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Clinical significance of Notch receptors in triple negative breast cancer. Notch受体在三阴性乳腺癌中的临床意义。
Pub Date : 2022-02-04 DOI: 10.21203/rs.3.rs-1305178/v1
H. Shah, Mittal Mistry, Nupur Patel, H. Vora
BACKGROUNDThe Notch signaling pathway is an evolutionary conserved cell signaling pathway that plays an indispensable role in essential developmental processes. Aberrant activation of Notch pathway is known to initiate wide array of diseases and cancers.OBJECTIVETo evaluate the clinical significance of Notch receptors in Triple Negative Breast Cancer.METHODSWe evaluated the association between Notch receptors and clinicopathological parameters including disease-free survival and overall survival of one hundred TNBC patients by immunohistochemistry.RESULTSPositive expression of nuclear Notch1 receptor (18%) was found be significantly correlated with positive lymph node (p = 0.009), high BR score (p = 0.02) and necrosis (p = 0.004) while cytoplasmic expression of Notch2 receptor (26%) was significantly correlated with metastasis (p = 0.05), worse DFS (p = 0.05) and poor OS (p = 0.02) in TNBC patients. Membrane (18%) and cytonuclear (3%) Notch3 expression were significantly associated with poorly differentiated tumors (p = 0.007), high BR score (p = 0.002) and necrosis (p = 0.03) respectively. However, cytoplasmic Notch3 and Notch4 expression were negatively correlated with poor prognostic factors.CONCLUSIONSOur data indicated that Notch receptors play a key role in promoting TNBC and mainly, Notch2 may contribute to poor prognosis of the disease. Hence, it is implicated that Notch2 may serve as a potential biomarker and therapeutic target for TNBC.
Notch信号通路是一种进化保守的细胞信号通路,在重要的发育过程中起着不可或缺的作用。Notch通路的异常激活可引发多种疾病和癌症。目的探讨Notch受体在三阴性乳腺癌中的临床意义。方法采用免疫组化方法评价Notch受体与100例TNBC患者无病生存期和总生存期等临床病理参数的关系。结果核Notch1受体阳性表达(18%)与TNBC患者淋巴结阳性(p = 0.009)、高BR评分(p = 0.02)、坏死(p = 0.004)显著相关,细胞质Notch2受体阳性表达(26%)与TNBC患者转移(p = 0.05)、DFS加重(p = 0.05)、OS恶化(p = 0.02)显著相关。细胞膜(18%)和细胞核(3%)表达Notch3分别与低分化肿瘤(p = 0.007)、高BR评分(p = 0.002)和坏死(p = 0.03)显著相关。然而,细胞质Notch3和Notch4的表达与不良预后因素呈负相关。结论Notch受体在TNBC的发生中起关键作用,Notch2可能是导致TNBC预后不良的主要原因。因此,Notch2可能作为TNBC的潜在生物标志物和治疗靶点。
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引用次数: 0
Fibroadenoma of the breast; incidence of malignancy and indicators for surgical intervention: An analysis of 1392 patients. 乳腺纤维腺瘤;恶性肿瘤发生率及手术干预指标:1392例患者分析
Pub Date : 2022-01-01 DOI: 10.3233/BD-210074
Waleed Elnahas, Islam H Metwally, Khaled Bonna, Marco Youssef, Samar AbdAllah, Mohamed Bonna, Mohamed Ali Faried, Mohamed Atef Tira, Omar Hamdy

Background: Fibroadenomas are common among young females. The size of the lesion used to be an indication for further assessment or excision. With arising of the watch and see proponents, criteria for selecting patients are important to establish.

Methods: This is a retrospective study of a prospectively maintained database where all patients having the clinical/radiological provisional diagnosis of fibroadenoma and attending our center - from January 2008 to March 2020 - were enrolled. The primary outcome was the incidence of malignancy and the secondary outcomes were the correlation of malignancy-risk with epidemiologic and radiologic criteria.

Results: The study enrolled 1392 patients. The mean age of the patients was 35.7 + ∕- 13.1 years. The median of the longest diameter of the detected breast lesions was 25 mm. The incidence of malignancy was 188 (13.5%). The size of the lesion measured by largest diameter was insignificant (p = 0.99), while the patients' age, marital status, and imaging criteria as measured by BIRADS score were significant (<0.001).

