherapy. Pure IMPC was defined as having a micropapillary component of over 90%. A comprehensive recording of prognostic parameters was conducted. The IMPC areas were analyzed using the immunohistochemical (IHC) staining method on the microarray set for pure and mixed IMPC patients. Pearson's chi-square, Fisher's exact tests, Kaplan-Meier analysis, and Cox proportional hazards analysis were employed.</p><p><strong>Results: </strong>The comparative survival analysis of the entire group, based on overall survival (OS) and disease-free survival (DFS), revealed no significant difference between the pure and mixed groups (P = 0.480, HR = 1.474 [0.502-4.325] and P = 0.390, HR = 1.587 [0.550-4.640], respectively). However, in the pure IMPC group, certain factors were found to be associated with a higher risk of short survival. These factors included skin involvement (P = 0.050), pT3&4 category (P = 0.006), a ratio of intraductal component (> 5%) (P = 0.032), and high-level expression of N-cad (P = 0.020). Notably, none of the risk factors identified for short OS in pure IMPC cases were observed as significant risks in mixed cases and vice versa. Furthermore, N-cad was identified as a poor prognostic marker for OS in pure IMPCs (P = 0.002).</p><p><strong>Conclusion: </strong>The selection of a 90% ratio for classifying pure IMPCs revealed significant differences in certain molecular and prognostic parameters between pure and mixed groups. Notably, the involvement of N-cadherin in the epithelial-mesenchymal transition (EMT) process provided crucial insights for predicting OS and DFS while also distinguishing between the two groups. These findings strongly support the notion that the pure IMPC subgroup represents a distinct entity characterized by unique molecular characteristics and behavioral patterns.</p>","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11452530/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141490908","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Letter to the BRCT editor. 致 BRCT 编辑的信。
IF 3 3区 医学 Q2 ONCOLOGY Pub Date : 2024-11-01 Epub Date: 2024-08-10 DOI: 10.1007/s10549-024-07445-0
Pierre Bourgeois
{"title":"Letter to the BRCT editor.","authors":"Pierre Bourgeois","doi":"10.1007/s10549-024-07445-0","DOIUrl":"10.1007/s10549-024-07445-0","url":null,"abstract":"","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141911690","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 novel role of IGFBP5 in the migration, invasion and spheroids formation induced by IGF-I and insulin in MCF-7 breast cancer cells. IGFBP5在IGF-I和胰岛素诱导的MCF-7乳腺癌细胞迁移、侵袭和球体形成中的新作用。
IF 3 3区 医学 Q2 ONCOLOGY Pub Date : 2024-11-01 Epub Date: 2024-06-19 DOI: 10.1007/s10549-024-07397-5
Karem Rodríguez-Rojas, Pedro Cortes-Reynosa, Pablo Torres-Alamilla, Nínive Rodríguez-Ochoa, Eduardo Perez Salazar

Purpose: The insulin-like growth factor (IGF) system includes IGF-I, IGF-II insulin and their membrane receptors. IGF system also includes a family of proteins namely insulin-like growth factor-binding proteins (IGFBPs) composed for six major members (IGFBP-1 to IGFBP6), which capture, transport and prolonging half-life of IGFs. However, it has been described that IGFBPs can also have other functions.

Methods: IGFBP5 expression was inhibited by shRNAs, migration was analyzed by scratch-wound assays, invasion assays were performed by the Boyden chamber method, spheroids formation assays were performed on ultra-low attachment surfaces, expression and phosphorylation of proteins were analyzed by Western blot.

Results: IGFBP5 is a repressor of IGF-IR expression, but it is not a repressor of IR in MCF-7 breast cancer cells. In addition, IGFBP5 is a suppressor of migration and MMP-9 secretion induced by IGF-I and insulin, but it does not regulate invasion in MCF-7 cells. IGFBP5 also is a repressor of MCF-7 spheroids formation. However treatment with 340 nM rescues the inhibitory effect of IGFBP in the MCF-7 spheroids formation.

