Combination of digital mammography with semi-automated 3D breast ultrasound

This paper describes work aimed at combining 3D ultrasound with full-field digital mammography via a semi-automatic prototype ultrasound scanning mechanism attached to the digital mammography system gantry. Initial efforts to obtain high x-ray and ultrasound image quality through a compression paddle are proving successful. Registration between the x-ray mammogram and ultrasound image volumes is quite promising when the breast is stably compressed. This prototype system takes advantage of many synergies between the co-registered digital mammography and pulse-echo ultrasound image data used for breast cancer detection and diagnosis. In addition, innovative combinations of advanced US and X-ray applications are being implemented and tested along with the basic modes. The basic and advanced applications are those that should provide relatively independent information about the breast tissues. Advanced applications include x-ray tomosynthesis, for 3D delineation of mammographic structures, and non-linear elasticity and 3D color flow imaging by ultrasound, for mechanical and physiological information unavailable from conventional, non-contrast x-ray and ultrasound imaging.     

自动乳腺超声诊断系统在乳腺癌方面的应用进展

自动乳腺超声诊断系统(Automatic breast ultrasound system,ABUS)是近年来乳腺超声检查的一项新技术,具有图像标准化、操作可重复性高以及获得冠状面信息等优点。由于其图像采集与图像解读可独立进行,因此可提高超声医师工作效率。ABUS不仅可用作乳腺癌的筛查工具,在诊断性能上,其高质量的冠状面成像有助于鉴别病变良恶性;自动优化成像还可提高了乳腺病变的检出率。除此之外,它可对乳腺癌分子亚型进行预测,在新辅助化疗效果评估中有一定应用价值。本文对ABUS关于乳腺癌方面的临床应用研究进行综述,并探讨其未来更多应用。     

Digital mammography: a review of technical development and clinical applications

For detecting and diagnosing breast cancer at its earliest stage, mammography is the most sensitive technique currently available and is therefore the method of choice. Screen-film mammography has been used successfully as a screening test for breast cancer for > 2 decades. However, conventional mammography has substantial limitations and, therefore, digital mammography systems have been developed to improve image quality and overcome the limitations of screen-film technique limitations. Herein we discuss the differences between screen-film and digital mammography systems and the processes related to digital mammography that differ from conventional mammography, including detector technology, digital image formation, image processing, image display, and image archival. Finally, we review the results from currently available clinical trials regarding the performance of digital mammography and discuss clinical implications such as cost-effectiveness.     

Detectors for digital mammography

Interest in digital radiography was stimulated by the enthusiastic acceptance of computed tomography in the early 1970s. It quickly became apparent to the medical community that images with improved information content, whose display characteristics could be manipulated by the viewer, provided many advantages. Subsequently, digital systems for subtraction angiography and later for conventional projection radiography and fluoroscopy were developed. The timing of the introduction of these systems was highly dependent on the readiness of certain key component technologies to meet the requirements of each of these applications. These components are the x-ray detectors, analog to digital converters, computers, data storage systems and high-resolution electronic displays and printers used in image acquisition, storage and display. Mammography represents one of the most demanding radiographic applications, simultaneously requiring excellent contrast sensitivity, high spatial resolution, and wide dynamic range at as low as radiation dose to the breast as is reasonably achievable while meeting the other requirements. For this reason, it is one of the last radiographic procedures to "go digital". Here, some of the considerations related to the detector technology for digital mammography will be discussed and systems currently available will be described.     

The Evolving Role of Circulating Tumor Cells in the Personalized Management of Breast Cancer: From Enumeration to Molecular Characterization

Circulating tumor cells (CTCs) represent tumor cells in the blood stream dislodged from the primary tumor. The presence of CTCs in the bloodstream provides a unique opportunity to sample cancer tissue by means of a relatively less-invasive “liquid biopsy.” Over the past decade, there has been a tremendous increase in the amount of research examining the potential clinical utility of CTCs in the management of cancer. A number of techniques to refine the sensitivity and range of CTC assays are also in development. In this article, we review the recent developments in the current and potential clinical applications of CTCs in breast cancer. CTC enumeration already has an established role as a prognostic biomarker in metastatic breast cancer, whereas molecular characterization of CTCs can serve as a potential predictive biomarker for therapy selection, pharmacodynamic evaluation, and identification of novel actionable targets for novel therapies. The role of CTCs in breast cancer screening and detection of recurrence is currently limited. Further development in techniques will be pivotal in enhancing the broad applicability of CTCs and advancing the field of personalized breast cancer therapy.     

