乳腺癌精准医疗大数据的可视化分析

目的分析乳腺癌精准医疗的既往概况以及动态演化历程,探索未来乳腺癌的精准医疗研究的前沿热点和发展趋势。方法①以中国万方数据库和美国的Web of Science核心数据库关于乳腺癌精准医疗相关文献为信息来源,可视化分析相关文献的发表年份、国家、机构、作者、期刊、基金以及关键词分布,同时比较不同分子分型以及不同靶点乳腺癌研究的文献分布差异;②检索中国临床试验注册中心、北美临床试验注册中心、中国国家药品监督管理局以及美国食品药品监督管理局乳腺癌精准医疗的临床注册以及药物信息。结果①在中国共有450篇与乳腺癌精准医疗有关的研究文章,而在国际上有2303篇与乳腺癌精准治疗有关的研究文章,在中国以及全球均于2016年出现有关乳腺癌精准治疗研究文章的爆发式增长;Luminal A型、Luminal B型、HER2过表达型、基底细胞型(Basal-like型)以及三阴性乳腺癌中以三阴性乳腺癌精准医疗的研究文章数量最多,而乳腺癌精准治疗的主要靶点为HER2,EGFR,CDK4/6,PIK3CA和PARP,其中文献量最大的为HER2;②在全球范围内,美国的哈佛大学是发表乳腺癌精准治疗最多的机构,其次为法国国家健康与医学研究院,而后是加州大学以及德克萨斯大学,而中国发文机构的排名还不太高,仍有很大前进的空间;③美国是乳腺癌精准治疗研究的主要国家,发表超过900篇研究;④中国发文量最多的研究作者为解放军总医院第五医学中心(原解放军第307医院)乳腺肿瘤科的江泽飞教授,而在全球范围内发文量最多的是ANDRE F(巴黎第十一大学)和KATOH M(日本国立癌症研究中心);⑤《中华乳腺病杂志(电子版)》是中国发表乳腺癌精准治疗研究文章最多的期刊,全球发表乳腺癌精准治疗文章的主要期刊为《Personalized Medicine》;⑥全球范围中发表乳腺癌精准治疗研究文章的最主要资助机构为美国卫生与公共服务部以及美国国立卫生研究院,其次为美国国家癌症研究所和中国国家自然科学基金委员会;⑦中国临床注册中心收录的最新乳腺癌研究有177项,而北美临床注册中心收录的最新乳腺癌研究达3663项,主要集中在美国、欧洲和中国;⑧目前已上市的乳腺癌精准治疗药物的治疗靶点主要为HER2,也存在靶点为PARP-1,2,3、PIK3CA、PD-L1、mTOR、CDK4/6、EGFR、HER4的药物,研发机构主要为诺华、辉瑞等跨国药企。结论建立全国甚至全球性精准乳腺癌信息服务集成整合平台将有助于推动乳腺癌精准医疗的发展,同时有助于提升中国企业乳腺癌精准治疗药物的研发能力。     

精准医疗时代早期乳腺癌患者外科治疗的热点问题

乳腺癌是女性最常见的恶性肿瘤之一,对于早期乳腺癌患者,外科治疗仍然有其不可替代的作用。在精准医疗的背景下,通过回顾近期早期乳腺癌外科治疗的若干热点问题,对外科治疗策略制定、保乳手术范围、区域淋巴结处理、乳房重建时机抉择及乳腺微创治疗等方面进行综述,以期多学科合作,实施早期乳腺癌精准外科治疗。     

精准医疗—肿瘤诊治的新模式

精准医疗（precision medicine）又称为个性化医疗,是根据个体基因特征、环境以及生活习惯,为病人量身设计出最佳治疗方案,以期达到治疗效果最大化和不良反应最小化的一种定制医疗模式。作为一种全新的医学概念与医疗模式,日益在恶性肿瘤临床治疗中显示出价值。人类基因组计划的完成和测序技术的飞速发展,极大地促进了肿瘤基因组测序研究,发现了大量与肿瘤相关的基因组改变,为肿瘤的个体化精准治疗提供理论和技术支撑。本文主要对精准医疗的概念、实施步骤以及在肿瘤治疗中的应用做一简要的概述。     

