Efficiency of a Preoperative Axillary Ultrasound and Fine-Needle Aspiration Cytology to Detect Patients with Extensive Axillary Lymph Node Involvement

Background

Recent studies have demonstrated that axillary lymph node dissection (ALND) does not affect patient survival, even in those with one or two positive sentinel lymph nodes (SLNs). On the other hand, patients with 3 or more metastatic lymph nodes are eligible for chemotherapy. Therefore, it is crucial to identify a priori patients at risk of having a high number of metastatic axillary lymph nodes for their surgical and/or clinical management. Ultrasound (US) guided Fine-Needle Aspiration (FNA) has been proven to be a useful and highly specific method for detecting metastatic axillary lymph nodes. However, only one recent study has evaluated the efficiency of this method in identifying patients with high metastatic nodal involvement. Our aim was to validate US-guided FNA as a reliable method to discriminate a priori patients with >3 metastatic lymph nodes.

Methods

A retrospective series of 1287 breast cancer patients who underwent a simultaneous preoperative breast and axillary US to stage their axilla was collected. A total of 365 patients, with either positive SLNs (278) or positive axillary lymph nodes detected via US-guided FNA (87), underwent ALND. In these two subgroups, we compared the number of metastatic lymph nodes in the axilla.

Results

The number of metastatic axillary lymph nodes in patients who underwent US-guided FNA was significantly higher (63% had >3 metastatic lymph nodes) than that in patients with SLNs positive for micro- or macrometastases (3% and 27%, respectively) (P<0.001, χ ² = 117.897).

Conclusions

Preoperative axillary US-guided FNA could act as a reliable tool in identifying breast cancer patients with extensive nodal involvement.     

Imaging Lymphatic System in Breast Cancer Patients with Magnetic Resonance Lymphangiography

Objective

To investigate the feasibility of gadolinium (Gd) contrast-enhanced magnetic resonance lymphangiography (MRL) in breast cancer patients within a typical clinical setting, and to establish a Gd-MRL protocol and identify potential MRL biomarkers for differentiating metastatic from non-metastatic lymph nodes.

Materials and Methods

32 patients with unilateral breast cancer were enrolled and divided into 4 groups of 8 patients. Groups I, II, and III received 1.0, 0.5, and 0.3 ml of intradermal contrast; group IV received two 0.5 ml doses of intradermal contrast. MRL images were acquired on a 3.0 T system and evaluated independently by two radiologists for the number and size of enhancing lymph nodes, lymph node contrast uptake kinetics, lymph vessel size, and contrast enhancement patterns within lymph nodes.

Results

Group III patients had a statistically significant decrease in the total number of enhancing axillary lymph nodes and lymphatic vessels compared to all other groups. While group IV patients had a statistically significant faster time to reach the maximum peak enhancement over group I and II (by 3 minutes), there was no other statistically significant difference between imaging results between groups I, II, and IV. 27 out of 128 lymphatic vessels (21%) showed dilatation, and all patients with dilated lymphatic vessels were pathologically proven to have metastases. Using the pattern of enhancement defects as the sole criterion for identifying metastatic lymph nodes during Gd-MRL interpretation, and using histopathology as the gold standard, the sensitivity and specificity were estimated to be 86% and 95%, respectively.

Conclusion

Gd-MRL can adequately depict the lymphatic system, can define sentinel lymph nodes, and has the potential to differentiate between metastatic and non-metastatic lymph nodes in breast cancer patients.     

Magnetic Resonance Imaging Diagnosis of Metastatic Lymph Nodes in a Rabbit Model: Efficacy of PJY10, a New Ultrasmall Superparamagnetic Iron Oxide Agent,with Monodisperse Iron Oxide Core and Multiple-Interaction Ligands

Background

Accurate diagnosis of lymph node metastasis is crucial in treatment planning for cancer patients. Despite the use of various parameters, making correct diagnosis of a small metastatic or a hyperplastic benign node is still a challenge. In this study, we evaluated the feasibility of detecting lymph node metastasis using a new ultrasmall superparamagnetic iron oxide particle, PJY10, in a rabbit model.