Shaping the future of biomarker research in breast cancer to ensure clinical relevance

Each year, over 200,000 people are diagnosed with breast cancer in the United States. Although the use of biomarkers has the potential to guide preventive interventions and improve survival and quality of life, there have been few successes and many disappointments. In November 2005, the National Breast Cancer Coalition Fund convened a conference aimed at developing a patient-centred, strategic approach to breast cancer biomarker research. The consumers, clinicians, researchers, industry representatives and US regulators who served on the consensus panel developed a set of principles and recommendations to guide the field and ensure that biomarker research results in clinically important applications.     

数字乳腺X线摄影应用研究进展

乳腺断层摄影是通过多点投照获得多个层面的重建图像,这种技术能够提高病灶的检出率和诊断的准确性,降低筛查回叫率。在乳腺疾病的诊断与乳腺癌的筛查中均起着重要作用。双能量乳腺增强摄影检查时需给患者注入碘造影剂,并通过高低能量两次曝光获得标准能量图和高低能量减影图,后者能显示有异常的强化区域。这种技术仅用于诊断性检查,跟常规的乳腺X线检查或常规X线检查加超声组合相比,其检出乳腺癌的敏感性更高;与增强乳腺MRI相比,对主病灶判断的特异性较高,敏感性则相当。     

3D breast image registration--a review

Image registration is an important problem in breast imaging. It is used in a wide variety of applications that include better visualization of lesions on pre- and post-contrast breast MRI images, speckle tracking and image compounding in breast ultrasound images, alignment of positron emission, and standard mammography images on hybrid machines et cetera. It is a prerequisite to align images taken at different times to isolate small interval lesions. Image registration also has useful applications in monitoring cancer therapy. The field of breast image registration has gained considerable interest in recent years. While the primary focus of interest continues to be the registration of pre- and post-contrast breast MRI images, other areas like breast ultrasound registration have gained more attention in recent years. The focus of registration algorithms has also shifted from control point based semi-automated techniques, to more sophisticated voxel based automated techniques that use mutual information as a similarity measure. This paper visits the problem of breast image registration and provides an overview of the current state-of-the-art in this area.     

Identification of distinct protein expression patterns in bilateral matched pair breast ductal fluid specimens from women with unilateral invasive breast carcinoma. High-throughput biomarker discovery

BACKGROUND: Analysis of the biochemical and cellular contents of breast ductal fluid has recently gained attention as a potential noninvasive method for studying the local microenvironment associated with the development and progression of breast carcinoma. METHODS: Patients with unilateral primary invasive breast carcinoma were eligible for the current prospective pilot study. Nipple aspiration fluid (NAF) was obtained from the breast with cancer and the normal contralateral breast and subjected to two-dimensional electrophoresis. Computer-assisted image analysis was used to analyze NAF protein expression profiles. RESULTS: The number of separate protein spots detected in NAF samples ranged from 1280 to 1649. Substantial qualitative differences were identified between NAF protein expression patterns in the breast with cancer compared with the breast without cancer. Protein spots detected in the breast with cancer and not in the breast without cancer from the same patient varied from 30 to 202 different proteins. In addition, the number of protein spots detected in the breast without cancer and not in the breast with cancer of the same patient varied from 14 to 73 different proteins. Conversely, in an individual without breast carcinoma, only three protein spots were detected in the left breast but not the right breast, and only two were detected in the right breast but not the left breast. CONCLUSIONS: The breast is a unique organ in that its microenvironment can be readily accessed and evaluated by aspiration of fluid from the nipple. Breast ductal fluid contains a large number of proteins. As breasts are paired organs, comparisons of ductal fluid from a breast with cancer and the same patient's normal contralateral breast may reveal significant differences in protein expression associated with breast carcinoma. Recent advances in image analysis, automated mass spectrometry, and bioinformatics have provided the tools necessary to use ductal fluids from breast carcinoma patients for high-throughput biomarker discovery.     

