三维超声汇聚征诊断乳腺癌

目的 探讨乳腺三维超声冠状面成像显示汇聚征诊断乳腺癌的价值。方法 观察128例乳腺肿瘤患者(共132个病灶)的三维超声汇聚征和二维超声毛刺征显示情况,与病理结果对照,比较二者对乳腺癌的诊断价值,分析汇聚征显示率与肿瘤大小之间的关系。结果 132个乳腺肿块中,76个为乳腺癌,56个为乳腺良性病变,汇聚征和毛刺征诊断乳腺癌的敏感度、特异度、准确率、阳性预测值和阴性预测值分别为63.16%(48/76)、92.86%(52/56)、75.76%(100/132)、92.31%(48/52)、65.00%(52/80)和44.74%(34/76)、91.07%(51/56)、64.39%(85/132)、87.18%(34/39)、54.84%(51/93)。汇聚征对于诊断乳腺癌的敏感度明显高于毛刺征(P<0.05)。汇聚征的显示率随着乳腺肿块直径增加而逐渐降低(P<0.01)。结论 乳腺超声实时三维成像显示汇聚征对于乳腺癌的诊断价值高于二维超声显示毛刺征。汇聚征对于诊断乳腺癌具有较高特异度,对小乳癌有较高敏感度,对于早期乳腺癌的诊断和鉴别诊断具有重要价值。     

Whole-Breast Ultrasound for Breast Screening and Archiving

The incidence of breast cancer is increasing worldwide, reinforcing the importance of breast screening. Conventional hand-held ultrasound (HHUS) for breast screening is efficient and relatively easy to perform; however, it lacks systematic recording and localization. This study investigated an electromagnetic tracking-based whole-breast ultrasound (WBUS) system to facilitate the use of HHUS for breast screening. One-hundred nine breast masses were collected, and the detection of suspicious breast lesions was compared between the WBUS system, HHUS and a commercial automated breast ultrasound (ABUS) system. The positioning error between WBUS and ABUS (1.39 ± 0.68 cm) was significantly smaller than that between HHUS and ABUS (1.62 ± 0.91 cm, p = 0.014) and HHUS and WBUS (1.63 ± 0.9 cm, p = 0.024). WBUS is a practical clinical tool for breast screening that can be used instead of the often unavailable and costly ABUS.     

Conventional US and 2-D Shear Wave Elastography of Virtual Touch Tissue Imaging Quantification: Correlation with Immunohistochemical Subtypes of Breast Cancer

Our study aimed to investigate the correlation of the imaging features obtained using conventional ultrasound (US) and elastography (conventional strain elastography of elasticity imaging [EI], virtual touch tissue imaging [VTI] and 2-D shear wave elastography [2-D-SWE] of virtual touch tissue imaging quantification [VTIQ]) with the clinicopathologic features and immunohistochemical (IHC) subtypes of breast cancer. The sample consisted of images from 202 patients with 206 breast lesions that were confirmed as breast cancers. Lesions with HER2 overexpression (luminal B HER2+ or HER2+) had higher mean shear wave velocity (SWV) values than the others. Older patients, lower histologic grade, no lymphovascular invasion and no lymph node metastasis were associated with luminal A (p < 0.001). There were significant differences in SWV values, histologic grade and lymph node status among the different pathologic types. This association may allow the use of 2-D-SWE in the pre-operative prediction of tumor characteristics and biologic activity, which may determine the prognosis in a non-invasive manner.     

Metabolic Tumor Burden Assessed by Dual Time Point [<Superscript>18</Superscript>F]FDG PET/CT in Locally Advanced Breast Cancer: Relation with Tumor Biology

Purpose

The aim of the study was to investigate the influence of dual time point 2-deoxy-2-[¹⁸F]fluoro-D-glucose ([¹⁸F]FDG) positron emission tomography/x-ray computed tomography (PET/CT) on the standard uptake value (SUV) and volume-based metabolic variables of breast lesions and their relation with biological characteristics and molecular phenotypes.