Methods

To make metastatic and benign lymph nodes, either VX2 carcinoma or fecal material suspension was inoculated into thighs of 56 rabbits three weeks or three days before magnetic resonance (MR) imaging, respectively. T2*-weighted 3T MR imaging was performed before and 24 hours after PJY10 injection (5.2 [n = 15], 7.8 [n = 17], and 10.4 [n = 24] mg Fe/kg). MR images were correlated with pathologic results to calculate sensitivity and specificity. Quantitative analysis of the signal intensity (SI) – number of voxels_[low] (the fraction of the number of voxels with the normalized SI on the postcontrast image lower than that on the precontrast image) and mean SI ratio – was also performed for each lymph node.

Results

Sensitivities were 100% at all three dosages, whereas specificity increased with increasing dosage (89% at 10.4 mg Fe/kg). The benign nodes had a significantly higher number of voxels_[low] and a lower mean SI ratio than the metastatic nodes at the dosage of 10.4 mg Fe/kg (P<.001). Az values were 0.905 for the number of voxels_[low] and 0.952 for the mean SI ratio. The number of voxels_[low] (P = .019) and the mean SI ratio (P = .034) had significant correlations with the histopathologic area ratio of metastatic foci in the metastatic nodes at 10.4 mg Fe/kg.

Conclusions

PJY10 enabled clear demonstration of lymph node metastasis with high sensitivity and specificity at its optimal dosage of 10.4 mg Fe/kg.     

PRC2/EED-EZH2 Complex Is Up-Regulated in Breast Cancer Lymph Node Metastasis Compared to Primary Tumor and Correlates with Tumor Proliferation In Situ

Background

Lymph node metastasis is a key event in the progression of breast cancer. Therefore it is important to understand the underlying mechanisms which facilitate regional lymph node metastatic progression.

Methodology/Principal Findings

We performed gene expression profiling of purified tumor cells from human breast tumor and lymph node metastasis. By microarray network analysis, we found an increased expression of polycomb repression complex 2 (PRC2) core subunits EED and EZH2 in lymph node metastatic tumor cells over primary tumor cells which were validated through real-time PCR. Additionally, immunohistochemical (IHC) staining and quantitative image analysis of whole tissue sections showed a significant increase of EZH2 expressing tumor cells in lymph nodes over paired primary breast tumors, which strongly correlated with tumor cell proliferation in situ. We further explored the mechanisms of PRC2 gene up-regulation in metastatic tumor cells and found up-regulation of E2F genes, MYC targets and down-regulation of tumor suppressor gene E-cadherin targets in lymph node metastasis through GSEA analyses. Using IHC, the expression of potential EZH2 target, E-cadherin was examined in paired primary/lymph node samples and was found to be significantly decreased in lymph node metastases over paired primary tumors.

Conclusions/Significance

This study identified an over expression of the epigenetic silencing complex PRC2/EED-EZH2 in breast cancer lymph node metastasis as compared to primary tumor and its positive association with tumor cell proliferation in situ. Concurrently, PRC2 target protein E-cadherin was significant decreased in lymph node metastases, suggesting PRC2 promotes epithelial mesenchymal transition (EMT) in lymph node metastatic process through repression of E-cadherin. These results indicate that epigenetic regulation mediated by PRC2 proteins may provide additional advantage for the outgrowth of metastatic tumor cells in lymph nodes. This opens up epigenetic drug development possibilities for the treatment and prevention of lymph node metastasis in breast cancer.     

Quantitative,Architectural Analysis of Immune Cell Subsets in Tumor-Draining Lymph Nodes from Breast Cancer Patients and Healthy Lymph Nodes

Background

To date, pathological examination of specimens remains largely qualitative. Quantitative measures of tissue spatial features are generally not captured. To gain additional mechanistic and prognostic insights, a need for quantitative architectural analysis arises in studying immune cell-cancer interactions within the tumor microenvironment and tumor-draining lymph nodes (TDLNs).