Big Data Solutions for Controversies in Breast Cancer Treatment

The digital world of data is expanding with an annual growth rate of 40%, and health care is among the fastest growing sector of the digital world with an annual growth rate of 48%. Rapid growth in technology has augmented data generation; for example, electronic health records produce huge amounts of patient-level data, whereas national registries capture information on numerous factors affecting health care delivery and patient outcomes. This big data can be utilized to improve health care outcomes. This review discusses relevant applications in breast cancer treatment.     

Ki67: a time-varying biomarker of risk of breast cancer in atypical hyperplasia

Uncontrolled proliferation is a defining feature of the malignant phenotype. Ki67 is a marker for proliferating cells and is overexpressed in many breast cancers. Atypical hyperplasia is a premalignant lesion of the breast (relative risk ~ 4.0). Here, we asked if Ki67 expression could stratify risk in women with atypia. Ki67 expression was assessed immunohistochemically by digital image analysis in archival sections from 192 women with atypia diagnosed at the Mayo Clinic 1/1/67–12/31/91. Risk factor and follow-up data were obtained via study questionnaire and medical records. Observed breast cancer events were compared to population expected rates (Iowa SEER) using standardized incidence ratios (SIRs). We examined two endpoints: risk of breast cancer within 10 years and after 10 years of atypia biopsy. Thirty-two (16.7%) of the 192 women developed breast cancer over a median of 14.6 years. Thirty percent (58) of the atypias had ≥2% cells staining for Ki67. In these women, the risk of breast cancer within 10 years after atypia was increased (SIR 4.42 [2.21–8.84]) but not in those with <2% staining. Specifically, the cumulative incidence for breast cancer at 10 years was 14% in the high Ki67 vs. 3% in the low Ki67 group. Conversely, after 10 years, risk in the low Ki67 group rose significantly (SIR 5.69 [3.63–8.92]) vs. no further increased risk in the high Ki67 group (SIR 0.78 [0.11–5.55]). Ki67 appears to be a time-varying biomarker of risk of breast cancer in women with atypical hyperplasia.     

肿瘤突变负荷作为乳腺癌免疫治疗的新兴生物标志物的研究进展

随着免疫时代的到来,免疫治疗为乳腺癌提供了新的治疗方法。应用免疫检查点抑制剂(ICI)治疗乳腺癌已经在临床实践中取得了重大进展。但是,这种治疗药物只对少数患者有效,并且可能会导致免疫相关不良事件的发生,因此,必须通过使用相关的生物标志物来优化患者的治疗选择。最近,有研究证实肿瘤突变负荷(TMB)是一种可以预测乳腺癌免疫治疗疗效的新兴生物标记物。本文就TMB在乳腺癌患者免疫治疗疗效中的预测价值与应用现状等方面进行综述。     

基于乳腺X线摄影发现的乳腺病灶与乳腺断层摄影一致性分析

目的:探讨乳腺X线摄影（digital mammography,DM）发现的乳腺病灶与乳腺断层摄影（digital breast tomosynthesis,DBT）诊断乳腺病灶的一致性。方法:回顾性分析来我院进行乳腺癌检查发现乳腺病灶的患者DM和DBT检查资料,对DM、DBT发现的乳腺病灶的最大直径、形态、边缘、密度、深度、象限、钟点方向、距乳头距离、乳腺实质BI-ARDS分类、可疑性钙化分布、可疑性钙化形态及最终分类进行一致性分析。结果:DBT、DM检查共同发现病灶165例,其中可疑性钙化23例,结构扭曲15例,肿块154例,不对称致密60例。两种方法检查乳腺病灶的钟点方向、距乳头距离、象限、深度一致性分别为0.84、0.99、0.85、0.85。两种方法图像特征描述的一致性参数分别为最大直径0.97、形态0.91、边缘0.94、密度0.94。两种方法钙化特征描述的一致性参数可疑性钙化分布0.86、可疑性钙化形态0.94。形态乳腺实质BI-ARDS分类一致性参数为0.95。病灶BI-ARDS分类一致性参数为0.94。结论:在乳腺病灶诊断方面,DBT和DM具有较好的一致性,DBT较DM可以发现更多的乳腺病灶,可作为乳腺X线摄影的补充方法应用于诊断及新辅助化疗疗效评价等方面。     

Digital image analysis of membrane connectivity is a robust measure of HER2 immunostains