Procedures

Retrospective analysis including 67 patients with locally advanced breast cancer (LABC). All patients underwent a dual time point [¹⁸F]FDG PET/CT, 1 h (PET-1) and 3 h (PET-2) after [¹⁸F]FDG administration. Tumors were segmented following a three-dimensional methodology. Semiquantitative metabolic variables (SUV_max, SUV_mean, and SUV_peak) and volume-based variables (metabolic tumor volume, MTV, and total lesion glycolysis, TLG) were obtained. Biologic prognostic parameters, such as the hormone receptors status, p53, HER2 expression, proliferation rate (Ki-67), and grading were obtained. Molecular phenotypes and risk-classification [low: luminal A, intermediate: luminal B HER2 (?) or luminal B HER2 (+), and high: HER2 pure or triple negative] were established. Relations between clinical and biological variables with the metabolic parameters were studied. The relevance of each metabolic variable in the prediction of phenotype risk was assessed using a multivariate analysis.

Results

SUV-based variables and TLG obtained in the PET-1 and PET-2 showed high and significant correlations between them. MTV and SUV variables (SUV_max, SUV_mean, and SUV_peak) where only marginally correlated. Significant differences were found between mean SUV variables and TLG obtained in PET-1 and PET-2. High and significant associations were found between metabolic variables obtained in PET-1 and their homonymous in PET-2. Based on that, only relations of PET-1 variables with biological tumor characteristics were explored. SUV variables showed associations with hormone receptors status (p < 0.001 and p = 0.001 for estrogen and progesterone receptor, respectively) and risk-classification according to phenotype (SUV_max, p = 0.003; SUV_mean, p = 0.004; SUV_peak, p = 0.003). As to volume-based variables, only TLG showed association with hormone receptors status (estrogen, p < 0.001; progesterone, p = 0.031), risk-classification (p = 0.007), and grade (p = 0.036). Hormone receptor negative tumors, high-grade tumors, and high-risk phenotypes showed higher TLG values. No association was found between the metabolic variables and Ki-67, HER2, or p53 expression.

Conclusion

Statistical differences were found between mean SUV-based variables and TLG obtained in the dual time point PET/CT. Most of PET-derived parameters showed high association with molecular factors of breast cancer. However, dual time point PET/CT did not offer any added value to the single PET acquisition with respect to the relations with biological variables, based on PET-1 SUV, and volume-based variables were predictors of those obtained in PET-2.

     

Magnetomotive Optical Coherence Tomography for the Assessment of Atherosclerotic Lesions Using αvβ3 Integrin-Targeted Microspheres

Purpose

We investigated the early-stage fatty streaks/plaques detection using magnetomotive optical coherence tomography (MM-OCT) in conjunction with α_vβ₃ integrin-targeted magnetic microspheres (MSs). The targeting of functionalized MSs was investigated by perfusing ex vivo aortas from an atherosclerotic rabbit model in a custom-designed flow chamber at physiologically relevant pulsatile flow rates and pressures.

Procedures

Aortas were extracted and placed in a flow chamber. Magnetic MS contrast agents were perfused through the aortas and MM-OCT, fluorescence confocal, and bright field microscopy were performed on the ex vivo aorta specimens for localizing the MSs.

Results

The results showed a statistically significant and stronger MM-OCT signal (3.30?±?1.73 dB) from the aorta segment perfused with targeted MSs, compared with the nontargeted MSs (1.18?±?0.94 dB) and control (0.78?±?0.41 dB) aortas. In addition, there was a good co-registration of MM-OCT signals with confocal microscopy.

Conclusions

Early-stage fatty streaks/plaques have been successfully detected using MM-OCT in conjunction with α_vβ₃ integrin-targeted magnetic MSs.     

乳腺癌DBT征象与不同分子亚型之间的相关性

目的探讨乳腺癌数字乳腺断层摄影(DBT)征象与不同分子亚型相关性。方法回顾性分析经病理证实的260例乳腺癌患者的资料。采用单因素和多因素Logistic回归分析,以评估乳腺癌DBT征象与其分子亚型的关联。结果Luminal A、B型多表现为不规则的毛刺状肿块,毛刺与Luminal A型(OR 3.77,P<0.001)关系密切;肿块边缘清楚、形态规则高度提示三阴型(OR 12.53,P<0.001);HER-2型(OR 2.42,P=0.015)、Luminal B型(OR 1.69,P=0.047)与微钙化相关,其中单纯钙化多见于HER-2型(P=0.005),肿块伴钙化多见于Luminal B型(P=0.017);不同亚型间钙化形态有统计学差异(P=0.027),Luminal A型(12,52.2%)多表现为无定形钙化,HER-2型(10,55.6%)多表现为细小多形性钙化。结论乳腺癌某些DBT征象可用于预测特定的亚型,并帮助指导临床治疗策略。     

