乳腺癌的分子分型

乳腺癌是1种严重威胁女性健康的常见恶性肿瘤,近年来罹患此病的患者逐年增多。临床上发现组织学类型和病理分期相同的患者,在临床表现、治疗反应性和预后等方面有相当大的差异,其原因在于乳腺癌存在不同的分子分型。目前分子生物学技术的发展日益迅猛,同时随着人类完整基因图谱的公布,乳腺癌分子分型的研究被越来越多的肿瘤学者关注。     

乳腺癌分子分型在新辅助化疗疗效及预后预测中的作用

目的:探讨乳腺癌分子分型在新辅助化疗疗效及预后预测中的作用.方法:收集漯河市中心医院收治的236例接受新辅助化疗患者的临床病理资料,分为Luminal A、Luminal B、Her-2阳性和三阴乳腺癌4种分子分型,分析分子分型与临床病理因素、新辅助化疗疗效及 5 年生存率的相关性.结果:236例患者中,107例(45.3%)为Luminal A亚型,47例(19.9%)为Luminal B亚型,27例(11.4%)为Her-2阳性亚型,55例(23.3%)为三阴乳腺癌亚型.Her-2阳性(25.9%)及三阴乳腺癌亚型(30.9%)的病理完全缓解(pCR)率明显高于Luminal亚型(Luminal A亚型 4.7%及Luminal B亚型 8.5%),差异有统计学意义(P<0.05).与Luminal亚型相比,Her-2阳性及三阴乳腺癌亚型具有更差的5年无病生存和总生存(P<0.01);获得pCR的乳腺癌患者的5年无病生存和总生存明显高于化疗后仍有癌残留的患者(P<0.05).结论:相对于Luminal亚型,Her-2 阳性和三阴乳腺癌亚型对新辅助化疗更为敏感,更易达到pCR;但是Her-2阳性和三阴乳腺癌亚型预后反而更差.     

基于乳腺癌分子分型的个体化治疗进展

乳腺癌治疗的成熟模式一直是多学科的综合治疗,即手术、化疗、放疗、内分泌治疗及分子靶向治疗。然而乳腺癌患者之间存在明显的异质性,即使是组织学类型、分期都相同的乳腺癌,使用同一标准化治疗方案,疗效及预后仍存在很大差异,因此对乳腺癌患者进行个体化治疗显得尤为重要。     

原发性乳腺癌分子分型与新辅助化疗疗效及预后的相关性

目的 探讨原发性乳腺癌分子分型与新辅助化疗疗效及预后之间的相关性。方法 回顾性分析河南省肿瘤医院收治的204例接受新辅助化疗患者的临床病理资料,分为Luminal A、LuminalB、HER2阳性和三阴乳腺癌4种亚型,分析乳腺癌分子分型对新辅助化疗疗效及预后的预测作用。结果 204例患者中,40例（19.6％）为Luminal A亚型,46例（22.5％）为Luminal B亚型,36例（17.6％）为HER2阳性亚型,82例（40.2％）为三阴乳腺癌亚型。HER2阳性（22.2%）及三阴乳腺癌亚型（22.4%）的病理完全缓解（pCR）率明显高于Luminal A亚型（2.5％）及Luminal B亚型（6.5％）,差异有统计学意义（P=0.03）。与Luminal亚型相比,HER2阳性及三阴乳腺癌亚型具有更差的无病生存期（DFS）（P=0.001）和OS（P=0.002）;剔除获得pCR的患者,单独评价存在肿瘤残留的患者,我们发现HER2阳性及三阴乳腺癌亚型比Luminal亚型具有更差的DFS（P<0.001）和OS（P<0.001）。获得pCR的乳腺癌患者的5年DFS和总生存期（OS）均明显高于化疗后仍有癌残留的患者（P=0.002, P=0.012）。结论 相对于Luminal亚型,HER2 阳性和三阴乳腺癌亚型对新辅助化疗更为敏感,更易达到pCR;但是HER2阳性和三阴乳腺癌亚型预后反而更差。     

