Breast Carcinoma

乳腺癌
  • 文章类型: Journal Article
    背景:早期乳腺癌(BC)迫切需要创新的治疗策略。源自乳腺导管细胞的肿瘤提供了靶向干预的机会。方法:我们探索了通过自然乳头开口进行导管内治疗作为早期BC的一种有希望的非侵入性方法。使用功能性近红外II(NIR-II)纳米材料,特别是NIR-IIb量子点与Epep多肽缀合,用于导管细胞靶向,我们对乳腺导管进行了原位成像和光热消融。导管内给药之后用808nm激光进行刺激。结果:该方法在微环境中实现了精确的导管破坏和增强的免疫反应。该技术在三阴性BC小鼠模型和导管原位癌大鼠模型中得到了验证,证明了局部BC治疗和预防的有希望的治疗潜力。结论:我们的研究证明了NIR-II纳米探针在引导乳腺导管的非侵入性光热消融中的有效性,为早期BC治疗提供了一条引人注目的途径。
    Background: Innovative treatment strategies for early-stage breast cancer (BC) are urgently needed. Tumors originating from mammary ductal cells present an opportunity for targeted intervention. Methods: We explored intraductal therapy via natural nipple openings as a promising non-invasive approach for early BC. Using functional Near-infrared II (NIR-II) nanomaterials, specifically NIR-IIb quantum dots conjugated with Epep polypeptide for ductal cell targeting, we conducted in situ imaging and photothermal ablation of mammary ducts. Intraductal administration was followed by stimulation with an 808 nm laser. Results: This method achieved precise ductal destruction and heightened immunological responses in the microenvironment. The technique was validated in mouse models of triple-negative BC and a rat model of ductal carcinoma in situ, demonstrating promising therapeutic potential for localized BC treatment and prevention. Conclusion: Our study demonstrated the effectiveness of NIR-II nanoprobes in guiding non-invasive photothermal ablation of mammary ducts, offering a compelling avenue for early-stage BC therapy.
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  • 文章类型: Case Reports
    皮肤转移很少见,但可能表明晚期内部恶性肿瘤或先前治疗过的恶性肿瘤复发,通常与预后不良有关。由于临床表现是可变且非特异性的,因此它们也可能构成诊断问题。可以模仿其他良性条件。我们报告了一例48岁的女性,她的躯干上有4年的红斑丘疹和囊泡病史,模仿了淋巴管瘤。皮肤活检和免疫组织化学与乳腺癌皮肤转移一致。皮肤转移表现为多种模式。高度怀疑和皮肤活检的低阈值对于早期诊断和治疗至关重要。组织病理学评估将有助于确定皮肤转移的起源,并且可以显着影响治疗的结果。
    Cutaneous metastasis is rare but may indicate an advanced internal malignancy or a recurrence of a previously treated one and is usually associated with a poor prognosis. They may also pose a diagnostic problem as the clinical manifestations are variable and non-specific, which could mimic other benign conditions. We report a case of a 48-year-old female who presented with a 4-year history of erythematous papules and vesicles on the trunk mimicking lymphangioma circumscriptum. Skin biopsy and immunohistochemistry were consistent with cutaneous metastasis from breast carcinoma. Cutaneous metastasis presents in a variety of patterns. A high index of suspicion and a low threshold for skin biopsy are paramount to the early diagnosis and treatment. A histopathologic evaluation will help identify the origin of the cutaneous metastasis and can significantly affect the outcome of the treatment.
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  • 文章类型: Journal Article
    肢端转移很少见。小于0.01%的患者在足骨有转移。足部多骨性转移极为罕见。我们报告了一名50岁的女性,她在右乳房根治术4年后抱怨右脚进行性疼痛和肿胀。[18F]FDGPET/CT显示右脚多处混合性骨破坏,[18F]FDGPET/CT强烈摄取。CT引导下的跟骨活检证实了转移性乳腺癌的诊断。
    Acrometastases are rare. Less than 0.01% of patients have metastasis in the foot bone. Polyostotic metastasis in the foot is extremely rare. We report a 50-year-old woman who complained of progressive pain and swelling in the right foot after radical right mastectomy for 4 years. [18F]FDG PET/CT demonstrated multiple mixed bone destruction in the right foot with intense [18F]FDG PET/CT uptake. CT-guided calcaneus biopsy confirmed the diagnosis of metastatic breast carcinoma.