PS1-05: Disparities in Breast Cancer Survival by Molecular Subtype and Race/Ethnicity

Background/Aims Little information exists on breast cancer survival rates according to molecular profiles among different race/ethnic groups. We investigated the impact of molecular subtypes on breast cancer-specific survival by race/ethnicity in a large group of medically-insured women diagnosed with breast cancer. Methods The cohort included 20,749 diverse Kaiser Permanente Southern California (KPSC) women diagnosed with breast cancer (AJCC Stage 0-IV) between 1996 and 2007, and followed through 2009. The women's cancers were classified into four main molecular subtypes: luminal A (ER+ and/or PR+/HER2-); luminal B (ER+ and/or PR+/HER2+); basal-like ("triple negative", ER-/PR-/HER2-); and HER2+/ER-. The outcome was breast cancer mortality. Follow-up began on the date of surgery and ended on date of death, health plan disenrollment, or study's end. Hazard rate ratios (HR) and 95% confidence intervals (CI) were estimated using Cox proportional hazards models. We adjusted for age, tumor characteristics, cancer treatments, income, and comorbidity. Results Of the 20,749 women, 65% were white non-Hispanic (n=13,487); 13% Black (n=2,697); 12% Hispanic (n=2,490); and 10% Asian (n=2,075). We observed 2,019 deaths (10%) deaths due to breast cancer over 14 years of follow-up. In all race/ethnic groups combined, breast cancer mortality was higher in women with basal-like (HR 2.90, 2.38-3.53) and HER2+/ER- (HR 1.98, 1.55-2.54) tumors compared to women with luminal A subtype (referent group). In addition, we examined breast cancer mortality in each molecular subtype, stratified by race/ethnic group. Among women with luminal A tumors, Black women were more likely to die of breast cancer (HR 1.53, 1.02-2.29) than white women (referent group). In women with luminal B tumors, South Asians had a 10-fold increase in breast cancer mortality (HR=10.57, 1.42-78.64) compared to whites; however, numbers were small and the confidence interval was wide. Among women with basal-like tumors, Black women had a greater mortality risk (HR 1.36, 1.02-1.82) compared to white women. In women with HER2+/ER- tumors, breast cancer mortality was similar across the race/ethnic groups. No other comparisons were significant. Discussion Despite similar access to healthcare, we found survival disparities by race/ethnic groups within the luminal A, luminal B, and basal-like molecular subtypes of breast cancer.     

Deformable mapping using biomechanical models to relate corresponding lesions in digital breast tomosynthesis and automated breast ultrasound images

This work investigates the application of a deformable localization/mapping method to register lesions between the digital breast tomosynthesis (DBT) craniocaudal (CC) and mediolateral oblique (MLO) views and automated breast ultrasound (ABUS) images. This method was initially validated using compressible breast phantoms. This methodology was applied to 7 patient data sets containing 9 lesions. The automated deformable mapping algorithm uses finite element modeling and analysis to determine corresponding lesions based on the distance between their centers of mass (d_COM) in the deformed DBT model and the reference ABUS model. This technique shows that location information based on external fiducial markers is helpful in the improvement of registration results. However, use of external markers are not required for deformable registration results described by this methodology. For DBT (CC view) mapped to ABUS, the mean d_COM was 14.9 ± 6.8 mm based on 9 lesions using 6 markers in deformable analysis. For DBT (MLO view) mapped to ABUS, the mean d_COM was 13.7 ± 6.8 mm based on 8 lesions using 6 markers in analysis. Both DBT views registered to ABUS lesions showed statistically significant improvements (p ≤ 0.05) in registration using the deformable technique in comparison to a rigid registration. Application of this methodology could help improve a radiologist's characterization and accuracy in relating corresponding lesions between DBT and ABUS image datasets, especially for cases of high breast densities and multiple masses.     