Methodology/Principal Findings

We present a novel, quantitative image analysis approach incorporating 1) multi-color tissue staining, 2) high-resolution, automated whole-section imaging, 3) custom image analysis software that identifies cell types and locations, and 4) spatial statistical analysis. As a proof of concept, we applied this approach to study the architectural patterns of T and B cells within tumor-draining lymph nodes from breast cancer patients versus healthy lymph nodes. We found that the spatial grouping patterns of T and B cells differed between healthy and breast cancer lymph nodes, and this could be attributed to the lack of B cell localization in the extrafollicular region of the TDLNs.

Conclusions/Significance

Our integrative approach has made quantitative analysis of complex visual data possible. Our results highlight spatial alterations of immune cells within lymph nodes from breast cancer patients as an independent variable from numerical changes. This opens up new areas of investigations in research and medicine. Future application of this approach will lead to a better understanding of immune changes in the tumor microenvironment and TDLNs, and how they affect clinical outcomes.     

Fine-Needle Aspirates CYFRA 21-1 is a Useful Tumor Marker for Detecting Axillary Lymph Node Metastasis in Breast Cancer Patients

Introduction

To assess whether the value of CYFRA21-1 in the aspirates of ultrasonography-guided fine-needle aspiration biopsy (US-FNAB) can contribute to improving the performances of US-FNAB in the diagnosis of axillary lymph node (LN) metastasis in breast cancer patients.

Methods

US-FNAB was performed in 156 axillary LNs in 152 breast cancer patients (mean age: 51.4 years, range: 17–92 years). Concentrations of CYFRA21-1 were measured from washouts of the syringe used during US-FNAB. Tumor marker concentrations, US-FNAB, intraoperative sentinel node biopsy (SNB), and surgical pathology results were reviewed and analyzed. For comparison, the values of CEA and CA15-3 were also measured from washouts.

Results

Among the 156 LNs, 75 (48.1%) were benign, and 81 (51.9%) were metastases. Mean concentrations of CYFRA21-1 were significantly higher in metastasis compared to benign LNs (P<0.001). US-FNAB combined to CYFRA21-1 showed significantly higher sensitivity, NPV, and accuracy compared to US-FNAB alone (all values P<0.05). All diagnostic indices of US-FNAB combined to CYFRA21-1 were significantly higher compared to US-FNAB combined with CEA or CA15-3 (all P<0.001). Of the 28 metastatic LNs which showed metastasis on SNB, CYFRA21-1 showed higher positive rate of 75.0% (CEA or CA15-3∶60.7%, P = 0.076).

Conclusion

Measuring CYFRA 21-1 concentrations from US-FNAB aspirates improves sensitivity, NPV, and accuracy of US-FNAB alone, and may contribute to reducing up to 75.0% of unnecessary intraoperative SNB. Compared to CEA or CA15-3, CYFRA21-1 shows significantly higher performances when combined to US-FNAB in the preoperative diagnosis of LN metastasis in breast cancer patients.     

Postmastectomy Radiotherapy Improves Disease-Free Survival of High Risk of Locoregional Recurrence Breast Cancer Patients with T1-2 and 1 to 3 Positive Nodes

Objectives

The indications for post-mastectomy radiotherapy (PMRT) with T1-2 breast cancer and 1-3 positive axillary lymph nodes is still controversial. The purpose of this study was to investigate the role of PMRT in T1-2 breast cancer with 1-3 positive axillary lymph node.

Methods

We retrospectively reviewed the file records of 79 patients receiving PMRT and not receiving PMRT (618 patients).