Conclusion: Approaching patients with the age above 35 or with BIRADS 4 provisionally diagnosed with fibroadenomas should be cautious with biopsy and short-term follow-ups The size of the tumor alone should not be used as an indication for surgical intervention.

背景:纤维腺瘤常见于年轻女性。病变的大小曾经是进一步评估或切除的指示。随着“观察和观察”支持者的兴起,建立选择患者的标准变得非常重要。方法:这是一项前瞻性数据库的回顾性研究,其中纳入了2008年1月至2020年3月期间所有临床/放射学临时诊断为纤维腺瘤并在我们中心就诊的患者。主要结局是恶性肿瘤的发生率,次要结局是恶性肿瘤风险与流行病学和放射学标准的相关性。结果:该研究纳入了1392例患者。患者平均年龄为35.7±13.1岁。乳腺病灶最长直径中位数为25mm。恶性肿瘤188例(13.5%)。最大直径测量的病变大小差异无统计学意义(p = 0.99),而BIRADS评分测量的患者年龄、婚姻状况、影像学标准差异有统计学意义(结论:接近35岁以上或BIRADS 4暂时诊断为纤维腺瘤的患者应谨慎活检和短期随访,肿瘤大小不应单独作为手术干预的指征。
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引用次数: 2
Correlation between the expression of Ki67 and histopathological grade, tumor size, disease-free survival, and overall survival among breast cancer patients. 乳腺癌患者中Ki67表达与组织病理分级、肿瘤大小、无病生存期和总生存期的相关性
Pub Date : 2022-01-01 DOI: 10.3233/BD-229005
Radityo Budi Leksono, Rudy Thabry, Prihantono Prihantono, Fritz Nahusuly, Firdaus Kasim, William Hamdani, John Pieter, Indra Indra, Salman Ardi Syamsu, Muhammad Faruk

Introduction: Identifying Ki67, a monoclonal antibody that recognizes proliferating cells, is important for defining the level of proliferative activity among patients with breast cancer. The purpose of our study was to evaluate the correlation between Ki67's expression and histopathological grade, tumor size, disease-free survival (DFS), and overall survival (OS) among breast cancer patients.

Methods: Our retrospective cohort study involved examining 114 patients with breast cancer at our institution from January 2018 to December 2019. Participants were retrospectively followed to determine the progression of their disease, and their 2-year progress was examined with survival analysis, especially regarding whether they had postoperative relapse (i.e., DFS) or had died since being diagnosed (i.e., OS). The data were processed with a chi-square test and Kaplan-Meier test, with significance set at p < 0.05.

Result: The overexpression of Ki67 correlated significantly with histopathological grade (p = 0.001), tumor size (p = 0.001), DFS (p = 0.001), and OS (p = 0.003).

Conclusion: Ki67's overexpression is significantly correlated with the tumor size, DFS, and OS of patients with breast cancer.

鉴定Ki67是一种识别增殖细胞的单克隆抗体,对于确定乳腺癌患者的增殖活性水平非常重要。我们的研究目的是评估Ki67的表达与乳腺癌患者的组织病理学分级、肿瘤大小、无病生存期(DFS)和总生存期(OS)的相关性。方法:我们的回顾性队列研究纳入了2018年1月至2019年12月在我院就诊的114例乳腺癌患者。回顾性随访参与者以确定其疾病的进展,并通过生存分析检查他们的2年进展,特别是关于他们是否有术后复发(即DFS)或自诊断以来死亡(即OS)。资料采用卡方检验和Kaplan-Meier检验,显著性p < 0.05。结果:Ki67过表达与组织病理分级(p = 0.001)、肿瘤大小(p = 0.001)、DFS (p = 0.001)、OS (p = 0.003)相关。结论:Ki67过表达与乳腺癌患者肿瘤大小、DFS、OS有显著相关性。
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引用次数: 0
Discordance in clinical versus pathological staging in breast cancer: Are we undermining the significance of accurate preoperative staging in the present era? 乳腺癌临床与病理分期的不一致:我们是否削弱了准确的术前分期在当今时代的重要性?
Pub Date : 2022-01-01 DOI: 10.3233/BD-201029
Shina Goyal, Linu Abraham Jacob, D Lokanatha, M C Suresh Babu, K N Lokesh, A H Rudresha, Smitha Saldanha, Usha Amirtham, Antony G F Thottian, L K Rajeev