Correlation between Ultrasound Appearance of Small Breast Cancer and Axillary Lymph Node Metastasis

To study the correlation of ultrasonographic signs of small breast cancer (maximum diameter ≤2.0?cm) with axillary lymph node metastasis, pre-operative ultrasonographic images of 153 small breast malignant neoplasms in 143 breast cancer patients were analyzed according to their pathologic features. Of the small breast tumors included, 47 showed axillary lymph node metastasis. Diagnosis of all patients was obtained with radical axillary surgery or a sentinel lymph node biopsy procedure. Ultrasonographic signs included irregular shape, microlobulated contour, spiculation, microcalcification, posterior echo attenuation, blood-flow grade, perforating vessels, changes in fascia or cooper's ligament and maximum cortical thickness of lymph nodes. The relationship between ultrasonographic features and axillary lymph node metastasis was analyzed using a chi-square test for univariate distributions and logistic regression for multivariate analysis. A logistic regression model was established by taking the pathologic diagnosis of lymph node metastasis as the dependent variable and the ultrasonographic signs of each small breast cancer as independent variables. In small breast cancer, characteristics such as perforating vessels and maximum cortical thickness of lymph nodes >3.0?mm correlated well with axillary lymph node metastasis as determined by univariate analysis (χ²?=?13.945, 51.276, respectively, p?<0.05) and multivariate analysis (OR?=?48.783, 46.754, respectively, p?<0.05).     

影响乳腺癌穿刺活检与术后病理分子分型差异的自动乳腺全容积成像特征

目的探讨影响乳腺癌粗针穿刺活检与术后病理分子分型差异的自动乳腺全容积成像（ABVS）特征。 方法回顾性分析2014年11月至2020年10月东部战区总医院收治的63例乳腺癌患者,共63个病灶。所有患者行改良根治术前均行粗针穿刺活检及ABVS检查。比较术前粗针穿刺活检与术后标本分子分型存在差异组（有差异组）与二者病理结果一致组（无差异组）ABVS特征的差异,并采用Logistic回归分析手术前后分子分型差异的独立影响因素。 结果手术病理结果显示,Luminal A型15个（23.8%）,Luminal B型39个（61.9%）,HER-2过表达型6个（9.5%）,三阴型3个（4.8%）。其中14个病灶的粗针穿刺活检与术后分子分型之间存在差异。有差异组（n=14）与无差异组（n=49）的肿块最大径、边界、形态、边缘及汇聚征比较,差异具有统计学意义（P均＜0.05）。Logistic回归分析结果表明,伴有汇聚征（OR=0.113,95%CI：0.015~0.865）、形态不规则（OR=0.117,95%CI：0.015~0.912）、边界模糊（OR=0.171,95%CI：0.029~0.992）以及边缘有毛刺（OR=12.576,95%CI：1.783~88.717）是粗针穿刺活检与术后分子分型差异的独立影响因素（P均＜0.05）。 结论ABVS在一定程度能够指导粗针穿刺活检,减少穿刺活检病理与术后病理分子分型的差异,提高穿刺诊断准确性,为临床医师提供可靠的诊断依据和参考信息。     

Systematic analysis on the relationship between luminal enhancement, convolution kernel, plaque density, and luminal diameter of coronary artery stenosis: a CT phantom study

To systematically investigate into the relationships between luminal enhancement, convolution kernel, plaque density, and stenosis severity in coronary computed tomography (CT) angiography. A coronary phantom including 63 stenoses (stenosis severity, 10–90 %; plaque densities, ?100 to 1,000 HU) was loaded with increasing solutions of contrast material (luminal enhancement, 0–700 HU) and scanned in an anthropomorphic chest. CT data was acquired with prospective triggering using 64-section dual-source CT; reconstructions were performed with soft-tissue (B26f) and sharp convolution kernels (B46f). Two blinded and independent readers quantitatively assessed luminal diameter and CT number of plaque using electronic calipers. Measurement bias between phantom dimensions and CT measurements were calculated. Multivariate linear regression models identified predictors of bias. Inter- and intra-reader agreements of luminal diameter and CT number measurements were excellent (ICCs > 0.91, p < 0.01, each). Measurement bias of luminal diameter and plaque density was significantly (p < 0.01, each) lower (?12 % and 58 HU, respectively) with B46f as opposed to B26f, especially in plaque densities >200 HU. Measurement bias was significantly (p < 0.01, each) correlated (ρ = 0.37–55 and ρ = ?0.70–85) with the differences between luminal enhancement and plaque density. In multivariate models, bias of luminal diameter assessment with CT was correlated with plaque density (β = 0.09, p < 0.05). Convolution kernel (β = ?0.29 and ?0.38), stenosis severity (β = ?0.45 and ?0.38), and luminal enhancement (β = ?0.11 and ?0.29) represented independent (p < 0.05,each) predictors of measurement bias of luminal diameter and plaque number, respectively. Significant independent relationships exist between luminal enhancement, convolution kernel, plaque density, and luminal diameter, which have to be taken into account when performing, evaluating, and interpreting coronary CT angiography.     