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  • 文章类型: Journal Article
    乳腺癌(BC)是全球女性中最常见的恶性肿瘤,高转移率是肺癌后死亡的主要原因。目前,他莫昔芬(TAM)是一种疏水性抗癌剂和选择性雌激素调节剂(SERM),由FDA批准,已显示出针对BC的潜在抗癌活性,但是非定向递送具有严重的副作用,限制了其无处不在的效用。因此,将抗癌药物精确释放到肿瘤部位,可以提高疗效,减少对身体的副作用。纳米技术已成为解决过量TAM毒性问题的最重要策略之一,由于纳米使能的制剂能够在更长的时间内向癌细胞递送所需量的TAM。鉴于此,在靶向药物递送中使用荧光碳纳米颗粒为提高疗效提供了新的希望,安全,和TAM治疗的特异性。这里,我们合成的生物相容性碳纳米颗粒(CNPs)使用壳聚糖分子没有任何有毒的表面钝化剂。合成的CNP表现出良好的水分散性,并且在激发(360nm源)时发出强烈的蓝色荧光。已经使用点击化学用叶酸将CNP的表面官能化,以改善恶性细胞的靶向药物摄取。成功利用癌细胞和正常细胞之间的pH差异来触发靶位点的TAM释放。经过6个小时的孵化,CNP在酸性pH下释放约74%的TAM药物。体外,研究还表明,用合成的CNPs治疗后,可以实现对肿瘤生长的显著抑制。
    Breast cancer (BC) is the most common malignancy among females worldwide, and its high metastasis rates are the leading cause of death just after lung cancer. Currently, tamoxifen (TAM) is a hydrophobic anticancer agent and a selective estrogen modulator (SERM), approved by the FDA that has shown potential anticancer activity against BC, but the non-targeted delivery has serious side effects that limit its ubiquitous utility. Therefore, releasing anti-cancer drugs precisely to the tumor site can improve efficacy and reduce the side effects on the body. Nanotechnology has emerged as one of the most important strategies to solve the issue of overdose TAM toxicity, owing to the ability of nano-enabled formulations to deliver desirable quantity of TAM to cancer cells over a longer period of time. In view of this, use of fluorescent carbon nanoparticles in targeted drug delivery holds novel promise for improving the efficacy, safety, and specificity of TAM therapy. Here, we synthesized biocompatible carbon nanoparticles (CNPs) using chitosan molecules without any toxic surface passivating agent. Synthesized CNPs exhibit good water dispersibility and emit intense blue fluorescence upon excitation (360 nm source). The surface of the CNPs has been functionalized with folate using click chemistry to improve the targeted drug uptake by the malignant cell. The pH difference between cancer and normal cells was successfully exploited to trigger TAM release at the target site. After six hours of incubation, CNPs released ∼ 74 % of the TAM drug in acidic pH. In vitro, studies have also demonstrated that after treatment with the synthesized CNPs, significant inhibition of the tumor growth could be achieved.