Conclusion: IGFBP5 regulates IGF-IR expression, migration and MMP-9 secretion induced by IGF-I and/or insulin, and the spheroids formation in MCF-7 breast cancer cells.

目的:胰岛素样生长因子(IGF)系统包括 IGF-I、IGF-II 胰岛素及其膜受体。胰岛素样生长因子系统还包括一个蛋白质家族,即胰岛素样生长因子结合蛋白(IGFBPs),由六个主要成员(IGFBP-1 至 IGFBP6)组成,可捕获、转运和延长胰岛素样生长因子的半衰期。然而,有研究表明 IGFBPs 还具有其他功能:方法:用 shRNAs 抑制 IGFBP5 的表达,用划痕法分析迁移,用 Boyden 室法进行侵袭试验,在超低附着面上进行球体形成试验,用 Western 印迹法分析蛋白质的表达和磷酸化:结果:IGFBP5是IGF-IR表达的抑制因子,但在MCF-7乳腺癌细胞中不是IR的抑制因子。此外,IGFBP5 还是 IGF-I 和胰岛素诱导的迁移和 MMP-9 分泌的抑制因子,但它并不调控 MCF-7 细胞的侵袭。IGFBP5 还是 MCF-7 球形细胞形成的抑制因子。然而,用 340 nM 处理可挽救 IGFBP 对 MCF-7 球形细胞形成的抑制作用:结论:IGFBP5调节IGF-IR的表达、IGF-I和/或胰岛素诱导的迁移和MMP-9的分泌,以及MCF-7乳腺癌细胞球形体的形成。
{"title":"A novel role of IGFBP5 in the migration, invasion and spheroids formation induced by IGF-I and insulin in MCF-7 breast cancer cells.","authors":"Karem Rodríguez-Rojas, Pedro Cortes-Reynosa, Pablo Torres-Alamilla, Nínive Rodríguez-Ochoa, Eduardo Perez Salazar","doi":"10.1007/s10549-024-07397-5","DOIUrl":"10.1007/s10549-024-07397-5","url":null,"abstract":"<p><strong>Purpose: </strong>The insulin-like growth factor (IGF) system includes IGF-I, IGF-II insulin and their membrane receptors. IGF system also includes a family of proteins namely insulin-like growth factor-binding proteins (IGFBPs) composed for six major members (IGFBP-1 to IGFBP6), which capture, transport and prolonging half-life of IGFs. However, it has been described that IGFBPs can also have other functions.</p><p><strong>Methods: </strong>IGFBP5 expression was inhibited by shRNAs, migration was analyzed by scratch-wound assays, invasion assays were performed by the Boyden chamber method, spheroids formation assays were performed on ultra-low attachment surfaces, expression and phosphorylation of proteins were analyzed by Western blot.</p><p><strong>Results: </strong>IGFBP5 is a repressor of IGF-IR expression, but it is not a repressor of IR in MCF-7 breast cancer cells. In addition, IGFBP5 is a suppressor of migration and MMP-9 secretion induced by IGF-I and insulin, but it does not regulate invasion in MCF-7 cells. IGFBP5 also is a repressor of MCF-7 spheroids formation. However treatment with 340 nM rescues the inhibitory effect of IGFBP in the MCF-7 spheroids formation.</p><p><strong>Conclusion: </strong>IGFBP5 regulates IGF-IR expression, migration and MMP-9 secretion induced by IGF-I and/or insulin, and the spheroids formation in MCF-7 breast cancer cells.</p>","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11452427/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141417763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Information needs persist after genetic counseling and testing for BRCA1/2 and Lynch Syndrome. BRCA1/2 和林奇综合征遗传咨询和检测后,信息需求依然存在。
IF 3 3区 医学 Q2 ONCOLOGY Pub Date : 2024-11-01 Epub Date: 2024-07-24 DOI: 10.1007/s10549-024-07377-9
Lucy A Peipins, Sabitha Dasari, Melissa Heim Viox, Juan L Rodriguez

Purpose: Research has shown that cancer genetic risk is often not well understood by patients undergoing genetic testing and counseling. We describe the barriers to understanding genetic risk and the needs of high-risk persons and cancer survivors who have undergone genetic testing.