ABUS examination time: An observational study of operators’ experience

ObjectiveIn this study we aimed to evaluate the operation times of ABUS by technologists during the learning time course and share the learning experience.Materials and methodThe first consequent 400 examinations after the installation of an ABUS unit in the breast clinic between August 2017 and December 2017 were included. Total examination time was measured for each procedure. The initial and final examination times during the learning period were compared. Data were analyzed with the Mann-Whitney Test.ResultsThe acquisition times for routine six position examination ranged between eight and 36 minutes with an average of 13.2 ± 3.58 min. The examination time for the eight position examination ranged between 18 and 32 min, with an average of 22.9 ± 3.93 min. The overall average examination time was 13.3 ± 3.98 min. There was a significant difference (p = 0.00) between the average initial and final examination times of the learning period with an average decrease of 10.6 min.ConclusionThe average time of an ABUS examination for an average breast is less than 15 min. ABUS examination time reduced as technologists became familiar with the sonographic anatomy of the breast and experienced in positioning technique during the learning curve.     

Computer-aided diagnosis for the classification of breast masses in automated whole breast ultrasound images

New automated whole breast ultrasound (ABUS) machines have recently been developed and the ultrasound (US) volume dataset of the whole breast can be acquired in a standard manner. The purpose of this study was to develop a novel computer-aided diagnosis system for classification of breast masses in ABUS images. One hundred forty-seven cases (76 benign and 71 malignant breast masses) were obtained by a commercially available ABUS system. Because the distance of neighboring slices in ABUS images is fixed and small, these continuous slices were used for reconstruction as three-dimensional (3-D) US images. The 3-D tumor contour was segmented using the level-set segmentation method. Then, the 3-D features, including the texture, shape and ellipsoid fitting were extracted based on the segmented 3-D tumor contour to classify benign and malignant tumors based on the logistic regression model. The Student’s t test, Mann-Whitney U test and receiver operating characteristic (ROC) curve analysis were used for statistical analysis. From the Az values of ROC curves, the shape features (0.9138) are better than the texture features (0.8603) and the ellipsoid fitting features (0.8496) for classification. The difference was significant between shape and ellipsoid fitting features (p = 0.0382). However, combination of ellipsoid fitting features and shape features can achieve a best performance with accuracy of 85.0% (125/147), sensitivity of 84.5% (60/71), specificity of 85.5% (65/76) and the area under the ROC curve Az of 0.9466. The results showed that ABUS images could be used for computer-aided feature extraction and classification of breast tumors. (E-mail: rfchang@csie.ntu.edu.tw)     

不同分子分型乳腺癌新辅助化疗后缓解率的差异性研究

目的 探讨新辅助化疗对不同分子分型乳腺癌的疗效.方法 选取本院2007年6月-2014年6月本院收治的122例乳腺癌患者,明确其肿瘤分期,免疫组织化学技术明确ER、PR、HER2及Ki-67表达状况,并分为腺腔A型（Luminal A）、腺腔B型（LuminalB）、HER2型、基底细胞型（Basal-like）,采用阿霉素联合多西紫杉醇类方案（ET方案）对所有患者进行2周期的新辅助化疗,判断肿瘤治疗效果及患者毒副反应发生情况.结果 新辅助化疗后总有效人数为40例,占总人数的32.79％,其中Lurninal A型总有效率为9.10％ （3/33）,Luminal B型总有效率为12.9％（4/31）,HER2型总有效率为53.8％（14/26）,Basal-like型总有效率为59.4％（19/32）.腺腔A型与腺腔B型的总有效率差异无统计学意义（P＞0.05）,HER2型与基底细胞型总有效率差异无统计学意义（P＞0.05）,而HER2型与基底细胞型的总有效率均高于腺腔A型与腺腔B型,差异有统计学意义（P＜0.05）.不同分子分型乳腺癌患者化疗中均出现不同程度的化疗副反应,未出现导致化疗中断的副反应.结论 不同分子分型的乳腺癌患者采用ET方案新辅助化疗的疗效不同,乳腺癌分子分型可能是乳腺癌治疗具有价值的依据之一,较Luminal而言,HER2型与Basal-like型患者的总有效率更高.     