Background: The present era of individualized treatment for breast cancer is influenced by the initial disease status including the anatomical extent, grade, and receptor status. An accurate preoperative staging is the basis of treatment planning and prognostication. Our study aims to determine the discordance between the preoperative clinical and the postoperative pathological stages of breast cancer patients.

Methodology: The medical records of all non-metastatic breast cancer patients from January 2017 to December 2018 who underwent upfront surgery were reviewed. They were staged as per the eighth AJCC and the concordance between the clinical (c) and pathological T (tumor), N (nodal), and final AJCC stage was studied. A Chi-square test was used to determine factors that significantly correlate with disease discordance.

Results: A total of 307 breast cancer patients were analyzed. Among these, 43.3% were hormone receptor-positive, 30.6% were Her2 positive and 26% were triple-negative. Overall stage discordance was seen in 48.5% (n = 149) patients (upstaging in 22.1%, downstaging in 26.4%). The discordance rate was 48.9% for T stage (cT versus pT) and 57.4% for N stage (cN versus pN). Among patients with clinically node-negative disease, 53.4% were found to have positive nodes on histopathology, while 27.2% had vice versa. Overall, the factors associated with upstaging were ER-positive, Her2 positive and triple-negative status (all p < 0.05), while none of the factors showed significant association with downstaging.

Conclusions: About half of breast cancer patients had discordance between clinical and pathological staging with higher discordance in the nodal stage. This changes the disease prognosis, and may also affect the offered surgical treatment and radiotherapy. Thus highlighting the need for a precise pre-operative staging. Also, this information will aid clinicians in discussions with patients, keeping in mind the likelihood of change in disease staging and management.

背景:乳腺癌的个体化治疗受到初始疾病状态的影响,包括解剖程度、分级和受体状态。准确的术前分期是治疗计划和预后的基础。我们的研究旨在确定乳腺癌患者术前临床分期与术后病理分期之间的不一致性。方法:回顾2017年1月至2018年12月接受前期手术的所有非转移性乳腺癌患者的医疗记录。按照第8期AJCC分期,研究临床(c)与病理T(肿瘤)、N(淋巴结)、最终AJCC分期的一致性。采用卡方检验确定与疾病不一致性显著相关的因素。结果:共分析了307例乳腺癌患者。其中激素受体阳性43.3%,Her2阳性30.6%,三阴性26%。48.5% (n = 149)患者出现总体分期不一致(分期上升为22.1%,分期下降为26.4%)。T期(cT vs pT)不一致率为48.9%,N期(cN vs pN)不一致率为57.4%。在临床淋巴结阴性的患者中,组织病理学上淋巴结阳性的占53.4%,反之占27.2%。总体而言,与抢先期相关的因素有er阳性、Her2阳性和三阴性状态(均为p)。结论:约有一半的乳腺癌患者临床分期与病理分期不一致,其中淋巴结分期不一致程度更高。这改变了疾病的预后,也可能影响所提供的手术治疗和放疗。因此强调了精确的术前分期的必要性。此外,这些信息将有助于临床医生与患者讨论,记住疾病分期和管理变化的可能性。
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引用次数: 4
Relationship between endocrine resistance and the periods of adjuvant endocrine treatment for hormone receptor-positive, HER2-negative breast cancer. 激素受体阳性、her2阴性乳腺癌的内分泌抵抗与辅助内分泌治疗周期的关系
Pub Date : 2022-01-01 DOI: 10.3233/BD-210027
Jun Yamamura, Yukiko Miyamura, Shunji Kamigaki, Junya Fujita, Hiroki Osato, Hironobu Manabe, Yumiko Tanaka, Wataru Shinzaki, Yukihiko Hahimot, Toshikazu Ito, Yoshifumi Komoike

Background: Current guidelines define primary and secondary endocrine resistance according to the periods of adjuvant endocrine therapy (adj-ET); however, the relationship between adj-ET period and endocrine resistance remains unclear.