腋窝淋巴结阴性浸润性乳腺癌分子分型的表达及预后分析

  目的   探讨腋窝淋巴结阴性浸润性乳腺癌不同分子分型的分布,临床病理特征以及和预后的关系。   方法   回顾性分析183例该类乳腺癌患者的临床病理资料,对管腔上皮（Luminal）型、基底样（Basal-1ike）型和HER-2过表达（over-expression）型乳腺癌患者在年龄、肿瘤大小、临床分期和无瘤生存率（disease-free survival,DFS）、总生存率（overall survival,OS）方面进行统计分析。   结果   不同分子亚型乳腺癌在年龄、肿瘤大小、临床分期方面无显著性差异。Luminal、Basal-like、HER-2过表达型的复发率分别为3.9%（4/102）、20.4%（10/49）、6.3%（2/32）（P=0.002）;死亡率分别为2.0%（2/102）、6.1%（3/49）、3.1%（1/32）（P>0.05）。Ka-plan-Meier分析显示Basal-like型的DFS最低（P=0.002）,Basal-like型的OS较低（P=0.39）。Cox多因素比例风险模型分析显示分子亚型对DFS存在显著影响（P=0.001）。   结论   在腋窝淋巴结阴性浸润性乳腺癌患者中,不同分子亚型在年龄、肿瘤大小及临床分期方面无显著性差异,Basal-like型预后最差,分子分型是其独立预后指标。       

不同分子分型乳腺癌的临床病理特征及预后的关系

目的 探讨乳腺癌分子分型与临床病理特征及预后的关系.方法 选择126例乳腺癌患者,按孕激素受体(PR)、雌激素受体(ER)和人类表皮生长因子受体-2(HER-2)的状态分为Luminal A型、Luminal B型、HER-2过度表达型和Basal-like型,比较不同分子分型乳腺癌患者的临床病理特征、复发转移及预后情况.结果 156例乳腺癌患者中,Luminal A型68例(54.0%)、Luminal B型22例(17.5%)、HER-2过度表达型9例(7.1%)、Basal-like型27例(21.4%).乳腺癌不同分子分型间绝经状态、肿瘤直径、淋巴结转移数目、临床分期及组织学分级的差异均有统计学意义(P<0.05).HER-2过度表达型与Basal-like型的局部复发率分别为33.3%和14.8%,远处转移率分别为55.6%和40.7%,均高于其他2种亚型,差异均有统计学意义(P<0.05).4组中位无瘤生存时间的差异有统计学意义(χ2=8.002,P<0.05),HER-2过度表达型与Basal-like型的MPFS较短.结论 HER-2过表达型和Basal-like型乳腺癌的病理学特征较差,且预后不良;而Luminal A型预后较好.     

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.     

分子分型与乳腺癌新辅助化疗疗效的相关性

目的:探讨乳腺癌分子分型与新辅助化疗疗效的相关性.方法:回顾性分析81例原发乳腺癌患者,分子分型分为HER-2阳性型和三阴型、Luminal A型、Luminal B1型、 Luminal B2型,并评估其与乳腺癌新辅助化疗疗效的关系.结果:新辅助化疗疗效与各分子分型之间的相关性无统计学意义,但新辅助化疗有效率达到pCR+tpCR(%)以三阴型最高(25%),其次是HER-2阳性型(23.1%),而达到CR+PR(%)为HER-2阳性型最高(84.6%).结论:乳腺癌新辅助化疗可有效控制肿瘤,分子分型能作为乳腺癌新辅助化疗疗效的缓解独立预测因子.     