US-Guided Optical Tomography: Correlation with Clinicopathologic Variables in Breast Cancer

We tested the relat1ionships between total hemoglobin concentration (THC), as measured with ultrasound (US)-guided optical tomography, and clinicopathologic variables in invasive ductal cancers; and we evaluated the clinical significance of THC. Fifty-three patients with 65 invasive ductal carcinomas underwent US-guided biopsy and were scanned with a hand-held probe consisting of a co-registered US transducer and an NIR (near-infrared) imager. The lesion location provided by co-registered US was used to guide optical imaging. Light absorption was measured at two optical wavelengths. From this measurement, tumor angiogenesis was assessed on the basis of calculated THC. We investigated the relationships between maximum THC and clinicopathologic variables (tumor size [≤2 cm or >2 cm], metastasis to lymph node or distant organ, histologic grade, lymphovascular invasion, status of ER, PR, HER2 and Ki-67, and triple negativity). The mean maximum THC in the breast cancers was 223.3 ± 106.3 μmol/L. In univariate analysis, HER2 positivity, tumor size, and Ki-67 positivity showed significant correlations with maximum THC (p < 0.05). In multivariate analysis including tumor size, and ER, PR, HER2, and Ki-67 status, HER2 positivity correlated with maximum THC significantly (p = 0.007, parameter estimate 76.44). Maximum THC correlated with HER2, Ki-67 and tumor size in this group of ductal breast carcinomas. Thus, US-guided diffuse optical tomography (US-DOT) may potentially be used to predict tumor aggressiveness in patients with invasive breast cancers.     

Patient satisfaction with service quality as a predictor of survival outcomes in breast cancer

Purpose

Despite the recognized relevance of symptom burden in breast cancer, there has been limited exploration of whether an individual patient's assessment of the overall quality of care received might influence outcome. We therefore evaluated the relationship between patient-reported satisfaction with service quality and survival in breast cancer.

Methods

A random sample of 1,521 breast cancer patients treated at Cancer Treatment Centers of America. A questionnaire which covered several dimensions of patient satisfaction was administered. Items were measured on a seven-point Likert scale ranging from “completely dissatisfied” to “completely satisfied”. Univariate and multivariate Cox regression was used to evaluate the association between patient satisfaction and survival.

Results

Of 1,521 patients, 836 were newly diagnosed, and 685 had previously been treated. A number of 409, 611, 323, and 178 patients had stage I, II, III, and IV disease, respectively. A total of 1,106 (72.7 %) patients were completely satisfied with the overall service quality, while 415 (27.3 %) were not. On univariate analysis, completely satisfied patients had a significantly lower risk of mortality compared to those not completely satisfied (HR?=?0.62; 95 % CI 0.50–0.76; p?<?0.001). On multivariate analysis, completely satisfied patients demonstrated significantly lower mortality (HR?=?0.71; 95 % CI 0.57–0.87; p?=?0.001) compared to those not completely satisfied.

Conclusions

Patient satisfaction with service quality was an independent predictor of survival in breast cancer. Further exploration of a possible meaningful relationship between patient satisfaction with the care they receive and outcomes in breast cancer is indicated.     