Results

The median follow-up was 65 months. Multivariate analysis showed that PMRT was an independent prognostic factor of locoregional recurrence-free survival (LRFS) (P = 0.010). Subgroup analysis of patients who did not undergo PMRT showed that pT stage, number of positive axillary lymph nodes, and molecular subtype were independent prognostic factors of LRFS. PMRT improved LRFS in the entire group (P = 0.005), but did not affect distant metastasis-free survival (DMFS) (P = 0.494), disease-free survival (DFS) (P = 0.215), and overall survival (OS) (P = 0.645). For patients without PMRT, the 5-year LRFS of low-risk patients (0–1 risk factor for locoregional recurrence) of 94.5% was significantly higher than that of high-risk patients (2-3 risk factors for locoregional recurrence) (80.9%, P < 0.001). PMRT improved LRFS (P = 0.001) and DFS (P = 0.027) in high-risk patients, but did not improve LRFS, DMFS, DFS, and OS in low-risk patients.

Conclusions

PMRT is beneficial in patients with high risk of locoregional recurrence breast cancer patients with T1-2 and 1 to 3 positive nodes.     

Breast cancer in young women in southern Tunisia: Anatomical study and clinical prognostic factors: About a series of 83 patients

Purpose

To define epidemiological, clinical, therapeutic and prognostic factors influencing survival of breast cancer in young women younger than 35 in southern Tunisia.

Material and methods

This is a retrospective study of 83 patients younger than 35 years and treated within tumors mammary committee of Sfax.

Results

The mean age was 31.7 years. T2 stage, high grade with positive node tumors were frequent. Breast surgery was performed for 73 patients. Chemotherapy was neo-adjuvant, adjuvant and palliative for respectively 10, 62 and 13 patients. Radiotherapy was delivered for 65 patients with curative intent and for 8 metastatic patients. Endocrine therapy was adjuvant in 38 patients and palliative in 6 cases. The overall survival (OS) at 5 years was 66.8%. Pejorative prognostic factors in uni-variate analysis were clinical T stage (T3, T4), and the number of involved lymph nodes.

Conclusion

Despite adequate treatment, the prognosis of breast cancer in young women remains worse. Early diagnosis is necessary to promote outcome.     

Association between Lymph Node Ratio and Disease Specific Survival in Breast Cancer Patients with One or Two Positive Lymph Nodes Stratified by Different Local Treatment Modalities

Purpose

Results of the American College of Surgeons Oncology Group (ACOSOG) Z0011 trial indicated that complete axillary node dissection (ALND) may not be warranted in some breast cancer patients with low tumor burden who are undergoing breast-conserving surgery following whole-breast irradiation. However, this study did not address patients undergoing mastectomy or those undergoing breast-conserving surgery without whole-breast radiotherapy. Given that lymph node ratio (LNR; ratio of positive lymph nodes to the total number removed) has been shown to be a prognostic factor in breast cancer, we first sought to determine the prognostic value of LNR in a low risk population comparable to that of the Z0011 trial and further to investigate whether the prognostic significance differs with local treatment modality.

Method

We used the Surveillance Epidemiology and End Results (SEER) database to identify breast cancer patients with T1-T2 tumor and 1–2 positive nodes. Patients were subclassified by the local therapy they underwent for the primary tumor. The prognostic value of LNR in predicting disease-specific survival (DSS) was examined in each treatment group.

Results

A total of 53,109 patients were included. In the subgroup of 20,602 patients who underwent lumpectomy following radiotherapy, LNR was not found to be significantly associated with DSS in both the univariate and multivariate model. For the 4,664 patients treated with mastectomy following radiotherapy, 6,811 treated with lumpectomy without radiotherapy and 21,031 with mastectomy without radiotherapy, LNR independently predict DSS in each of these subgroups.

Conclusions

Our results add evidence to the concept that axillary dissection could be omitted in patients with one or two positive nodes following breast-conserving surgery and whole breast radiation.     