不同分子分型乳腺癌患者预后与淋巴结转移率的相关性分析

[摘要] 目的: 探讨不同分子分型乳腺癌患者预后与Ⅱ、Ⅲ期乳腺癌淋巴结转移率的相关性。方法: 回顾性分析2011 年1 月至2016 年1 月在南京医科大学附属常州第二人民医院311 例确诊为Ⅱ、Ⅲ期乳腺癌并首选手术治疗的乳腺癌患者的临床资料,依据雌激素受体（ER）、孕激素受体（PR）、人类表皮生长因子受体-2（HER2）和Ki-67 增殖指数分为Luminal A型、Luminal B 型、HER2 过表达型和三阴型（TNBC）4 型。通过卡方检验分析不同分组间患者的临床特征;通过Kaplan-Meier 生存曲线评估腋淋巴结转移率（LNR）对各型乳腺癌患者预后的影响,以及相同LNR的不同分子分型的乳腺癌预后的差异,通过Spearman 相关分析LNR与Ki-67 增殖指数的相关性。结果: 不同分子分型在患者年龄、绝经情况、肿瘤大小、淋巴结状态及转移部位等临床特征差异无统计学意义（均P>0.05）。LNR为0 或>0.65 的4 组分子分型的无病生存时间（DFS）差异无统计学意义（χ2=3.581、2.808,均P>0.05）,LNR介于0.01~0.65 的4 组分子分型的DFS差异有统计学意义（χ2=24.366、8.169,均P<0.05）。LNR与Ki-67 增殖指数呈正相关（r=0.125,P<0.05）。多因素Cox 回归分析显示,乳腺癌患者预后与分子分型（RR=1.179,95%CI=1.023~1.358;χ2=5.165,P<0.05）、LNR（RR=1.137,95%CI=0.985~0.999;χ2=5.589,P<0.05）及Ki-67 增殖指数（RR=0.992,95%CI=1.022~1.264;χ2=5.623,P<0.05）有关。结论: LNR是Ⅱ、Ⅲ期乳腺癌预后的重要影响因素,相同LNR的不同分子分型预后差异显著,LNR与Ki-67 增殖指数呈正相关。     

腋窝淋巴结阴性浸润性乳腺癌的分子分型及预后观察

目的探讨腋窝淋巴结阴性浸润性乳腺癌患者的分子分型及其预后情况。方法回顾性分析2006年12月至2009年6月间180例腋窝淋巴结阴性浸润性乳腺癌的临床病理资料,并按照雌激素受体(ER)、孕激素受体(PR)及人类表皮生长因子受体-2(HER-2)的检测结果将其分为管腔上皮(Luminal)型、基底样(Basal-like)型及HER-2过表达(over-expression)型,观察不同分型乳腺癌在不同年龄、肿瘤大小及分期中的表达及预后情况。结果 180例腋窝淋巴结阴性浸润性乳腺癌患者中,Luminal型、Basal-like型、HER-2过表达型分别占54.4%(98/180)、27.8%(50/180)和17.8%(32/180)。Luminal型、Basal-like型、HER-2过表达型在不同年龄、肿瘤大小及临床分期中的表达差异无统计学意义(P>0.05)。Basal-like型患者术后36和60个月的转移率分别为14.0%和36.0%,高于Luminal型的3.1%、20.4%及HER-2过表达型的6.3%、21.9%,差异有统计学意义(P<0.05)。Basal-like型患者术后60个月的死亡率为24.0%,高于Luminal型(10.2%)及HER-2过表达型(15.6%),HER-2过表达型患者术后60个月的死亡率高于Luminal型,差异有统计学意义(P<0.05)。结论腋窝淋巴结阴性浸润性乳腺癌的分子分型以Lumina1型最为常见,Basal-like型与HER-2过表达型构成比较低,其中Basal-like型患者预后较差,其次为HER-2过表达型患者。     

Prognostic effect analysis of molecular subtype on young breast cancer patients

Objective

To make a prognostic effect analysis of molecular subtype on young breast cancer patients.

Methods

Totally 187 cases of young breast cancer patients less than 40 years old treated in Obstetrics and Gynecology Hospital of Fudan University between June 2005 and June 2011 were included in our study. We described their clinical-pathological characteristics, disease-free survival (DFS) rate, and overall survival (OS) rate after a median follow-up period of 61 months. The factors associated with prognosis were also evaluated by univariate and multivariate analyses.

