基于靶标指导乳腺癌精准治疗标志物临床应用专家共识（2022版）

 乳腺癌是一种分子水平异质性很高的恶性肿瘤,病理分型结合分子标志物成为常规诊断方式。分子分型可助力乳腺癌的分类分层精准治疗,但在临床实践中乳腺癌标志物的检测方法、评价体系与临床解读等尚存在一定局限性。为了进一步促进基于靶标指导的乳腺癌精准治疗,中国抗癌协会肿瘤标志专业委员会乳腺癌标志物协作组组织临床、病理、分子检测等领域专家,综合国内外乳腺癌临床应用共识和指南、重要文献及临床实践编写本共识,对基于靶标指导乳腺癌精准治疗给出专家组意见,以期提高临床上以标志物为靶标的乳腺癌精准诊断和治疗水平,为乳腺癌患者的系统治疗提供新视野。      

乳腺癌的分子分型与肿瘤治疗的相关性

乳腺癌是女性最常见的肿瘤之一,因其肿瘤组织具有高度异质性、多种组织亚型,因而产生不同临床表现、不同治疗反应以及不同预后.传统评价乳腺癌预后的因素包括:发病年龄、肿瘤大小、临床分期、淋巴结转移等.近年来,基于基因表达谱不同提出的乳腺癌分子分型研究不断深入,为乳腺癌的个体化治疗提供了一个有力的依据.本文从乳腺癌的固有分子分型入手,描述不同分子分型的特点及其临床结局的差异,着重阐述不同分子分型与乳腺痛局部复发的关系,同时对其他分子分型进行简要分析,以期对乳腺癌分子分型有一个全面的了解并为临床治疗方案的制定提供依据.     

乳腺癌基因表达谱研究进展

乳腺癌是分子表达差异显著的一组疾病,乳腺癌临床异质性源自分子异质性.根据基因表达谱研究开发的分子标签,如70-基因标签、21-基因标签、乳腺癌分子分型标签等,在预测乳腺癌患者预后、指导临床治疗决策方面,表现出良好的应用价值和前景.     

激素受体阳性乳腺癌治疗进展

化疗和内分泌治疗是雌激素受体和（或）孕激素受体阳性乳腺癌治疗的主要手段。肿瘤负荷因素、多基因标记物检测、肿瘤分子分型可用于指导乳腺癌患者是否需要化疗。不同内分泌治疗策略各有自身价值,不能相互取代。临床实践中应对Luminal A型和Luminal B型两种不同类型乳腺癌提供个体化治疗。     

分子分型在乳腺癌放疗中的价值及应用

摘 要：乳腺癌作为高度分子异质性疾病,根据雌、孕激素受体及Her-2的表达可分为4型。研究显示不同的分型具有明显不同的临床特征,根据分子分型指导患者接受化疗、内分泌治疗或靶向治疗。随着对其研究的深入,越来越多的报道显示分子分型可以指导乳腺癌的放疗。     

乳腺癌的分子分型

乳腺癌是多基因参与、多步骤发生的恶性肿瘤,基因表达谱的不同使得乳腺癌具有不同的生物学特征,而乳腺癌的异质性导致了病理分期相同的患者对临床治疗的反应及预后会有很大差别.确定一种能够准确反映乳腺癌治疗疗效及预后的分型,对于进行个体化治疗和改善乳腺癌患者的预后具有重要意义.基因芯片技术的开发利用,以及2004年完整人类基因图的公布[1],推动了乳腺癌分子分型的研究.下面就目前已发现的基于基因表达的乳腺癌分子分型加以评述.     