Ratio of Metastatic to Examined Lymph Nodes,a Helpful Staging System and Independent Prognostic Factor of Esophagogastric Junction Cancer

Background

The incidence of the esophagogastric junction cancer is growing rapidly. The purpose of this study is to clarify the outcome of the ratio between metastatic and examined lymph nodes in esophagogastric junction cancer patients with or without 7 examined lymph nodes.

Methods

A total of 3,481 patients who underwent operation are identified from the Surveillance, Epidemiology, and End Results database. Different lymph nodes resected groups are analyzed to test the lymph nodes ratio factor.

Results

There are 2522 patients with 7 or more lymph nodes resected and 959 patients with less than 7 lymph nodes resected. Lymph nodes ratio and lymph node involvement are independent prognostic factors. But the lymph nodes ratio categories have a better prognostic value than the lymph node involvement categories. Compared with lymph node involvement categories, lymph nodes ratio categories represent patients with more homogeneous overall survival rate.

Conclusions

This study defines that the lymph nodes ratio is an independent prognostic factor for esophagogastric junction cancer. The lymph nodes ratio can prevent stage migration and may be a helpful system to predict the prognosis of esophagogastric junction cancer patients.     

Preoperative Axillary Staging with 3.0-T Breast MRI: Clinical Value of Diffusion Imaging and Apparent Diffusion Coefficient

The axillary staging in newly diagnosed breast cancer is under major evolution. The aims of this study were to define the diagnostic performance of 3.0-T diffusion-weighted imaging (DWI) in the detection of axillary metastases in newly diagnosed breast cancer, to assess apparent diffusion coefficients (ADCs) for histopathologically confirmed metastatic lymph nodes in a clinical setting. Altogether 52 consecutive breast cancer patients underwent magnetic resonance imaging and DWI in addition to axillary ultrasound. ADCs of axillary lymph nodes were analysed by two breast radiologists and ultrasound-guided core biopsies were taken. In a separate reading by one radiologist two types of region of interests were used for a smaller group of patients. Altogether 56 axillae (121 lymph nodes) were included in the statistical analysis. Metastatic axillae (51.8%) had significantly lower ADCs (p<0.001). Mean ADCs were 0.663–0.676 x 10^-3 mm²/s for the histologically confirmed metastatic LNs and 1.100–1.225 x 10^-3 mm²/s for the benign. The sensitivity, specificity, and accuracy of DWI were 72.4%, 79.6%, and 75.9%, respectively with threshold ADC 0.812 x 10^-3 mm²/s. Region of interest with information on the minimum value increased the diagnostic performance (area under the curve 0.794 vs. 0.619). Even though ADCs are significantly associated with histopathologically confirmed axillary metastases the diagnostic performance of axillary DWI remains moderate and ultrasound-guided core biopsies or sentinel lymph node biopsies cannot be omitted.     

超声弹性成像技术对腋窝淋巴结性质的诊断价值

目的:研究超声成像技术对腋窝淋巴结性质的诊断价值。方法:从2013年5月至2014年2月,选择我院50例乳腺癌患者,对所有患者进行弹性成像技术检测出74个腋窝淋巴结。对所有腋窝淋巴结使用四分法进行评分,将其与手术病理结果进行比较。结果:74个腋窝淋巴结中,反应性淋巴结有42个,纵径为(0.9-2.4)cm,平均纵径为(1.31±0.33)cm;乳腺癌腋窝淋巴结转移个数为25个,纵径为(1.2±3.8)cm,平均纵径为(2.04±0.72)cm。良性淋巴结弹性评分大多为1分(54.55%)以及2分(27.27%),恶性淋巴结评分多为3分(63.33%)以及4分(20.00%)。恶性淋巴结评分为(3.12±0.61)分,良性淋巴结评分为(1.68±0.74)分,结果显示,两组淋巴结弹性评分具有较大差异(即P<0.05),具有可比性。结论:综上所述,超声弹性成像技术操作较为简便,效果较为直观,评分法能够提供组织的硬度信息,在临床工作中,与常规超声联合应用有利于提高评价腋窝淋巴结良恶性性质的准确度。值得临床推荐使用。     