Results

All patients were premenopausal, with an average age of 35.36±3.88 years old. The mean tumor size was 2.43±1.53 cm. Eighty-one cases had lymph node metastasis (43.3%), 126 cases had lymphovascular invasion (67.4%), and 125 cases had histological grade III (66.8%) disease. Twenty-seven cases (14.4%) were Luminal A subtype, 99 cases (52.9%) were Luminal B subtype, 29 cases (15.5%) were human epidermal growth factor receptor 2 (HER-2) overexpression subtype, while 32 cases (17.1%) were triple negative breast cancer (TNBC) subtype according to 2013 St Gallen expert consensus. One hundred and thirty-five cases underwent mastectomy whereas 52 cases had breast-conserving surgery. One hundred and seventy-eight cases underwent adjuvant or neoadjuvant chemotherapy. Recurrence or metastasis occurred in 29 cases, 13 of which died. The 5-year DFS and OS rates were 84% and 92%. Multivariate analysis showed that nodal status (P=0.041) and molecular subtype (P=0.037) were both independent prognostic factors of DFS, while nodal status (P=0.037) and TNBC subtype (P=0.048) were both independent prognostic factors of OS.

Conclusions

Molecular subtype is an independent prognostic factor of young breast cancer patients. TNBC has a high risk of relapse and death.     

云南省乳腺癌分子分型与临床病理特点分析

目的：了解云南省乳腺癌患者的分子分型与临床病理特点.方法：收集2012年1月-2012年12月云南省肿瘤医院乳腺病科所收治的经根治性手术后病理确诊为原发性乳腺癌的初诊患者587例,统计分析分子分型与患者年龄、民族、病理类型、病灶大小、淋巴结分期、病理分期、p53等的相关性.结果：不同民族、病灶大小、淋巴结分期、p53表达与分子分型之间差异无统计学意义.不同年龄段与分子分型之间差异有统计学意义,P=0.033.不同病理类型与分子分型之间差异有统计学意义,P=0.022.不同病理分期与分子分型之间差异有统计学意义,P=0.004.结论：云南省乳腺癌不同年龄段、不同病理分期的分子分型存在差异.     

Immunological subtypes in breast cancer are prognostic for invasive ductal but not for invasive lobular breast carcinoma

Background:

Classical patient and tumour characteristics are the benchmark of personalised breast cancer (BC) management. Recent evidence has demonstrated that immune and molecular profiling of BC may also play an important role. Despite evidence of differences between invasive ductal (IDC) and lobular (ILC) BC, they are infrequently accounted for when making treatment decisions for individual patients. The purpose of this study was to investigate the relevance of the tumour immune response in the major histological subtypes of BC. We also assessed the relationship between immune responses and molecular subtypes and their prognostic potential.

Methods:

Immunostains were done for HLA-I, HLA-E, HLA-G, Tregs, NK cells and CTLs for the composition of the immune profiles and Ki67, EGFR, CK5/6, ER, PR and HER2 for molecular profiles in 714 breast cancer patients who underwent primary surgery.

Results:

No significant association was found between IDC (90.6%) and ILC (9.4%) and tumour immune subtypes (P=0.4) and molecular subtypes (P=0.4). However, for the relapse-free period (RFP) tumour immune subtyping was prognostic (P=0.002) in IDC, but not ILC. Contrary to ILC, IDC patients frequently expressed higher cleaved caspase-3 and Ki67, which was prognostic. Intermediate immune-susceptible IDC expressing high cleaved caspase-3 or Ki67 showed worse RFP than those with low expression (caspase-3: P=0.004; Ki67: P=0.002); this was not seen for ILC or in high or low immune-susceptible tumour types for either IDC or ILC.

Conclusions:

Tumour immune characteristics and host immune responses are prognostic in IDC, but not ILC. In addition, tumour immune profiles are only prognostic in Luminal A tumours.     

Predictive role of molecular subtypes in response to neoadjuvant chemotherapy in breast cancer patients in Northeast China