Methods: Using data from an internet survey of adults living in the USA who responded 'yes' to having ever had a genetic test to determine cancer risk (N = 696), we conducted bivariate analyses and multivariable logistic regression models to evaluate associations between demographic, clinical, and communication-related variables by our key outcome of having vs. not having enough information about genetics and cancer to speak with family. Percentages for yes and no responses to queries about unmet informational needs were calculated. Patient satisfaction with counseling and percentage disclosure of genetic risk status to family were also calculated.

Results: We found that a lack of resources provided by provider to inform family members and a lack of materials provided along with genetic test results were strongly associated with not having enough information about genetics and cancer (OR 4.54 95% CI 2.40-8.59 and OR 2.19 95% CI 1.16-4.14 respectively). Among participants undergoing genetic counseling, almost half reported needing more information on what genetic risk means for them and their family and how genetic testing results might impact future screening.

Conclusion: High levels of satisfaction with genetic counseling may not give a full picture of the patient-provider interaction and may miss potential unmet needs of the patient. Accessible resources and ongoing opportunities for updating family history information could reinforce knowledge about genetic risk.

目的:研究表明,接受基因检测和咨询的患者往往不太了解癌症遗传风险。我们描述了了解遗传风险的障碍,以及接受过基因检测的高危人群和癌症幸存者的需求:我们利用对美国成年人的互联网调查数据,这些成年人都回答 "是",他们曾经接受过基因检测以确定癌症风险(N = 696)。我们使用这些数据进行了双变量分析和多变量逻辑回归模型,以评估人口统计学、临床和沟通相关变量与我们的关键结果之间的关联,我们的关键结果是是否有足够的遗传学和癌症信息与家人交流。我们计算了患者对未满足的信息需求的回答 "是 "和 "否 "的百分比。此外,还计算了患者对咨询的满意度以及向家人透露遗传风险状况的百分比:结果:我们发现,医疗服务提供者缺乏向家庭成员提供信息的资源,以及缺乏与基因检测结果一起提供的资料,与未获得足够的遗传学和癌症信息密切相关(OR 4.54 95% CI 2.40-8.59 和 OR 2.19 95% CI 1.16-4.14)。在接受遗传咨询的参与者中,近半数人表示需要更多信息,以了解遗传风险对他们及其家庭的意义,以及遗传检测结果可能对未来筛查的影响:对遗传咨询的高满意度可能无法全面反映患者与提供者之间的互动,也可能会忽略患者潜在的未满足需求。可获取的资源和不断更新家族史信息的机会可以加强对遗传风险的了解。
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引用次数: 0
Association between homologous recombination deficiency status and carboplatin treatment response in early triple-negative breast cancer. 早期三阴性乳腺癌中同源重组缺陷状态与卡铂治疗反应之间的关系
IF 3 3区 医学 Q2 ONCOLOGY Pub Date : 2024-11-01 Epub Date: 2024-07-24 DOI: 10.1007/s10549-024-07436-1
Zheng Wang, Yujie Lu, Mengyuan Han, Anqi Li, Miao Ruan, Yiwei Tong, Cuiyan Yang, Xiaotian Zhang, Changbin Zhu, Chaofu Wang, Kunwei Shen, Lei Dong, Xiaosong Chen

Background: The aim of this study was to assess homologous recombination deficiency (HRD) status and its correlation with carboplatin treatment response in early triple-negative breast cancer (TNBC) patients.

Methods: Tumor tissues from 225 consecutive TNBC patients were evaluated with an HRD panel and homologous recombination-related (HRR) gene expression data. HRD positivity was defined as a high HRD score and/or BRCA1/2 pathogenic or likely pathogenic mutation. Clinicopathological factors, neoadjuvant treatment response, and prognosis were analyzed with respect to HRD status in these TNBC patients.