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  • 文章类型: Case Reports
    多形性癌(PC)是一种罕见的高级乳腺癌形式,其特征是存在独特的多形性巨大肿瘤细胞,表现出奇异的核和非典型的有丝分裂。在这项研究中,我们报告了3例患者,他们在显微镜下出现了由大型多形性细胞增生组成的病变,其中多核巨细胞占优势。免疫组织化学分析显示,在各个恶性成分中具有不同的免疫学特征。值得注意的是,这份报告旨在提供有价值的见解,增加了对这种罕见肿瘤的理解,伴随着文献综述。尽管它很罕见,由于其独特的形态学和病理学特征,乳腺中的PC仍然具有临床相关性。这些独特的属性需要在临床表现和管理方面进行具体考虑。
    Pleomorphic carcinoma (PC) is an uncommon and high-grade form of breast carcinoma characterized by the presence of distinctive pleomorphic giant tumor cells exhibiting bizarre nuclei and atypical mitosis. In this study, we report three patients who presented with lesions composed of a proliferation of large pleomorphic cells with a predominance of multinucleated giant cells on a microscope. Immunohistochemical analysis revealed distinct immunologic profiles within the respective malignant components. Notably, this report aims to contribute valuable insights, adding to the understanding of this uncommon tumor, accompanied by a literature review. Despite its rarity, PC in the breast remains clinically relevant due to its distinctive morphological and pathological features. These unique attributes require specific considerations in both clinical presentation and management.
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  • 文章类型: Journal Article
    乳腺癌(BRCA)是一种危及女性生命的恶性肿瘤,预后不良。角化是一种新的细胞死亡模式,但其与BRCA的关系尚不清楚。这项研究试图开发BRCA的角化相关预后基因标签。
    通过共识聚类获得BRCA的角化相关亚型。差异表达分析使用\'limma\'包实施。进行单变量Cox和多变量Cox分析以确定角化相关的预后基因签名。在不同的数据集中构建和验证签名。还使用预后标签进行基因集变异分析(GSVA)和基因集富集分析(GSEA),以揭示潜在的分子机制。应用ESTIMATE和CIBERSORT算法来探测基因标签和肿瘤微环境(TME)之间的联系。使用肿瘤免疫功能障碍和排除(TIDE)网络工具评估免疫治疗反应性。采用实时定量PCR(RT-qPCR)技术检测乳腺癌细胞株中与角化相关的预后基因的表达。
    通过共识聚类和差异表达分析,挖掘了BRCA中38个与角化相关的差异表达基因(DEGs)。基于单变量Cox和多变量Cox分析,六个与角化相关的预后基因,即SAA1、KRT17、VAV3、IGHG1、TFF1和CLEC3A,被挖掘以建立相应的签名。已使用外部验证集验证签名。GSVA和GSEA表明,多个细胞周期相关和免疫相关途径以及生物学过程与签名相关。ESTIMATE和CIBERSORT分析的结果显示,两个Cumsig评分亚组之间的TME存在显着差异。最后,细胞系的RT-qPCR分析进一步证实了SAA1、KRT17、IGHG1和CLEC3A的表达趋势。
    放在一起,我们构建了一个标记来预测BRCA患者的总体生存率,并且我们的发现验证了与角化相关的预后基因,这有望为开发预后性分子生物标志物和深入了解杯突与BRCA之间的关系提供基础。
    UNASSIGNED: Breast carcinoma (BRCA) is a life-threatening malignancy in women and shows a poor prognosis. Cuproptosis is a novel mode of cell death but its relationship with BRCA is unclear. This study attempted to develop a cuproptosis-relevant prognostic gene signature for BRCA.
    UNASSIGNED: Cuproptosis-relevant subtypes of BRCA were obtained by consensus clustering. Differential expression analysis was implemented using the \'limma\' package. Univariate Cox and multivariate Cox analyses were performed to determine a cuproptosis-relevant prognostic gene signature. The signature was constructed and validated in distinct datasets. Gene set variation analysis (GSVA) and gene set enrichment analysis (GSEA) were also conducted using the prognostic signature to uncover the underlying molecular mechanisms. ESTIMATE and CIBERSORT algorithms were applied to probe the linkage between the gene signature and tumor microenvironment (TME). Immunotherapy responsiveness was assessed using the Tumor Immune Dysfunction and Exclusion (TIDE) web tool. Real-time quantitative PCR (RT-qPCR) was performed to detect the expressions of cuproptosis-relevant prognostic genes in breast cancer cell lines.