瘤内异质性分析指导乳腺癌精准医疗

瘤内异质性与肿瘤的发生、转移和耐药等密切相关,是近年来肿瘤领域研究的热点,也是精准医疗的突破口.很多研究已经证实乳腺癌存在广泛的瘤内异质性,给临床上寻找理想的肿瘤标志物和精准治疗带来了极大的困难.深入解析肿瘤异质性的特征、产生机制以及研究临床可量化肿瘤异质性的方法是肿瘤精准治疗的关键.     

基于文献分析的精准乳腺癌个体化医疗进展研究

目的　根据近5年乳腺癌精准医学和个体化医学相关文献，分析其国内外研究进展，探究个体化医疗的现状和未来的发展方向，构建以患者为中心的乳腺癌个体化医疗方案。方法　抽取万方医学网（限定中国科技核心期刊）和Web of Science 两个数据库中的乳腺癌精准相关文献，对其进行统计分析，从年发文趋势、国家、研究机构、国内外热门研究领域与高频关键词分布等角度入手。结果　共检索到精准医学相关中文文献3 336篇，英文文献20 241篇，近5年乳腺癌在精准医学方面的文献呈总体上升趋势；发文量最大的国家为美国（30.4％），其次是中国（24.0％）；国内高发文机构为中国科学院系统（295 篇／1.415％）；研究热点主要表现为通过液体活检和新一代基因测序实现精确诊断，通过靶向用药、精准外科和免疫治疗实现精确治疗。精准医疗更重视“病”的深度特征和“药”的高度精确性，形成高水平医疗技术。结论　精准医学是实现个体化医学的基础和必须条件。乳腺癌精准医学的研究以实现个体化医学为目标，以基因测序和靶向药物为基础，结合遗传因素、环境因素、药物反应个体差异，并考虑年轻乳腺癌保乳治疗等复杂议题，因此现代个体化医学应当逐渐形成以患者为中心，了解自身基因，针对性改善外部环境，从而形成个体化治疗和用药的医疗模式，进而预防疾病发生，提高生活质量。但是目前的个体化医学仍面临严峻的挑战，需要我们共同的努力。     

三阴性乳腺癌各亚型精准医疗策略研究进展

三阴性乳腺癌(Triple negative breast cancer,TNBC)约占乳腺癌总数的15%,缺乏明确的靶向治疗及内分泌治疗靶点,治疗手段相对单一,且复发较早,总生存率较差。早期TNBC的主要治疗方法是新辅助化疗和确定性手术,TNBC分子分型的提出使得TNBC个体化治疗进入精准治疗时代。基于TNBC各亚型特点进行精准医疗策略,可使患者获得临床获益,本文旨在对TNBC各亚型的精准医疗策略研究进展及精准医疗临床获益进行综述。     

三阴性乳腺癌精准治疗的机遇

三阴性乳腺癌（triple-negative breast cancer ,TNBC）是一类有着极大异质性的疾病,个体间生物学行为差异较大,根据基因表达谱分析,TNBC 细分为生物学行为各异的6 个类别,各类别对不同治疗表现出不同的敏感性。在医疗行业步入精准的时代,寻找TNBC 可治疗的各类靶点对不同类别TNBC 的精准靶向治疗可能具有指导作用。     