Diagnostic value of intraoperative histopathological examination of the sentinel nodes in breast cancer and skin melanoma—Preliminary results of single centre retrospective study

Objective

Intraoperative histopatological examination of the sentinel nodes enables selection of patients who need dissection of the regional lymphatic system during the same operation. The aim of this study is to evaluate the diagnostic value of intraoperative histopathological examination of the sentinel nodes in breast cancer and skin melanoma. Intraoperative histopathology of the sentinel nodes as a diagnostic method is used in patients with melanoma and breast cancer. Recent studies have proved it to be an effective method for evaluating the nodes in the final histopathology. Intraoperative histopathological examination of the sentinel nodes is not performed routinely and there is no clear position on this issue. In this paper we try to prove that intraoperative test gives patients the simultaneous benefits of removal of regional lymph nodes metastases and earlier initiation of adjuvant therapy.

Methods

The study comprises 137 patients with breast cancer and 35 patients with malignant skin melanoma. Sentinel nodes were intraoperatively sectioned and examined by means of the imprint method and frozen section evaluation. The patients with positive sentinel nodes underwent immediate dissection of regional lymph nodes. Those with negative sentinel nodes diagnosed in the intraoperative examination, but positive in final pathologic results, underwent subsequent dissection of regional lymph nodes.

Results

60 sentinel lymph nodes were found in 35 patients with skin melanoma. In 3 patients, 3 sentinel lymph nodes were false negative in the intraoperative histopathological examination. No false positive sentinel lymph nodes were found. 249 sentinel lymph nodes were found in the intraoperative histopathological examination in 137 patients with breast cancer. There were no false positive sentinel nodes, but there were 7 false negative sentinel nodes. In this study, only 5 (3.6%) patients with breast cancer and 3 (8.5%) patients with skin melanoma required another regional operation.

Conclusion

The method of intraoperative histopathological evaluation of the sentinel nodes enables identification of metastases in these lymph nodes and gives a possibility to carry out a one-step regional lymphadenectomy and start the adjuvant therapy earlier.     

Can the Tumor Deposits Be Counted as Metastatic Lymph Nodes in the UICC TNM Staging System for Colorectal Cancer?

Objective

The 7th edition of AJCC staging manual implicitly states that only T1 and T2 lesions that lack regional lymph node metastasis but have tumor deposit(s) will be classified in addition as N1c, though it is not consistent in that pN1c is also an option for pT3/T4a tumors in the staging table. Nevertheless, in this TNM classification, how to classify tumor deposits (TDs) in colorectal cancer patients with lymph node metastasis (LNM) and TDs simultaneously is still not clear. The aim of this study is to investigate the possibility of counting TDs as metastatic lymph nodes in TNM classification and to indentify its prognostic value for colorectal cancer patients.

Methods and Results

In this retrospective study, 513 cases of colorectal cancer with LNM were reviewed. We proposed a novel pN (npN) category in which TDs were counted as metastatic lymph nodes in the TNM classification. Cancer-specific survival according to the npN or pN category was analyzed using Kaplan-Meier survival curves. Univariate and multivariate analyses were performed to indentify significant prognostic factors. Harrell''s C statistic was used to test the predictive capacity of the prognostic models. The results revealed that the TD was a significant prognostic factor in colorectal cancer. Univariate and multivariate analyses uniformly indicated that the npN category was significantly correlated with prognosis. The results of Harrell''s C statistical analysis demonstrated that the npN category exhibited a superior predictive capacity compared to the pN category of the 7th edition TNM classification. Moreover, we also found no significant prognostic differences in patients with or without TD in the same npN categories.

Conclusions

The counting of TDs as metastatic lymph nodes in the TNM classification system is potentially superior to the classification in the 7th edition of the TNM staging system to assess prognosis and survival for colorectal cancer patients.     