    UNASSIGNED: Thirty-eight cuproptosis-associated differentially expressed genes (DEGs) in BRCA were mined by consensus clustering and differential expression analysis. Based on univariate Cox and multivariate Cox analyses, six cuproptosis-relevant prognostic genes, namely SAA1, KRT17, VAV3, IGHG1, TFF1, and CLEC3A, were mined to establish a corresponding signature. The signature was validated using external validation sets. GSVA and GSEA showed that multiple cell cycle-linked and immune-related pathways along with biological processes were associated with the signature. The results ESTIMATE and CIBERSORT analyses revealed significantly different TMEs between the two Cusig score subgroups. Finally, RT-qPCR analysis of cell lines further confirmed the expressional trends of SAA1, KRT17, IGHG1, and CLEC3A.
    UNASSIGNED: Taken together, we constructed a signature for projecting the overall survival of BRCA patients and our findings authenticated the cuproptosis-relevant prognostic genes, which are expected to provide a basis for developing prognostic molecular biomarkers and an in-depth understanding of the relationship between cuproptosis and BRCA.
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  • 文章类型: Journal Article
    背景:临床试验数据表明,对于精心选择的临床淋巴结阳性乳腺癌患者,在新辅助化疗(NCT)后达到病理完全缓解(pCR),省略腋窝淋巴结清扫术(ALND)是可行的,并且可以降低发病率。然而,仍然需要了解这些发现如何转化为更广泛的临床实践,并确定哪些患者受益最大.本研究利用国家数据集来评估腋窝管理的结果,旨在为腋窝降级提供最佳实践。
    方法:国家癌症数据库用于识别2012年至2020年间诊断为临床淋巴结阳性浸润性乳腺癌并接受NCT和随后的ALND的女性。对临床病理因素与腋窝pCR的关系进行统计学分析。
    结果:在59,791名患者中,8,827(14.76%)实现了节点pCR。HR阴性和HER2阳性受体状态的患者更频繁地接受ALND而不是前哨淋巴结活检。相反,70岁以上的患者,有私人或公共保险的患者,分类为ypT1或ypT2的病例不太可能接受ALND。
    结论:一部分临床淋巴结阳性乳腺癌患者接受了ALND,尽管在NCT后达到了腋窝pCR。这凸显了提高识别腋窝降级候选者的准确性的机会,有可能降低发病率,并根据个体患者的需求调整治疗方案。
    BACKGROUND: Clinical trial data indicate that omitting axillary lymph node dissection (ALND) is feasible and may reduce morbidity for carefully selected patients with clinically node-positive breast cancer who achieve a pathological complete response (pCR) after neoadjuvant chemotherapy (NCT). However, there remains a need to understand how these findings translate to broader clinical practice and to identify which patients benefit most. This study utilizes a national dataset to assess outcomes in axillary management, aiming to inform best practice in axillary de-escalation.
    METHODS: The National Cancer Data Base was used to identify women diagnosed with clinically node-positive invasive breast cancer between 2012 to 2020 who received NCT and subsequent ALND. Associations between clinicopathologic factors and axillary pCR were analyzed statistically.
    RESULTS: Of the 59,791 patients included, 8,827 (14.76%) achieved nodal pCR. Patients with HR-negative and HER2-positive receptor status more frequently underwent ALND instead of sentinel lymph node biopsy. Conversely, patients over the age of 70, those with private or public insurance, and cases classified as ypT1 or ypT2 were less likely to undergo ALND.
    CONCLUSIONS: A subset of patients with clinically node-positive breast cancer received ALND despite achieving axillary pCR following NCT. This highlights an opportunity to enhance precision in identifying candidates for axillary de-escalation, potentially reducing morbidity and tailoring treatment more closely to individual patient needs.