HER2‐Positive Endometrial Cancer Subtype Carries Poor Prognosis

Endometrial cancer (EC) is a hormone‐dependent, most frequent malignancy of the female genital tract, yet no molecular subtype classification based receptor status (estrogen receptor [ER], progesterone receptor [PR], human epidermal growth factor receptor 2 [HER2]) has been established so far. Assuming that molecular subtypes might differ fundamentally in EC, we analyzed expression levels of ER, PR, and HER2 with immunohistochemistry and aimed to determine clinical significance of four molecular subtypes: ER+/PR+/HER2+; ER+/PR+/HER2−, ER−/PR−/HER2+, and ER−/PR−/HER2−. The study included 400 formalin‐fixed paraffin‐embedded primary tumor EC samples which covered all stages of endometrial carcinoma, from IA to IVB. ER−/PR−/HER2+ subtype correlated with the poorest outcome, ER+/PR+/HER2− subtype was associated with the most favorable prognosis (p = 0.002). Molecular subtype division remained an independent prognostic factor in multivariate analysis, accompanying parameters such as diabetes, hypertension, stage, myometrial infiltration, and metastases, all of which yielded hazard ratios between 1.39 and 2.23. ER+/PR+/HER2+ and ER+/PR+/HER2− subtypes had low average TP53 and TOP2A expression levels when compared with ER−/PR−/HER2+ and ER−/PR−/HER2− (both p < 0.00001). Molecular subtypes in EC do show diversity in terms of prognosis, clinicopathological, and molecular characteristics. ER−/PR−/HER2+ subtype exhibit is exceptionally aggressive tumor characteristics. Subtype differentiation might aid prediction of treatment response in EC.     

Fluorine-18 Labeling of the HER2-Targeting Single-Domain Antibody 2Rs15d Using a Residualizing Label and Preclinical Evaluation

Purpose

Our previous studies with F-18-labeled anti-HER2 single-domain antibodies (sdAbs) utilized 5F7, which binds to the same epitope on HER2 as trastuzumab, complicating its use for positron emission tomography (PET) imaging of patients undergoing trastuzumab therapy. On the other hand, sdAb 2Rs15d binds to a different epitope on HER2 and thus might be a preferable vector for imaging in these patients. The aim of this study was to evaluate the tumor targeting of F-18 -labeled 2Rs15d in HER2-expressing breast carcinoma cells and xenografts.

Procedures

sdAb 2Rs15d was labeled with the residualizing labels N-succinimidyl 3-((4-(4-[¹⁸F]fluorobutyl)-1H-1,2,3-triazol-1-yl)methyl)-5-(guanidinomethyl)benzoate ([¹⁸F]RL-I) and N-succinimidyl 4-guanidinomethyl-3-[¹²⁵I]iodobenzoate ([¹²⁵I]SGMIB), and the purity and HER2-specific binding affinity and immunoreactivity were assessed after labeling. The biodistribution of I-125- and F-18-labeled 2Rs15d was determined in SCID mice bearing subcutaneous BT474M1 xenografts. MicroPET/x-ray computed tomograph (CT) imaging of [¹⁸F]RL-I-2Rs15d was performed in this model and compared to that of nonspecific sdAb [¹⁸F]RL-I-R3B23. MicroPET/CT imaging was also done in an intracranial HER2-positive breast cancer brain metastasis model after administration of 2Rs15d-, 5F7-, and R3B23-[¹⁸F]RL-I conjugates.

Results

[¹⁸F]RL-I was conjugated to 2Rs15d in 40.8 ± 9.1 % yield and with a radiochemical purity of 97–100 %. Its immunoreactive fraction (IRF) and affinity for HER2-specific binding were 79.2 ± 5.4 % and 7.1 ± 0.4 nM, respectively. [¹²⁵I]SGMIB was conjugated to 2Rs15d in 58.4 ± 8.2 % yield and with a radiochemical purity of 95–99 %; its IRF and affinity for HER2-specific binding were 79.0 ± 12.9 % and 4.5 ± 0.8 nM, respectively. Internalized radioactivity in BT474M1 cells in vitro for [¹⁸F]RL-I-2Rs15d was 43.7 ± 3.6, 36.5 ± 2.6, and 21.7 ± 1.2 % of initially bound radioactivity at 1, 2, and 4 h, respectively, and was similar to that seen for [¹²⁵I]SGMIB-2Rs15d. Uptake of [¹⁸F]RL-I-2Rs15d in subcutaneous xenografts was 16–20 %ID/g over 1–3 h. Subcutaneous tumor could be clearly delineated by microPET/CT imaging with [¹⁸F]RL-I-2Rs15d but not with [¹⁸F]RL-I-R3B23. Intracranial breast cancer brain metastases could be visualized after intravenous administration of both [¹⁸F]RL-I-2Rs15d and [¹⁸F]RL-I-5F7.