乳腺癌运动干预研究进展的可视化分析

目的 分析“乳腺癌运动干预”领域的研究热点及趋势,以期为乳腺癌运动干预方案设置提供理论依据。方法 以Web of Science核心数据库近五年所收录的乳腺癌运动干预类的7 134篇文献为对象,运用CiteSpaceⅤ进行可视化知识图谱分析,生成可视化图谱包括学科分布、国家或地区分布、关键词共现或突显、关键词时间线图谱等进行分析。结果 近年“乳腺癌运动干预”领域得到了快速的发展,学科分布主要集中在心血管系统与心脏病学和肿瘤学等。美国、英格兰和意大利等国家发文量排名靠前。身体质量指数、生活质量中介中心性分别为0.81、0.52,在知识图谱中有着重要的地位。关键突显图谱和时间线图谱显示心脏毒性是该领域的研究热点。结论 乳腺癌运动干预研究热点主要集中在心血管及其相关领域,目前处于高速发展阶段。未来研究方向包括体重控制、生活质量和心脏毒性。     

肺癌精准医疗靶点筛查的现状与趋势

肺癌的发病率和病死率居全球恶性肿瘤的首位,近年来,综合诊疗模式虽然在一定范围内提高了肺癌的整体诊疗水准,但其疗效仍不尽人意。随着科学技术的不断发展,精准医疗模式逐渐应用于临床,进一步掌握参与肿瘤发生、发展过程的信号转导通路及其他生物学途径的精准医疗变的越发重要。新型药物的靶向治疗取得了阶段性进展,显著改变了肺癌的治疗策略。与传统的化学疗法和放射疗法相比,靶向治疗使多数晚期肺癌患者受益,且不良反应更少,明显提高了患者的生活质量。本文将对肺癌的精准医疗模式进行总结,并对未来可能的治疗方向提出设想。     

New diagnostic method for breast cancer based on clinical mammographic data and its clinical validation

Background  

Recently, the numbers of patients with breast cancer have increased rapidly in Japan, and about 40,000 people contract the disease annually today. Therefore, secondary prevention by breast cancer screening has become an important issue. Presently, mammography is used frequently for the diagnosis of breast cancer, but the reading of mammograms is difficult, and physicians must attend training classes specified by the Central Committee on Quality Control of Mammographic Screening and obtain a license to perform screening. Assessment categories are used for the evaluation of mammograms. Although they provide a scale for the diagnosis of breast cancer, the interpretation of mammograms is dependent on the physician’s subjective judgment, and the advent of an objective evaluation method is awaited.     

End points in cancer clinical trials and the drug approval process.

The sequencing of the human genome and the elucidation of many molecular pathways important in cancer cell proliferation, apoptosis, and metastasis have provided unprecedented opportunities for development of new agents to prevent and treat cancer. The types of molecules in development are increasingly varied and include small molecules, monoclonal antibodies, antisense oligonucleotides, and ribozymes. Thus, the variety of anticancer agents in clinical development is now greater than ever before, and the number of agents currently in clinical trial for various cancer indications is estimated to exceed 400. Many of these drugs would be expected to work in only narrowly defined patient populations that must be prospectively identified. Thus, the development of the therapeutic agent must often be linked to the development of a molecular diagnostic product. Drugs that produce primarily cytostatic effects might not be expected to produce regression of tumor masses; thus, evaluation of such agents would best be done in populations of patients with low tumor burdens but high risk of disease progression. As traditional clinical end points prove more difficult to apply in evaluation of molecularly targeted therapies, a great need exists to define and validate surrogate markers of effect and of benefit. New clinical trial designs and end points are necessary to permit more efficient evaluation of putative cancer treatments. This editorial will review commonly used clinical trial end points and describe their potential advantages and disadvantages to expedite the drug approval process required in the United States.     

Adjuvant chemotherapy based on evidence-based medicine for breast cancer patients

Adjuvant chemotherapy for breast cancer patients has been derived from the results of various clinical studies and metaanalysis. Currently, an anthracycline-containing regimen is a standard chemotherapy for node-negative breast cancer patients with any risk of recurrence. Node-positive breast cancer patients employ AC followed by taxane. The concept of dose-dense therapy or adjuvant trastuzumab for HER 2-positive breast cancer patients will be introduced in the near future. We have to catch the procedures of standard treatments and treat our patients with the latest knowledge. Therefore, we can refer to any guidelines based on evidence-based medicine.     