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  • 文章类型: Journal Article
    背景:我们进行了这项研究,以确定剂量学特性,例如放疗期间的平均和最大辐射剂量以及食道的辐射暴露程度。这些因素可能会影响接受锁骨上放疗的乳腺癌患者食管炎的发展。
    方法:从2023年1月至6月,在孟加拉国的BangabandhuSheikhMujib医科大学进行了一项观察性研究。患者对胸壁和锁骨上淋巴结接受放射治疗(15个部位为40.05Gy),为期三周。我们能够从剂量体积直方图(DVH)数据中猜测以下内容:治疗区域的食道长度(即,在计划CT扫描中可见的食道大小),最大剂量(Dmax),平均剂量(Dmean),以及给予食道的10Gy(V10Gy)和20Gy(V20Gy)剂量的体积。放疗期间,患者每周检查一次,结果:左侧乳腺癌患者表现出更高的Dmean,Dmax,与右侧乳腺癌患者相比,食道的长度。具体来说,Dmean为6.7(±2.1)Gy,Dmax为39.2(±1.5)Gy,食管长度为6.1(±1.2)Gy。左乳腺癌患者食管V10Gy和V20Gy值升高,但差异无统计学意义。右侧乳腺癌和左侧乳腺癌的V10Gy发生率分别为4.2%(±2.6%)和19.8%(±9.2%),分别。右侧乳腺癌的V20Gy为2.4%(±0.9%),左侧乳腺癌的V20Gy为13.09%(±5.0%)。结论:总之,在患有乳腺癌和急性食管炎的女性患者中,平均食道剂量与手术后左锁骨上区域的放射量有很强的相关性.我们可以通过处方剂量限制和精确描绘食道来减少食道毒性。
    BACKGROUND: We conducted this investigation to ascertain the dosimetric properties such as the mean and maximum radiation dosage during radiotherapy as well as the extent of radiation exposure to the esophagus. These factors can potentially impact the development of esophagitis in breast cancer patients undergoing supraclavicular radiation.
    METHODS:  From January to June 2023, an observational study was conducted at Bangabandhu Sheikh Mujib Medical University in Bangladesh. The patients received radiation therapy (40.05 Gy in 15 parts) to the chest wall and supraclavicular node for three weeks. We were able to guess the following from the dose volume histogram (DVH) data: the length of the esophagus in the treatment area (i.e., the size of the esophagus that was visible on the planning CT scan), the maximum dose (Dmax), the mean dose (Dmean), and the volume of the 10Gy (V10Gy) and 20Gy (V20Gy) doses that were given to the esophagus. During radiotherapy, patients were checked on once a week, and the radiotherapy oncology group was used to evaluate and grade esophagitis Results: Patients with left-sided breast cancer showed a higher Dmean, Dmax, and length of the esophagus compared to those with right-sided breast cancer. Specifically, the Dmean was 6.7 (±2.1) Gy, the Dmax was 39.2 (±1.5) Gy, and the length of the esophagus was 6.1 (±1.2) Gy. Patients with left breast cancer had elevated V10Gy and V20Gy values for the esophagus, but the difference was not statistically significant. The incidence of V10Gy for right-sided breast cancer and left-sided breast cancer was 4.2% (±2.6%) and 19.8% (±9.2%), respectively. The V20Gy was 2.4% (±0.9%) for right-sided breast cancer and 13.09% (±5.0%) for left-sided breast cancer Conclusion: In conclusion, there is a strong association between the mean oesophageal dose and radiation to the left supraclavicular region following surgery in women with breast cancer and acute esophagitis. We can reduce esophageal toxicity by prescribing dose restrictions and performing precise delineation of the esophagus.
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  • 文章类型: Journal Article
    目的:TP53突变的重要性已在几种肿瘤类型中得到证实,包括乳腺癌(BC)。然而,p53蛋白表达作为基因突变预测因子的准确性在BC中尚未得到很好的研究。因此,我们评估了64例乳腺癌患者中与TP53突变相关的p53蛋白表达.
