Digital breast pathology: validation and training for primary digital practice

Digital pathology is a technology which is transforming the way in which breast histopathology specimens are assessed, reported and reviewed. Large scale clinical laboratory deployments of whole slide imaging systems are occurring in diagnostic pathology departments across the world, requiring laboratory and diagnostic staff to navigate new skills and workflows. Transferring from conventional light microscopy assessment of breast specimens to the use of whole slide images (WSI) can be a challenging experience. This article describes an approach to training and validation for breast consultant histopathologists, which has been used and adapted at a number of sites. Examples of types of case that are suitable for training, and some of the potential “pitfalls” of digital reporting for the novice are described, and practical advice regarding clinical digital breast workflow is shared.     

基于糖酵解途径的乳腺癌治疗研究进展*

细胞所需的能量主要由葡萄糖的氧化供应，乳腺癌细胞的葡萄糖氧化途径与正常的乳腺细胞有较大差异，这种差异集中表现在乳腺癌细胞糖酵解显著增强，并以此作为供能的主要途径，是乳腺癌向恶性进展的重要特征之一。造成癌细胞糖酵解效应增强的主要原因是细胞中糖酵解酶及糖酵解途径调节因子活性的增强，通过对这些酶及调节因子的活性靶向抑制，可以抑制癌细胞糖酵解的进行，促使癌细胞死亡。本文主要综述近些年以糖酵解途径调节因子和关键酶为靶点的乳腺癌治疗研究进展。      

乳腺浸润性小叶癌的临床病理特征、诊疗现状及展望

乳腺癌是目前全球范围内发病率最高的恶性肿瘤，且组织学类型多样。乳腺浸润性小叶癌（ILC）是第二大常见浸润性乳腺癌组织学亚型（占5%~15%），近三十年来其发病率有所升高。E-钙黏蛋白表达缺失是乳腺ILC最主要的分子特征，可导致细胞间缺乏黏附性、肿瘤呈特殊弥漫性浸润生长，这给临床查体及影像学检查带来了一定挑战。尽管多数乳腺ILC患者激素受体呈阳性表达、对内分泌治疗反应良好，但也存在内分泌治疗耐药问题。此外，近年研究证实乳腺ILC患者预后并非如既往研究报道的那样良好，仅基于肿瘤分期及分子分型的治疗原则似乎并不完全适用于乳腺ILC，可能有必要将其作为独立的临床实体行进一步研究。本文主要综述了乳腺ILC的流行病学及临床特征、病理学及分子特征、诊断、治疗、预后、未来治疗方向等，以供临床医师更好地了解并优化乳腺ILC的临床诊断和个体化治疗参考。     

Low-Grade and High-Grade Invasive Ductal Carcinomas of the Breast Follow Divergent routes of Progression

Low-grade invasive ductal carcinoma is almost diploid,and has frequent losses of chromosome 16q,which is shared by other precancerous lesions of the mammary gland such as flat epithelial atypia(FEA),atypical ductal hyperplasia(ADH),and lownuclear grade ductal carcinoma in situ(DCIS).The genetic alterations accumulate in a stepwise fashion as the precancerous lesions progress to invasve ductal carcinoma.This supports the linear progression model of breast cancer from FEA,through ADH,to lownuclear grade DCIS as non-obligate early events in low-grade IDC evolution.In contrast,high-grade carcinoma tends to aneuploidy with complex genetic alterations-most importantly,frequent gains at chromosome 16q.Frequent losses at chromosome 16q in lowgrade IDC and gains in the same arm of the same chromosome in high-grade IDC imply that these lesions are two end outcomes of different disease processes and that they do not lie in the same continuum of a process.Therefore,low-grade and high-grade IDC are two distinct diseases with a divergent route of progression.     