Conclusions

Although radiolabeled 2Rs15d conjugates exhibited lower tumor cell retention both in vitro and in vivo than that observed previously for 5F7, given that it binds to a different epitope on HER2 from those targeted by the clinically utilized HER2-targeted therapeutic antibodies trastuzumab and pertuzumab, F-18-labeled 2Rs15d has potential for assessing HER2 status by PET imaging after trastuzumab and/or pertuzumab therapy.

     

Comparative Study of Automated Breast 3-D Ultrasound and Handheld B-Mode Ultrasound for Differentiation of Benign and Malignant Breast Masses

The automated breast volume scanner (ABVS) represents a new technology for diagnosing breast masses. In this study, a total of 219 breast masses in 175 patients underwent both conventional handheld B-mode ultrasound (HHUS) and ABVS examinations, and the differences in the diagnostic values of the two modalities for benign and malignant breast masses were compared with the final pathologic findings. In addition, the diagnostic accuracy for breast masses with features including retraction phenomenon and hyperechoic rim in the coronal plane of the ABVS was evaluated. There were no differences between the ABVS and HHUS in terms of sensitivity (92.5% vs. 88.0%), specificity (86.2% vs. 87.5%), accuracy (88.1% vs. 87.2%), false-positive rate (13.8% vs. 12.5%), false-negative rate (11.8% vs. 7.5%), positive predictive value (74.7% vs. 75.6%) and negative predictive value (96.3% vs. 94.3%) (p > 0.05 for all). However, there were significant differences between the malignant and benign masses with respect to retraction phenomenon and hyperechoic rim in the coronal plane of the ABVS. For retraction phenomenon, both the specificity and positive predictive value of a malignant diagnosis reached 100%, and the accuracy and false-positive rate were 96.8% and 0, respectively; for the hyperechoic rim, the specificity, negative predictive value and accuracy of a benign diagnosis were 92.8%, 95.3% and 95.9%, respectively. Overall, ABVS is a promising modality for the clinical diagnosis of breast masses with retraction phenomenon and hyperechoic rim in the coronal plane, although the ABVS and HHUS do not differ in diagnostic accuracy for the differentiation of malignant or benign breast masses.     

Association of exercise capacity and the heart rate profile during exercise stress testing with subclinical coronary atherosclerosis: data from the Heinz Nixdorf Recall study

Background

Exercise capacity and heart rate profile parameters obtained from exercise stress testing as well as the subclinical coronary atherosclerosis burden from cardiac CT have been suggested to improve cardiovascular (CV) risk stratification beyond traditional risk factors (RF) in persons at risk of CV events.

Aim

To study the association of exercise stress-test variables with the coronary artery calcium (CAC) burden in relation to age, sex and traditional RF in subjects without known coronary artery disease from the general population.

Methods

In 3,163 subjects, CV and RF were measured, a bicycle stress test was performed and the electron beam CT-based CAC-Agatston score was quantified.

Results

Exercise capacity, chronotropic response and an abnormal HR recovery were significantly and inversely related to CAC scores in men and women in univariate unadjusted analysis. This association was diminished after adjustment for age and sex and further after adjustment for traditional risk factors. In multivariate analysis, chronotropic response in men [estimate (95% CI): 0.94 (0.91–0.97), P = 0.0005] and an abnormal HR recovery (<15 bpm after 1 min) in women [estimate: 1.34 (1.07–1.70), P = 0.013] but not exercise capacity remained associated with CAC independent of traditional RF. In subjects not taking lipid-lowering, antiarrhythmic or antihypertensive drugs, estimates for the observed associations were essentially unchanged. The clinical ability of these variables to predict a high CAC score was limited.

Conclusion

The strong inverse association of exercise capacity, chronotropic response and abnormal HR recovery during exercise stress testing with the CAC burden in unadjusted univariate analysis is largely influenced by age, sex and cardiovascular RFs. The degree, to which exercise stress-test variables and the CAC burden independently contribute to the prediction of cardiovascular events, remains to be shown.