The purpose of this study was to develop and validate a new software, HER2-CONNECT^TM, for digital image analysis of the human epidermal growth factor receptor 2 (HER2) in breast cancer specimens. The software assesses immunohistochemical (IHC) staining reactions of HER2 based on an algorithm evaluating the cell membrane connectivity. The HER2-CONNECT^TM algorithm was aligned to match digital image scorings of HER2 performed by 5 experienced assessors in a training set and confirmed in a separate validation set. The training set consisted of 167 breast carcinoma tissue core images in which the assessors individually and blinded outlined regions of interest and gave their HER2 score 0/1+/2+/3+ to the specific tumor region. The validation set consisted of 86 core images where the result of the automated image analysis software was correlated to the scores provided by the 5 assessors. HER2 fluorescence in situ hybridization (FISH) was performed on all cores and used as a reference standard. The overall agreement between the image analysis software and the digital scorings of the 5 assessors was 92.1% (Cohen’s Kappa: 0.859) in the training set and 92.3% (Cohen’s Kappa: 0.864) in the validation set. The image analysis sensitivity was 99.2% and specificity 100% when correlated to FISH. In conclusion, the Visiopharm HER2 IHC algorithm HER2-CONNECT^TM can discriminate between amplified and non-amplified cases with high accuracy and diminish the equivocal category and thereby provides a promising supplementary diagnostic tool to increase consistency in HER2 assessment.     

Mass screening of breast cancer with imaging diagnosis

Westernization of our life-style and diet has caused a higher incidence of breast cancer in Japan. Although mass screenings such as anamnesis, visual and palpable examinations are provided by local government in Japan, no curable cancer in the early stage can be detected without the use of imaging diagnosis. Furthermore, the image can be saved as a record. Mammography yields images that are best suited for breast cancer examination in terms of sensitivity, specificity and accuracy. However, the large volume of information collected from the images makes diagnosis extremely difficult. In order to ease the burden on the diagnosing physician and to reduce the examination cost, CRT diagnosis by digital images and image selection by an automatic diagnosis supporting system with neuro-computer must replace the present filming method. On the other hand, 100% accuracy can not be achieved by either mammography or ultrasonic examination due to the limitation in depicting images on a display monitor. The accuracy rates of mammography and ultrasonic examination are 91.5% and 87.5% in our hospital. Imaging diagnosis, however, must be efficiently applied in addition to the visual and palpable examinations in promoting mass screening for breast cancer.     

乳腺癌细胞中AIP1/YAP/TAZ的表达及临床意义

目的:通过检测乳腺癌4T1细胞系中AIP1/YAP/TAZ的表达量及敲除AIP1后YAP/TAZ表达量的差异,为乳腺癌寻找新的生物标志物和治疗手段。方法:选取乳腺癌4T1细胞系,通过RT-PCR及Western-Blot检测AIP1/YAP/TAZ的表达量及其差异。结果:AIP1/YAP/TAZ在乳腺癌中均有表达,且敲除AIP1后YAP表达量明显减少（P<0.05）,TAZ表达量也减少。结论:AIP1/YAP/TAZ可作为一种潜在的生物标志物来预测乳腺癌的恶性程度,为探索乳腺癌的治疗提供新的方向。     

乳腺癌中survivin表达的预后价值

目的：研究凋亡抑制基因survivin在乳腺癌中表达的预后价值。方法：采用免疫组化SP法检测180例乳腺癌石蜡标本中survivin表达情况,并对survivin表达与乳腺癌的临床分期、雌激素受体表达、月经状况、腋淋巴结转移、病理类型、无病生存时间以及总生存时间的关系进行了分析。结果：Survivin在乳腺癌中的阳性表达率为66.1%,survivin的表达与乳腺癌的临床分期、雌激素受体、月经状况、腋淋巴结是否转移及病理类型无关（P〉0.05）;单因素分析结果表明survivin表达与乳腺癌病人的无病生存时间和总生存时间显著相关,survivin表达阳性病人的无病生存时间和总生存时间均显著低于survivin表达阴性的病人;多因素Cox回归分析结果表明survivin的表达状况是决定乳腺癌病人无病生存时间的独立因素,而与总生存时间无关。结论：Survivin是判断乳腺癌预后的一个独立生物学指标,阳性表达病人的预后较阴性表达病人差。