Overdiagnosis and overtreatment of breast cancer: microsimulation modelling estimates based on observed screen and clinical data

There is a delicate balance between the favourable and unfavourable side-effects of screening in general. Overdiagnosis, the detection of breast cancers by screening that would otherwise never have been clinically diagnosed but are now consequently treated, is such an unfavourable side effect. To correctly model the natural history of breast cancer, one has to estimate mean durations of the different pre-clinical phases, transition probabilities to clinical cancer stages, and sensitivity of the applied test based on observed screen and clinical data. The Dutch data clearly show an increase in screen-detected cases in the 50 to 74 year old age group since the introduction of screening, and a decline in incidence around age 80 years. We had estimated that 3% of total incidence would otherwise not have been diagnosed clinically. This magnitude is no reason not to offer screening for women aged 50 to 74 years. The increases in ductal carcinoma in situ (DCIS) are primarily due to mammography screening, but DCIS still remains a relatively small proportion of the total breast cancer problem.     

Overdiagnosis and overtreatment of breast cancer: Microsimulation modelling estimates based on observed screen and clinical data

There is a delicate balance between the favourable and unfavourable side-effects of screening in general. Overdiagnosis, the detection of breast cancers by screening that would otherwise never have been clinically diagnosed but are now consequently treated, is such an unfavourable side effect. To correctly model the natural history of breast cancer, one has to estimate mean durations of the different pre-clinical phases, transition probabilities to clinical cancer stages, and sensitivity of the applied test based on observed screen and clinical data. The Dutch data clearly show an increase in screen-detected cases in the 50 to 74 year old age group since the introduction of screening, and a decline in incidence around age 80 years. We had estimated that 3% of total incidence would otherwise not have been diagnosed clinically. This magnitude is no reason not to offer screening for women aged 50 to 74 years. The increases in ductal carcinoma in situ (DCIS) are primarily due to mammography screening, but DCIS still remains a relatively small proportion of the total breast cancer problem.     

National comprehensive cancer network recommendations for drugs without US food and drug administration approval in metastatic breast cancer: A cross-sectional study

BackgroundNational Comprehensive Cancer Network (NCCN) guidelines can include recommendations for off-label use of anti-cancer drugs. Here, we evaluate NCCN recommendations not supported by US Food and Drug Administration (FDA) approval and explore associations with such recommendations.MethodsAll NCCN recommendations for MBC and their supporting data were identified. Drug labels were reviewed to determine whether recommendations are FDA approved. Logistic regression was used to compare FDA approved and off-label recommendations for pre-specified categories, including drug type, tumor subtype, level of recommendation and line of therapy.ResultsOf 124 recommendations identified, 68 (55%) were off-label. Chemotherapy and human epidermal growth factor receptor 2 (HER2) targeted drugs were associated with lower odds of FDA approval (OR = 0.28, p = 0.001 and OR = 0.29, 95% p = 0.005, respectively). Recommendations for endocrine therapy (OR = 3.44, p = 0.009) and non-HER2 targeted treatment (OR = 10.0, p < 0.001) were more commonly FDA approved indications. Compared to combination therapies, monotherapies were more likely to be FDA approved (OR = 3.45, p = 0.001) as were category 1 (OR = 7.63, p = 0.001) and preferred NCCN recommendations (OR = 4.07, p < 0.001). Compared to off-label recommendations, NCCN recommendations of approved drugs were based on significantly higher sample size (mean 477 vs. 342 patients, p = 0.02) and were non-significantly associated with availability of randomized data (OR = 2.0, 95% CI 0.89–4.49, p = 0.09).ConclusionMore than half of all NCCN recommendations for MBC are off-label, mostly involving chemotherapy containing regimes for HER2 negative disease and combinations which include HER2-targeted drugs. Improved transparency of NCCN guidelines may result from reporting of the strength of the evidence supporting recommendations for MBC.