Objective: We examined progression-free survival (PFS) after primary ET for recurrent hormone receptor-positive/HER2-negative breast cancer, and evaluated the relationship between endocrine resistance and the periods of adj-ET.

Methods: We assessed PFS among 183 patients who received ET as primary treatment for the first recurrence, according to the period of adj-ET (adj-ET < 1 year, 1-2 years, ≥2 years, and completion).

Results: Patients who relapsed during the first year of adj-ET had the significantly shortest PFS. PFS did not significantly differ between patients who relapsed at 1-2 years of adj-ET and patients who relapsed while on adj-ET but after the first 2 years.

Conclusions: Relapse at 1-2 years after adj-ET initiation might be better classified as secondary endocrine resistance rather than primary endocrine resistance.

背景:目前的指南根据辅助内分泌治疗(adjet)的时间来定义原发性和继发性内分泌抵抗;然而,et期与内分泌抵抗的关系尚不清楚。目的:研究复发性激素受体阳性/ her2阴性乳腺癌原发性ET治疗后的无进展生存期(PFS),并评估内分泌抵抗与ET治疗时间之间的关系。方法:我们评估了183例首次复发接受ET作为主要治疗的患者的PFS,根据ET的持续时间(ET < 1年,1-2年,≥2年和完成)。结果:在adj-ET治疗的第一年复发的患者PFS明显最短。在adj-ET治疗1-2年复发的患者和adj-ET治疗2年后复发的患者之间,PFS无显著差异。结论:adj-ET开始治疗后1-2年的复发可能更适合归类为继发性内分泌抵抗而不是原发性内分泌抵抗。
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引用次数: 0
Systematic review and meta-analysis of the papillomavirus prevalence in breast cancer fresh tissues. 乳头瘤病毒在乳腺癌新鲜组织中流行的系统评价和荟萃分析。
Pub Date : 2022-01-01 DOI: 10.3233/BD-201032
Geilson Gomes de Oliveira, Ana Katherine Gonçalves, José Eleutério, Luiz Gonzaga Porto Pinheiro

Background: Although widely studied, the role of HPV in the genesis of breast carcinomas remains elusive due to the diversity of results across studies, possibly caused by the wide methodological heterogeneity, some of them with inadequate methods.

Objective: To verify the association between HPV and breast cancer through the meta-analysis of studies that used the best-recognized techniques for viral detection and tissue conservation.

Methods: A systematic review and meta-analysis restricted to studies that detected HPV by PCR in fresh and frozen tissue from breast cancer were conducted to obtain greater homogeneity. PubMed, Scopus, Science Direct, Cochrane Library, and SciELO were searched until December 14, 2019. Search terms included "breast cancer" and "HPV" without language restrictions. Eleven studies were included in the meta-analysis. The pooled relative risks and 95% confidence interval (95% CI) were calculated, and heterogeneity was assessed using the I-squared (I2).

Results: The selected studies had very low heterogeneity (2%). There is a 2.15 times higher combined relative risk (95% CI = 1.60-2.89) of detecting HPV in breast cancer than in cancer-free breast controls with a statistically significant p-value (p < 0.0001).

Conclusion: Our data support the association of DNA-HPV with breast carcinomas. Further studies are needed to find out which breast cancer subtypes this association is most frequent.