新疆乳腺癌分子分型的临床病理学意义

目的:回顾性分析新疆维吾尔自治区人民医院病理科确诊的乳腺癌病理资料,探讨新疆地区不同分子分型乳腺癌的临床病理意义.方法:收集2011 年 1 月至2014 年 12 月就诊于新疆维吾尔自治区人民医院并行改良根治手术的 406 例乳腺癌患者的临床病理资料,根据雌激素受体ER、孕激素受体PR、人表皮生长因子受体-2 (HER-2)和 Ki-67 增殖指数进行分子分型,比较不同分子亚型乳腺癌患者的临床病理特征.结果:luminal A型中组织学分级I级最常见,luminal B型发病年龄较luminal A型年轻、但组织学分级更高,淋巴结转移更常见,HER-2过表达型淋巴结转移率最高,三阴性型组织学分级III级比例最高.不同分子分型乳腺癌在肿块大小、组织学分级方面的差异均显示统计学意义(P<0.05).结论:新疆地区luminal B 型乳腺癌更常见,HER-2 过表达型比例最低.联合组织学分类和分子分型,更有助于指导乳腺癌的诊断和治疗.     

乳腺癌分子标志及分子分型研究进展

乳腺癌是常见恶性肿瘤.随着分子生物学的快速发展与生物检测技术的不断涌现,乳腺癌分子标志及分子分型愈来愈受到人们的广泛重视,临床上结合乳腺癌的分子分型对乳腺癌进行个体化治疗已成为可能.本文就雌激素受体（ER）、黄体酮受体（PR）、人表皮生长因子受体2（HER-2）、及Ki-67等乳腺癌分子标志的临床应用现状及乳腺癌分子分型的临床研究进展进行综述.     

基因分型对乳腺癌诊治和预后判断的指导作用

乳腺癌是女性的常见恶性肿瘤之一,其临床治疗主要是以经典的TNM和临床分期为指导。近年来兴起的对乳腺癌相关的分子遗传学研究取得了令人瞩目的进展,提出了乳腺癌基因分型这一新概念。基因诊断对乳腺癌的辅助化疗以及预后的判断相对传统的病理分型有更高的专一性,为乳腺癌的治疗起到了更好的指导作用,本文主要对基因分型进行介绍并总结了几种与乳腺癌预后相关的基因标志,探讨其在临床治疗中的实际应用。     

分子分型指导下的乳腺癌个体化放疗

分子分型概念作为乳腺癌个体化综合治疗发展史上的一个里程碑,量化地定义了乳腺癌不再是单一疾病,而是在发病风险、自然病程、治疗反应等方面迥异的一组异质性疾病。分子分型对全身治疗的疗效预测及对全身转移和死亡风险的预后价值均已得到广泛的研究验证,但它与LRR风险的相关性,以及对放疗策略的指导作用也尚需要更多关注。本综述将就分子分型与LRR风险的相关性,以及分子分型对放疗策略的指导价值展开讨论。     

乳腺癌血清肿瘤标志物和循环肿瘤细胞检测的研究进展

 随着分子生物学的发展,乳腺癌的治疗正逐步进入分子分型治疗的时代,为了给患者提供更加有效的个体化治疗,研究者们不断努力寻找乳腺癌新的治疗靶点、疾病监控指标以及疗效预测和预后评估的指标,日益深入的研究显示血清肿瘤标志物和循环肿瘤细胞的检测在乳腺癌治疗中有重要价值。现就近年乳腺癌血清肿瘤标志物和循环肿瘤细胞检测的相关临床研究作一综述。     

Exploring molecular pathways of triple-negative breast cancer

Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype with a high rate of proliferation and metastasis, as well as poor prognosis for advanced-stage disease. Although TNBC was previously classified together with basal-like and BRCA1/2-related breast cancers, genomic profiling now shows that there is incomplete overlap, with important distinctions associated with each subtype. The biology of TNBC is still poorly understood; therefore, to define the relative contributions of major cellular pathways in TNBC, we have studied its molecular signature based on analysis of gene expression. Comparisons were then made with normal breast tissue. Our results suggest the existence of molecular networks in TNBC, characterized by explicit alterations in the cell cycle, DNA repair, nucleotide synthesis, metabolic pathways, NF-κB signaling, inflammatory response, and angiogenesis. Moreover, we also characterized TNBC as a cancer of mixed phenotypes, suggesting that TNBC extends beyond the basal-like molecular signature and may constitute an independent subtype of breast cancer. The data provide a new insight into the biology of TNBC.     