Hypomethylation of DNA-binding inhibitor 4 serves as a potential biomarker in distinguishing acquired tamoxifen-refractory breast cancer

Objective: To explore the methylation status of DNA-binding inhibitor 4 (ID4) in tamoxifen-refractory (TR) breast cancer. Methods: From January 2012 to December 2014, breast cancer patients managed by radical mastectomy previously and receiving tamoxifen treatment for at least 12 months were enrolled. According to the response to tamoxifen, patients were divided into TR group and tamoxifen-sensitive (TS) group. Genomic DNA was isolated from fasting venous blood, and methylight technique was applied to determine the methylation status of ID4. Results: 43 patients with TS breast cancer and 31 patients with TR breast cancer were enrolled. No significant difference between groups was observed in term of patients’ characteristics, such as age (P=0.693), progesterone receptor (P=0.970), menopausal status (P=0.784) and histological type (P=0.537), while the stage of cancer in TR group was significantly higher than TS group (P<0.001). Compared to TS group, PMR of ID4 was significantly higher in TR group (P=0.002). ROC curve analysis indicated that ID4 yielded an AUC of 0.716 with 77.4% sensitivity and 62.79% specificity in distinguishing TR breast cancer at the cut point of 3.8%. The PMR cut point of ID4 was set at 6.8% in survival analysis, log-rank test indicated the risk of disease progression was comparable between patients with ID4 hypermethylation or hypomethylation (P=0.287). Conclusion: ID4 hypomethylation is present in TR breast cancer, and it may serve as a potential biomarker in distinguishing TR breast cancer. However, the results need further validation in larger studies.     

Comparative prognostic value of low-density lipoprotein cholesterol and C-reactive protein in patients with stable coronary artery disease treated with percutaneous coronary intervention and chronic statin therapy

BackgroundThe comparative prognostic value of low density lipoprotein-cholesterol (LDL-C) and C-reactive protein (CRP) in patients with stable coronary artery disease (CAD) treated with percutaneous coronary intervention (PCI) and statin therapy is poorly investigated.MethodsThe study included 7595 patients with stable CAD treated with PCI. Based on a cut-off of 100 mg/dl for LDL-C and 3 mg/L for CRP, patients were divided into 4 groups: patients with LDL-C ≤ 100 mg/dl and CRP ≤ 3 mg/L (n = 2795); patients with LDL-C > 100 mg/dl and CRP ≤ 3 mg/L (n = 2091); patients with LDL-C ≤ 100 mg/dl and CRP > 3 mg/L (n = 1296); and patients with LDL-C > 100 mg/dl and CRP > 3 mg/L (n = 1413). Statins at discharge were prescribed in all patients. The primary outcome was 1-year all-cause mortality.ResultsOne-year mortality was 2.1% (160 deaths): 1.2% (33 deaths) among patients with LDL-C ≤ 100 mg/dl and CRP ≤ 3 mg/L, 1.4% (28 deaths) among patients with LDL-C > 100 mg/dl and CRP ≤ 3 mg/L, 4.8% (60 deaths) among patients with LDL-C ≤ 100 mg/dl and CRP > 3 mg/L and 2.9% (39 deaths) among patients with LDL-C > 100 mg/dl and CRP > 3 mg/L (P < 0.001). After adjustment, CRP (hazard ratio [HR] = 1.64, 95% confidence interval [CI] 1.33–2.02, for 1 standard deviation increase in the logarithmic scale) but not LDL-C (HR = 1.03 [0.90–1.17], for 30 mg/dl increase) showed an independent association with 1-year mortality. CRP (P = 0.045) but not LDL-C (P = 0.294) increased the discriminatory power of multivariable model for prediction of mortality.ConclusionIn patients with stable CAD treated with PCI and statin therapy, CRP but not LDL-C was independently associated with increased risk of 1-year mortality.     

ARK5 is associated with the invasive and metastatic potential of human breast cancer cells

Purpose  

To investigate the effects of Akt/ARK5 pathways on the metastatic potential of human breast cancer cells.     

三阴性乳腺癌靶向治疗研究进展

三阴性乳腺癌（TNBC）作为乳腺癌一种预后较差的亚型,在出现化疗药物抵抗的情况下,由于缺少其他有效治疗方法,疾病往往易快速复发转移。因此针对TNBC新治疗靶点及靶向药物的研究已成为目前国内外研究热点。本文主要针对目前TNBC靶向治疗研究进展进行总结分析,主要包括ADP合同聚合酶抑制剂、抗血管生成靶向药物、抗表皮生长因子受体信号通路靶向药物、雄激素受体拮抗剂、免疫检查点抑制剂、PI3K-AKT-mTOR通路抑制剂等,以期从中找出最有可能成为未来发展方向的靶向治疗方法。