背景:虽然被广泛研究,但由于研究结果的多样性,HPV在乳腺癌发生中的作用仍然难以捉摸,这可能是由于方法的广泛异质性,其中一些方法不充分。目的:通过对使用公认的病毒检测和组织保存技术的研究进行荟萃分析,验证HPV与乳腺癌之间的关联。方法:系统回顾和荟萃分析仅限于用PCR检测乳腺癌新鲜和冷冻组织中HPV的研究,以获得更大的同质性。PubMed、Scopus、Science Direct、Cochrane Library和SciELO被检索到2019年12月14日。搜索词包括“乳腺癌”和“HPV”,没有语言限制。荟萃分析纳入了11项研究。计算合并相对风险和95%置信区间(95% CI),并使用i²(I2)评估异质性。结果:所选研究的异质性非常低(2%)。在乳腺癌中检测到HPV的联合相对危险度(95% CI = 1.60-2.89)是无癌乳腺癌对照组的2.15倍,p值有统计学意义(p)。结论:我们的数据支持DNA-HPV与乳腺癌的关联。需要进一步的研究来找出这种关联最常见的乳腺癌亚型。
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引用次数: 1
Literature review and case report of bilateral intracystic papillary carcinoma associated with an invasive ductal carcinoma in a male breast. 男性双侧囊内乳头状癌合并浸润性导管癌的文献回顾及病例报告。
Pub Date : 2022-01-01 DOI: 10.3233/BD-210001
Fiona Avau, Marie Chintinne, Sarah Baudry, Frédéric Buxant

Intracystic papillary carcinoma (IPC) is a rare tumor with good prognosis that occurs in only 5% to 7.5% of male breast cancer. We report a case of a 46-year-old man who presented a brown nipple discharge a few months ago. He had a bilateral IPC and an invasive ductal carcinoma on the right breast. A double mastectomy was then performed with a bilateral sentinel lymph node biopsy, and he received chemotherapy, radiotherapy, and hormonotherapy. Two years after the diagnosis, the patient recovered and was free of recurrence. Considering the scarcity of this tumor type, we conducted a systematic literature review on the PubMed of all the cases of IPC in men. The clinical presentation, imaging, and treatment of the 43 case reports from the 41 articles selected were described. Furthermore, no clear guidelines for IPC management are available. Conservative surgery should also be preferred, and a sentinel lymph node biopsy should be performed systematically. Moreover, radiotherapy should be proposed in the case of conservative surgery, and hormone therapy could be proposed in the case of invasive IPC or IPC associated with a ductal carcinoma in situ.

囊内乳头状癌(IPC)是一种预后良好的罕见肿瘤,仅占男性乳腺癌的5%至7.5%。我们报告一个病例46岁的男子谁提出了一个棕色乳头溢液几个月前。他患有双侧IPC和右乳浸润性导管癌。然后行双侧乳房切除术,双侧前哨淋巴结活检,并接受化疗、放疗和激素治疗。确诊两年后,患者痊愈,无复发。考虑到这种肿瘤类型的稀缺性,我们在PubMed上对所有男性IPC病例进行了系统的文献回顾。本文描述了41篇文章中43例病例报告的临床表现、影像学和治疗方法。此外,IPC管理没有明确的指导方针。保守手术也是首选,并应系统地进行前哨淋巴结活检。此外,保守手术的情况下应建议放疗,侵袭性IPC或IPC合并导管原位癌的情况下可建议激素治疗。
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引用次数: 3
Breast cancer stem cell population in different molecular subtypes of breast cancer. 乳腺癌干细胞群在不同分子亚型乳腺癌中的作用。
Pub Date : 2022-01-01 DOI: 10.3233/BD-210050
Parul Gupta, Vikram Singh, Sandeep Kumar, Ashim Das, Gurpreet Singh, Amanjit Bal

Background: Breast cancer heterogeneity is well documented and to some extent is attributed to the presence of cancer stem cells (CSCs). Breast cancer stem cells are identified by the presence of cell surface molecule CD44 and absence of CD24.

Methods: In the present study a flowcytometric analysis was done to study the expression distribution of CSC phenotype of CD44+/CD24-/low, among different molecular subtypes of breast cancer and to find a correlation with clinicopathological features.

Results: CSCs were observed in all the molecular subtypes of breast cancer. The highest population of CSCs was noted in luminal B (3.4%), followed by TNBC (1.7%), and Her-2 subtype (1.6%). The least number of CD44+/CD24- cells were seen in Luminal A subgroup (1.3%).

Conclusion: Existence of cancer stem cells in all the subtypes may suggest the possibility of failure of current therapies in treatment of patients.