A new look at molecular biology of breast cancer

In the past 25 years, incidence rates of breast cancer have risen about 30% in westernized countries. Mutations in BRCA1 and BRCA2 are the most prominent cause of breast cancer. However, these cancer susceptibility genes (BRCAs) only account for a few percent of women suffering breast tumor. With our understanding that BRCAs are Fanconi Anemia (FA) genes, investigations into the FA signaling network should provide a previously unrecognized key to unlock in-depth insights into both etiology and treatment of breast cancer. Here, we discuss utilization of the FA signaling as a unique genetic model system to expand our knowledge about the molecular biology of breast cancer and potential applications of the gained knowledge to enable preventive and therapeutic approaches for breast cancer patient care.     

乳腺癌耐药机制研究进展和应对策略

乳腺癌是女性最常见的恶性肿瘤之一,其分型的多样性与临床治疗密切相关。近年来随着分子生物学的快速发展,乳腺癌的治疗进展迅速,效果显著,但治疗方案产生的耐药仍是临床一线治疗最常遇到的问题。本文就不同类型的乳腺癌及其临床特征进行了分类分析,针对不同分型的治疗方案和耐药机制进行了总结和探讨,旨在通过研究治疗的分子机制和可能存在的耐药机制,对临床治疗起到引导作用。     

三阴乳腺癌治疗研究进展

Triple-negative breast cancers (TNBCs) neither express estrogen receptor and progesterone receptor nor overexpress human epidermal growth factor receptor-2. Because of the special molecular features, triple-negative breast cancer is not either sensitive to endocrine therapy or targeted therapy of trastuzumab. There has not been standard treatment regimen for triple-negative breast cancer yet and chemotherapy has still been the chief therapy currently. However, with the great progress of oncology and molecular biology, the understanding of the natural history, pathophysiology and molecular features of this disease has been greatly improved, and a growing number of novel and effective therapies and discoveries of new biological targets for this phenotype of breast cancers have been reported, which provide new insights into therapeutic strategies for the women suffering from it.     

Advances in molecular imaging for breast cancer detection and characterization

Advances in our ability to assay molecular processes, including gene expression, protein expression, and molecular and cellular biochemistry, have fueled advances in our understanding of breast cancer biology and have led to the identification of new treatments for patients with breast cancer. The ability to measure biologic processes without perturbing them in vivo allows the opportunity to better characterize tumor biology and to assess how biologic and cytotoxic therapies alter critical pathways of tumor response and resistance. By accurately characterizing tumor properties and biologic processes, molecular imaging plays an increasing role in breast cancer science, clinical care in diagnosis and staging, assessment of therapeutic targets, and evaluation of responses to therapies. This review describes the current role and potential of molecular imaging modalities for detection and characterization of breast cancer and focuses primarily on radionuclide-based methods.     