The Added Diagnostic Value of Dynamic Contrast-Enhanced MRI at 3.0 T in Nonpalpable Breast Lesions

Objective

To investigate the added diagnostic value of 3.0 Tesla breast MRI over conventional breast imaging in the diagnosis of in situ and invasive breast cancer and to explore the role of routine versus expert reading.

Materials and Methods

We evaluated MRI scans of patients with nonpalpable BI-RADS 3–5 lesions who underwent dynamic contrast-enhanced 3.0 Tesla breast MRI. Initially, MRI scans were read by radiologists in a routine clinical setting. All histologically confirmed index lesions were re-evaluated by two dedicated breast radiologists. Sensitivity and specificity for the three MRI readings were determined, and the diagnostic value of breast MRI in addition to conventional imaging was assessed. Interobserver reliability between the three readings was evaluated.

Results

MRI examinations of 207 patients were analyzed. Seventy-eight of 207 (37.7%) patients had a malignant lesion, of which 33 (42.3%) patients had pure DCIS and 45 (57.7%) invasive breast cancer. Sensitivity of breast MRI was 66.7% during routine, and 89.3% and 94.7% during expert reading. Specificity was 77.5% in the routine setting, and 61.0% and 33.3% during expert reading. In the routine setting, MRI provided additional diagnostic information over clinical information and conventional imaging, as the Area Under the ROC Curve increased from 0.76 to 0.81. Expert MRI reading was associated with a stronger improvement of the AUC to 0.87. Interobserver reliability between the three MRI readings was fair and moderate.

Conclusions

3.0 T breast MRI of nonpalpable breast lesions is of added diagnostic value for the diagnosis of in situ and invasive breast cancer.     

高频彩色多普勒超声对乳腺癌腋窝淋巴结性质的鉴别价值

目的:研究高频彩色多普勒超声对乳腺癌腋窝良性淋巴结与腋窝转移性淋巴结的鉴别价值。方法:选择2015年2月~2016年6月在我院进行诊治的乳腺癌患者150例,应用高频二维超声结合彩色多普勒血流显像技术,观察腋窝肿大淋巴结的声像图及血流情况。结果:经二维超声发现,乳腺癌腋窝良性淋巴结的皮质多向心增厚(68.93%)、长短径比L/S多2.0(70.58%)、多不融合(93.14%)、多无钙化斑(97.06%);腋窝转移性淋巴结的皮质多偏心增厚(68.48%)、长短径比L/S多2.0(69.57%)、多融合(68.48%)、多有钙化斑(77.17%);两者相比有明显差异(P0.05);经彩色多普勒血流显像技术发现,乳腺癌腋窝良性淋巴结的血流信号分布多呈门型(63.17%),血流丰富程度多为Ⅱ级(54.35%);腋窝转移性淋巴结的血流信号分布多呈周边型(68.93%),血流丰富程度多为Ⅲ级(72.83%);两者相比有明显差异(P0.05)。结论:乳腺癌腋窝良性淋巴结与腋窝转移性淋巴结在内部回声、形态、血流分布特点等方面有显著的差异,高频彩色多普勒超声对乳腺癌腋窝良性淋巴结与腋窝转移性淋巴结具有较高的鉴别价值。     

The molecular subtype classification is a determinant of sentinel node positivity in early breast carcinoma

Introduction

Several authors have underscored a strong relation between the molecular subtypes and the axillary status of breast cancer patients. The aim of our work was to decipher the interaction between this classification and the probability of a positive sentinel node biopsy.

Materials and Methods

Our dataset consisted of a total number of 2654 early-stage breast cancer patients. Patients treated at first by conservative breast surgery plus sentinel node biopsies were selected. A multivariate logistic regression model was trained and validated. Interaction covariate between ER and HER2 markers was a forced input of this model. The performance of the multivariate model in the training and the two validation sets was analyzed in terms of discrimination and calibration. Probability of axillary metastasis was detailed for each molecular subtype.