背景:乳腺癌的异质性已被充分证明,在某种程度上归因于癌症干细胞(CSCs)的存在。乳腺癌干细胞是通过细胞表面分子CD44的存在和CD24的缺失来识别的。方法:采用流式细胞术研究CSC表型CD44+/CD24-/low在乳腺癌不同分子亚型中的表达分布,并探讨其与临床病理特征的相关性。结果:在乳腺癌的所有分子亚型中均可见到CSCs。CSCs最多的是luminal B(3.4%),其次是TNBC(1.7%)和Her-2亚型(1.6%)。CD44+/CD24-细胞数量最少的是Luminal A亚组(1.3%)。结论:肿瘤干细胞在所有亚型中的存在可能提示当前治疗方法在治疗患者时失败的可能性。
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引用次数: 4
Erratum to: Recent advances in the epidemiology of inflammatory breast cancer. 炎性乳腺癌流行病学的最新进展。
Pub Date : 2022-01-01 DOI: 10.3233/BD-210914
Paul H Levine, Carmela C Veneroso
{"title":"Erratum to: Recent advances in the epidemiology of inflammatory breast cancer.","authors":"Paul H Levine,&nbsp;Carmela C Veneroso","doi":"10.3233/BD-210914","DOIUrl":"https://doi.org/10.3233/BD-210914","url":null,"abstract":"","PeriodicalId":9224,"journal":{"name":"Breast disease","volume":" ","pages":"163"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39852665","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Role of MRI in predicting response to neo-adjuvant systemic therapy (NAST) in breast cancer. MRI在预测乳腺癌新辅助全身治疗(NAST)应答中的作用。
Pub Date : 2022-01-01 DOI: 10.3233/BD-210023
Sadaf Jafferbhoy, Manoj Gowda S, Kirti Katherine Kabeer, Zatinahhayu Mohd-Isa, Seema Salehi-Bird, Sekhar Marla, Sankaran Narayanan, Soni Soumian

Background and objectives: MRI is generally performed to assess response to Neo-adjuvant systemic therapy (NAST) in breast cancer.

Objective: To assess role of MRI in determining the probability of having residual disease in patients undergoing NAST. We also evaluated synchronous cancers diagnosed following MRI.

Methods: This is a retrospective study which included all patients who had pre-and post-NAST MRI between June 2014 and December 2019. Data on demographics, tumour characteristics and pathology were collected and analysed. Pre- and post-MRI probability were calculated and depicted on nomograms.

Results: The study included 205 patients. Overall pre-MRI probability of having residual disease was 55% (OR:1.2). The post-MRI probability was 78% (95% CI 72-83%; OR:3.5) if MRI showed residual disease and 23% (95% CI 16-31%, OR:0.3) if imaging showed complete response. The absolute benefit was higher in TNBC and HR-HER2. Additional cancers were identified in 8.78% of patients.

Conclusion: MRI is beneficial in evaluating response to NAST specifically in TNBC and HR-HER2 cancers. Pre- and post-MRI probabilities of residual disease depicted on nomograms are a useful tool for clinicians. MRI can potentially impact the treatment decisions by identification of synchronous cancers.

背景和目的:MRI通常用于评估乳腺癌患者对新辅助全身治疗(NAST)的反应。目的:探讨核磁共振成像(MRI)在确定NAST患者残留病变概率中的作用。我们也评估了MRI诊断的同步癌。方法:这是一项回顾性研究,纳入了2014年6月至2019年12月期间所有接受过nast MRI前后的患者。收集和分析了人口统计学、肿瘤特征和病理数据。计算了mri前后的概率并在图上进行了描述。结果:纳入205例患者。总体mri前病变残留概率为55% (OR:1.2)。mri后的概率为78% (95% CI 72-83%;如果MRI显示残留病变,OR为3.5),如果影像学显示完全缓解,OR为23% (95% CI 16-31%, OR:0.3)。TNBC和HR-HER2的绝对获益更高。在8.78%的患者中发现了其他癌症。结论:MRI有助于评估TNBC和HR-HER2肿瘤对NAST的反应。造影图上描述的mri前和mri后残留疾病的概率是临床医生的有用工具。MRI可以通过识别同步性癌症来潜在地影响治疗决策。
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引用次数: 1
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Breast disease
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