Results: HRD positivity was found in 53.3% of patients and was significantly related to high Ki67 levels (P = 0.001). In patients who received neoadjuvant chemotherapy, HRD positivity (P = 0.005) or a high HRD score (P = 0.003) was significantly associated with a greater pathological complete response (pCR) rate, especially in those treated with carboplatin-containing neoadjuvant regimens (HRD positivity vs. negativity: 50.00% vs. 17.65%, P = 0.040). HRD positivity was associated with favorable distant metastasis-free survival (hazard ratio HR 0.49, 95% confidence interval CI 0.26-0.90, P = 0.022) and overall survival (HR 0.45, 95% CI 0.20-0.99, P = 0.049), irrespective of carboplatin treatment.

Conclusion: TNBC patients with high HRDs had high Ki67 levels and BRCA mutations. HRD-positive TNBC patients treated with carboplatin had a higher pCR rate. Patients with HRD positivity had a better prognosis, irrespective of carboplatin treatment, warranting further evaluation.

背景:本研究旨在评估早期三阴性乳腺癌(TNBC)患者同源重组缺陷(HRD)状态及其与卡铂治疗反应的相关性:本研究旨在评估早期三阴性乳腺癌(TNBC)患者的同源重组缺陷(HRD)状态及其与卡铂治疗反应的相关性:用HRD面板和同源重组相关(HRR)基因表达数据评估了225例连续TNBC患者的肿瘤组织。HRD阳性定义为高HRD评分和/或BRCA1/2致病或可能致病突变。对这些TNBC患者的临床病理因素、新辅助治疗反应和预后与HRD状态的关系进行了分析:结果:53.3%的患者发现HRD阳性,且与高Ki67水平显著相关(P = 0.001)。在接受新辅助化疗的患者中,HRD阳性(P = 0.005)或高HRD评分(P = 0.003)与更高的病理完全反应(pCR)率显著相关,尤其是在接受含卡铂新辅助方案治疗的患者中(HRD阳性与阴性:50.00% vs. 17.65%,P = 0.040)。HRD阳性与良好的无远处转移生存率(危险比HR 0.49,95%置信区间CI 0.26-0.90,P = 0.022)和总生存率(HR 0.45,95%置信区间CI 0.20-0.99,P = 0.049)相关,与卡铂治疗无关:结论:高HRD的TNBC患者具有高Ki67水平和BRCA突变。接受卡铂治疗的HRD阳性TNBC患者的pCR率较高。无论卡铂治疗与否,HRD阳性患者的预后较好,值得进一步评估。
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引用次数: 0
Overcoming technical hurdles in mobile health: insights from the Fit2ThriveMB breast cancer study. 克服移动医疗的技术障碍:Fit2ThriveMB 乳腺癌研究的启示。
IF 3 3区 医学 Q2 ONCOLOGY Pub Date : 2024-11-01 Epub Date: 2024-09-05 DOI: 10.1007/s10549-024-07483-8
Qirui Guo, Mohan Liu, Yan Li, Qiang Sun
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引用次数: 0
Comparison of proportions and prognostic impact of pathological complete response between evaluations of representative specimen and total specimen in primary breast cancer after neoadjuvant chemoradiotherapy: an ancillary study of JCOG0306. 新辅助化放疗后原发性乳腺癌代表性标本和总标本病理完全反应比例及预后影响的比较:JCOG0306 的辅助研究。
IF 3 3区 医学 Q2 ONCOLOGY Pub Date : 2024-11-01 Epub Date: 2024-06-27 DOI: 10.1007/s10549-024-07408-5
Tadahiko Shien, Hitoshi Tsuda, Keita Sasaki, Junki Mizusawa, Futoshi Akiyama, Masafumi Kurosumi, Masataka Sawaki, Nobuko Tamura, Kiyo Tanaka, Takahiro Kogawa, Mina Takahashi, Naoki Hayashi, Hirofumi Mukai, Norikazu Masuda, Fumikata Hara, Hiroji Iwata

Background: In JCOG0306 trial, a phase II study to examine the efficacy of neoadjuvant chemotherapy followed by radiation therapy (NAC-RT) to primary breast cancer, pathological complete response (pCR) was evaluated from specimens of the representative cross-section including the tumor center that had been accurately marked [representative specimen (RS) method]. In this ancillary study, we examined if the RS method was comparable to the conventional total specimen (TS) method, which is widely employed in Japan, to identify the pCR group showing excellent prognosis.