Results

The interaction covariate between ER and HER2 status was a stronger predictor (p = 0.0031) of positive sentinel node biopsy than the ER status by itself (p = 0.016). A multivariate model to determine the probability of sentinel node positivity was defined with the following variables; tumour size, lympho-vascular invasion, molecular subtypes and age at diagnosis. This model showed similar results in terms of discrimination (AUC = 0.72/0.73/0.72) and calibration (HL p = 0.28/0.05/0.11) in the training and validation sets. The interaction between molecular subtypes, tumour size and sentinel nodes status was approximated.

Discussion

We showed that biologically-driven analyses are able to build new models with higher performance in terms of breast cancer axillary status prediction. The molecular subtype classification strongly interacts with the axillary and distant metastasis process.     

The Association between Leptin Level and Breast Cancer: A Meta-Analysis

Background

Contradictory results have been reported regarding the association between leptin level and breast cancer. Therefore, a meta-analysis was performed to investigate this issue.

Methods

Published literature from PubMed and the Chinese National Knowledge Infrastructure (CNKI) Database was retrieved. This study was performed based on different cases and control groups. The combined effect () with 95% confidence interval (CI) was calculated using fixed-effects or random-effects model analysis.

Results

Overall, the mean serum leptin level of case groups was significantly higher than that of control groups. A) For 9 studies comparing breast cancer cases and healthy controls the combined effect was 0.58 with 95% CI (0.48, 0.68). B) For 4 studies comparing premenopausal breast cancer cases and healthy controls the was 0.32 (0.12, 0.52). C) For 5 studies comparing postmenopausal cases and healthy controls the was 0.65 (0.46, 0.84). D) For 4 studies comparing breast cancer cases and breast benign controls the was 0.38 (0.17, 0.59). E) For 2 studies comparing premenopausal breast cancer cases and breast benign controls the was 0.33 (-0.25, 0.91). F) For 6 studies comparing postmenopausal breast cancer cases and breast benign controls the was 0.39 (0.19, 0.60). G) For 4 studies comparing lymph node metastasis positive cases and negative controls the was 0.72 (0.45, 1.00). H) For 3 studies comparing breast benign cases and healthy controls the was 0.71 (0.41, 1.01).

Conclusion

This meta-analysis suggests that leptin level plays a role in breast cancer and has potential for development as a diagnostic tool.     

CD1d-expressing breast cancer cells modulate NKT cell-mediated antitumor immunity in a murine model of breast cancer metastasis

Background

Tumor tolerance and immune suppression remain formidable obstacles to the efficacy of immunotherapies that harness the immune system to eradicate breast cancer. A novel syngeneic mouse model of breast cancer metastasis was developed in our lab to investigate mechanisms of immune regulation of breast cancer. Comparative analysis of low-metastatic vs. highly metastatic tumor cells isolated from these mice revealed several important genetic alterations related to immune control of cancer, including a significant downregulation of cd1d1 in the highly metastatic tumor cells. The cd1d1 gene in mice encodes the MHC class I-like molecule CD1d, which presents glycolipid antigens to a specialized subset of T cells known as natural killer T (NKT) cells. We hypothesize that breast cancer cells, through downregulation of CD1d and subsequent evasion of NKT-mediated antitumor immunity, gain increased potential for metastatic tumor progression.

Methodology/Principal Findings

In this study, we demonstrate in a mouse model of breast cancer metastasis that tumor downregulation of CD1d inhibits iNKT-mediated antitumor immunity and promotes metastatic breast cancer progression in a CD1d-dependent manner in vitro and in vivo. Using NKT-deficient transgenic mouse models, we demonstrate important differences between type I and type II NKT cells in their ability to regulate antitumor immunity of CD1d-expressing breast tumors.

Conclusions/Significance

The results of this study emphasize the importance of determining the CD1d expression status of the tumor when tailoring NKT-based immunotherapies for the prevention and treatment of metastatic breast cancer.