乳腺癌分子生物学特性检测的临床意义

目的探讨乳腺癌细胞增殖活性、bcl2和突变型p53蛋白表达水平的临床意义。方法应用流式细胞术检测121例乳腺癌的DNA倍体、S期细胞百分比(SPF)及bcl2和突变型p53表达阳性率,结合雌激素受体测定和66例乳腺浸润性导管癌的组织学分级进行统计学分析。结果66例乳腺浸润性导管癌组织Ⅰ、Ⅱ、Ⅲ级间异倍体阳性率、DNA指数(DI)差异均有统计学意义(P均<0.01)。乳腺癌组织Ⅰ、Ⅱ、Ⅲ级的SPF分别为(1.84±1.02)%、(2.44±1.07)%和(2.71±1.16)%,差异有统计学意义(P<0.05);突变型p53表达阳性率分别为(1.03±1.11)%、(2.91±1.61)%和(3.37±2.13)%,差异有统计学意义(P<0.05);bcl2阳性表达率差异无统计学意义(P>0.05),但癌组织与正常组织间差异有统计学意义。雌激素受体阳性与阴性两组间,SPF分别为(2.17±1.04)%和(4.56±1.77)%,突变型p53蛋白表达阳性率分别为(2.93±1.63)%和(4.39±2.73)%,差异均有统计学意义(P<0.05),而bcl2表达阳性率差异无统计学意义(P>0.05)。DI、SPF和p53表达阳性率两两相关,DI与SPF、DI与p53表达阳性率、SPF与p53表达阳性率的相关系数分别为0.73,0.40和0.42(P均<0.01);bcl2表达阳性率与各指标之间无相关关系。结论突变型p53和bcl2与乳腺癌的发生有一定关系;异倍体率、DI与突变型p53表达阳性率可以提示肿瘤预后;流式细胞术检测可以作为病理诊断的补充;乳腺癌患者可术前通过流式细胞术检测提示预后,确立治疗模式。     

Novel therapeutic approaches to the treatment of metastatic breast cancer

Metastatic breast cancer is ultimately an incurable disease, although recent data have shown that its incidence is decreasing and that patients with metastatic breast cancer live longer. This improvement in survival seems to be linked with the introduction of new therapeutic agents, novel combinations of existing therapies and targeted therapies. Our increasing understanding of the molecular biology of metastatic disease has allowed the development of therapies aimed at specific molecular targets. Some of these have already been approved for the treatment of metastatic breast cancer in combination with cytotoxics, and others have shown promising results regarding disease-free survival, overall response rates and time to disease progression. Given the enormous amount of information about drug discovery in cancer, it is important to be familiar with the present state of the treatment of metastatic breast cancer. The purpose of this review is to provide an update on the development of some of the most promising novel agents and treatment strategies in metastatic breast cancer.     

Cytogenetic and molecular biologic alterations in human breast cancer: A review

Summary Chromosomal and molecular biologic studies of human breast cancer are beginning to provide insight into the basic biology of this important disease. The current state of knowledge of both cytogenetic evaluation and assessment of expression and amplification of cellular oncogenes in breast cancer will be outlined in this brief review.J.M.T. is supported in part by PHS grants CA-29476 and CA-17094 awarded by the National Cancer Institute, Bethesda, Maryland.     

双侧原发性乳腺癌的分子生物学特征

目的:探讨双侧原发性乳腺癌(bilateral primary breast cancer,BPBC)的分子生物学特征。方法:回顾性分析325例BPBC与650例单侧乳腺癌(unilateral breast cancer,UBC)患者的临床病理资料,应用单因素分析和Logistic回归多因素分析,寻找BPBC发生的相关分子生物学依据。结果:与UBC患者比较,BPBC患者第一癌发病年龄早、有乳腺癌家族史、肿瘤直径>5cm及临床Ⅲ期患者较多(P均<0.05)。在分子生物学特征方面,BPBC第一癌患者雌激素受体(estrogen receptor,ER)和孕激素受体(progesterone receptor,PR)阴性比率、p53阳性率和细胞增殖核抗原Ki67高表达者均高于UBC患者(P<0.05);人表皮生长因子受体2(human epidermal growth factor receptor2,Her-2)表达在二者间的差异无统计学意义(P>0.05)。其中乳腺癌家族史、肿瘤直径>5cm、p53阳性为BPBC发生的独立危险因素,ER(+)或PR(+)者发生BPBC的风险下降。结论:BPBC与UBC在生物学行为上存在一定的差异,对于年轻、有乳腺癌家族史、激素受体阴性,p53阳性及Ki67高表达的乳腺癌患者要注意检查对侧乳腺癌的发生。