Methods: We obtained long-term follow-up data of 103 patients enrolled in JCOG0306 trial. As histological therapeutic effect, pCR (ypT0 and ypT0/is) and quasi-pCR [QpCR, ypT0/is plus Grade 2b (only a few remaining invasive cancer cells)] were evaluated with RS and TS methods. Concordance of pCR between these two methods and associations of the pCR with prognosis were examined.

Results: ypT0, ypT0/is, and QpCR were observed in 28 (27.2%), 39 (37.9%), and 45 (43.7%) patients with RS method, whereas these were 20 (19.4%), 25 (24.3%) and 40 (38.9%) with TS method, respectively. Between RS and TS methods, concordance proportions of ypT0 and ypTis were 92.2% and 86.4%, respectively. Risk of recurrence of ypT0/is group was lower than that of non-ypT0/is group (HR 0.408, 95% CI [0.175-0.946], P = 0.037) and risk of death of ypT0/is group was lower than that of non-ypT0/is group (HR 0.251, 95% CI [0.073-0.857], P = 0.027). The ypT0 and ypT0/is groups with RS method showed excellent prognosis similarly with those with TS method, and RS method was able to differentiate the OS and RFS between pCR and non-pCR than TS method significantly even if pCR was classified ypT0 or ypT0/is. With TS method, QpCR criteria stratified patients into the better and worse prognosis groupsmore clearly than pCR criteria of ypT0 or ypT0/is.

Conclusions: RS method was comparable to TS method for the evaluation of pCR in the patients who received NAC-RT to primary breast cancer provided the tumor center was accurately marked. As pCR criteria with RS method, ypT0/is appeared more appropriate than ypT0.

研究背景JCOG0306试验是一项旨在研究新辅助化疗后放疗(NAC-RT)对原发性乳腺癌疗效的II期研究,在该试验中,病理完全反应(pCR)是通过包括肿瘤中心在内的准确标记的代表性横截面标本(代表性标本(RS)法)进行评估的。在这项辅助研究中,我们考察了 RS 法与日本广泛采用的传统的总标本法(TS)在确定预后良好的 pCR 组别方面是否具有可比性:方法:我们获得了参加 JCOG0306 试验的 103 例患者的长期随访数据。作为组织学治疗效果,我们用 RS 和 TS 方法评估了 pCR(ypT0 和 ypT0/is)和准 pCR [QpCR,ypT0/is 加 2b 级(仅存少量侵袭性癌细胞)]。结果:采用 RS 方法观察到 ypT0、ypT0/is 和 QpCR 的患者分别为 28 人(27.2%)、39 人(37.9%)和 45 人(43.7%),而采用 TS 方法则分别为 20 人(19.4%)、25 人(24.3%)和 40 人(38.9%)。在 RS 和 TS 方法中,ypT0 和 ypTis 的一致性比例分别为 92.2% 和 86.4%。ypT0/is 组的复发风险低于非 ypT0/is 组(HR 0.408,95% CI [0.175-0.946],P = 0.037),ypT0/is 组的死亡风险低于非 ypT0/is 组(HR 0.251,95% CI [0.073-0.857],P = 0.027)。采用RS方法的ypT0和ypT0/is组与采用TS方法的ypT0和ypT0/is组显示出相似的良好预后,即使pCR被归类为ypT0或ypT0/is,RS方法也能比TS方法显著区分pCR和非pCR的OS和RFS。在TS方法中,QpCR标准比pCR标准(ypT0或ypT0/is)更明确地将患者分为预后较好和预后较差的两组:结论:在对接受 NAC-RT 治疗的原发性乳腺癌患者进行 pCR 评估时,如果肿瘤中心标记准确,RS 法与 TS 法具有可比性。作为 RS 法的 pCR 标准,ypT0/is 似乎比 ypT0 更合适。
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引用次数: 0
期刊
Breast Cancer Research and Treatment
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