    方法:使用下一代测序(NGS)检查TP53突变。使用免疫组织化学(IHC)检查p53蛋白表达。
    结果:在64个BC中,55%表现出异常表达模式,包括27%的过表达,22%null,6%模棱两可,45%具有野生型模式。TP53突变存在于53%(34/64)的肿瘤中,包括30%(19/64)显示错义突变,11%(7/64)具有移码突变,11%(7/64)具有无义突变,3%(1/64)具有剪接位点突变。p53蛋白的异常表达在34个携带TP53突变的肿瘤中有33个(97%)存在;相反,30例肿瘤中有28例(93%)存在野生型模式,但没有可检测到的突变(p<0.0001).大多数具有p53IHC过表达模式的BC(15/17,88%)含有错义TP53突变;而大多数具有无效模式的BC(12/14,86%)含有截短突变(p<0.0001)。当与显示过表达的那些相比时,具有无效模式的BC与高诺丁汉组织学分级和三阴性表型相关(p<0.05)。
    结论:这些研究结果表明p53IHC可能是BC中TP53突变的潜在替代。不同的p53表达模式可能与BC中特定的TP53基因突变相关。
    OBJECTIVE: The importance of a TP53 mutation has been demonstrated in several tumor types, including breast cancer (BC). However, the accuracy of p53 protein expression as a predictor of gene mutation has not been well studied in BC. Therefore, we evaluated p53 protein expression associated with TP53 mutations in breast cancers from 64 patients.
    METHODS: TP53 mutation was examined using next-generation sequencing (NGS). p53 protein expression was examined using immunohistochemistry (IHC).
    RESULTS: Among the 64 BCs, 55% demonstrated abnormal expression patterns including 27% overexpression, 22% null, 6% equivocal with 45% having a wild-type pattern. A TP53 mutation was present in 53% (34/64) of tumors including 30% (19/64) demonstrating a missense mutation, 11% (7/64) with a frameshift mutation, 11% (7/64) with a nonsense mutation, and 3% (1/64) with a splice site mutation. Abnormal expression of p53 protein was present in 33 of 34 (97%) tumors carrying a TP53 mutation; conversely, a wild-type pattern was present in 28 of 30 (93%) tumors without a detectable mutation (p < 0.0001). The majority of BCs with a p53 IHC overexpression pattern (15/17, 88%) contained a missense TP53 mutation; while the majority of BCs with a null pattern (12/14, 86%) contained a truncating mutation (p < 0.0001). The BCs with a null pattern are associated with a high Nottingham histological grade and a triple-negative phenotype when compared to those demonstrating overexpression (p < 0.05).
    CONCLUSIONS: These findings suggest that p53 IHC can be a potential surrogate for TP53 mutations in BC. Different p53 expression patterns may correlate with specific TP53 genetic mutations in BC.
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  • 文章类型: Journal Article
    安装有氧气传感器的细针活检工具用于体内测量肿瘤异种移植物中的氧气水平。该系统提供了测量从特定位置收获的肿瘤组织中的氧含量的手段。在鼠模型中观察到人肿瘤异种移植物中的氧超过1分钟。根据氧张力(pO2)读数绘制组织图,并采样以进行常规细胞学检查。在60秒内对pO2读数进行仔细建模,得出了传感器尖端处氧气的扩散系数,在取样前提供关于组织的额外诊断信息。氧水平测量可以为在肿瘤诊断中使用生物标志物提供有用的辅助。
    An oxygen sensor-mounted fine-needle biopsy tool was used for in vivo measurement of oxygen levels in tumor xenografts. The system provides a means of measuring the oxygen content in harvested tumor tissue from specific locations. Oxygen in human tumor xenografts in a murine model was observed for over 1 min. Tissues were mapped in relation to oxygen tension (pO2) readings and sampled for conventional cytological examination. Careful modeling of the pO2 readings over 60 seconds yielded a diffusion coefficient for oxygen at the sensor tip, providing additional diagnostic information about the tissue before sampling. Oxygen level measurement may provide a useful adjunct to the use of biomarkers in tumor diagnosis.
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