Introduction: Breast cancer is increasingly regarded as a heterogeneous disease which can be classified into distinct molecular subtypes with prognostic significance. Materials and methods: ER, PR, HER2 and ki-67 were used to divided 102 breast cancers treated with neoadjuvant chemotherapy ( NCT ) into 4 subtypes: luminal A (ER+,PR+,HER2-, and ki-67 ≤14%), luminal B (ER+, PR+,HER2- and ki-67>14% ; ER+ and/or PR+, HER2+), HER2-overexpression (ER-, PR- and HER2+) and triple-negative (ER-, PR-,and HER2-). Results: Among 102 patients, a pCR was seen in 16 (15.7%) patients. The pathologic complete remission (pC) rates according to different subtypes are as follows: luminal A, 0 of 20 (0.0%), luminal B, 2 of 23 (8.7%), HER2-overexpressio,n 4 of 18 (22.2%), and triple-negative, 10 of 41 (24.4%) (p=0.041). In triple-negative subtype patients, the rates of pCR differed significantly among the 3 chemotherapy regimens with 5.6% (1/18) for CEF (cyclophosphamide, epirubicin and flurouracil), 20.0% (1/5) for TE (docetaxel and epirubicin) and 44.4% (8/18) for TCb (docetaxel and carboplatin) (p=0.024). In locally advanced breast cancer patients, the rates of pCR seem to differ among the 3 chemotherapy regimens with 6.7% (2/30) for CEF, 0.0% (0/8) for TE and 23.1% (6/26) for TCb, but this did not attain statistical significance (p>0.05). Conclusions: Molecular subtypes are good predictors for response to NCT in breast cancer patients in Northeast China. Compared with luminal A tumors, HER2-overexpression and triple-negative subtypes are more sensitive to NCT. For triple-negative breast cancer, we concluded that the TCb combination is a promising NCT regimen. Our results also indicated that the TCb combination is promising for the treatment of locally advanced breast cancer.     

Anthropometric factors and risk of molecular breast cancer subtypes among postmenopausal Norwegian women

Adult height and body weight are positively associated with breast cancer risk after menopause, but few studies have investigated these factors according to molecular breast cancer subtype. A total of 18,562 postmenopausal Norwegian women who were born between 1886 and 1928 were followed up for breast cancer incidence from the time (between 1963 and 1975) height and weight were measured until 2008. Immunohistochemical and in situ hybridization techniques were used to subtype 734 incident breast cancer cases into Luminal A, Luminal B [human epidermal growth factor receptor 2 (HER2?)], Luminal B (HER2+), HER2 subtype, basal‐like phenotype (BP) and five‐negative phenotype (5NP). We used Cox regression analysis to assess adult height and body mass index (BMI) in relation to risk of these subtypes. We found a positive association of height with risk of Luminal A breast cancer (p_trend, 0.004), but there was no clear association of height with any other subtype. BMI was positively associated with risk of all luminal breast cancer subtypes, including Luminal A (p_trend, 0.002), Luminal B (HER2?) (p_trend, 0.02), Luminal B (HER2+) (p_trend, 0.06), and also for the HER2 subtype (p_trend, 0.04), but BMI was not associated with risk of the BP or 5NP subtypes. Nonetheless, statistical tests for heterogeneity did not provide evidence that associations of height and BMI differed across breast cancer subtypes. This study of breast cancer risk among postmenopausal women suggests that height is positively associated with risk of Luminal A breast cancer. BMI is positively associated with risk of all luminal subtypes and for the HER2 subtype.     

218例不同分子亚型浸润性乳腺癌患者的临床特征

目的：探讨浸润性乳腺癌分子亚型在中国人群中的分布,以用于判断临床预后和指导治疗。方法：回顾分析218例浸润性乳腺癌患者,根据雌激素受体（ER）、孕激素受体（PR）、人类表皮生长因子受体2（HER2）的水平划分为4个分子亚型。对比分析4型患者的分布比例、发病年龄、病理组织学分类、肿瘤最大径以及淋巴结转移等相关因素。结果：在4型中,luminal A型例数最多,共131例（60.1%）;basal-like型共有63例（28.9%）;luminal B型和HER2过表达型所占比例较少,均为12例（5.5%）。发病年龄以40岁～59岁年龄段发生乳腺癌例数最多,达到77.06%。HER2过表达型在50岁～59岁年龄段发病例数显著增高,与其余3组相比有显著性差异（P〈0.05）。病理分类显示,浸润性导管癌最多,各型之间无显著性差异（P〉0.05）;从淋巴结阳性病例中,HER2过表达型和luminal B型多枚淋巴结转移比例更高（P〈0.05）。肿瘤最大径分析显示,HER2过表达型和basal-like型病例肿瘤最大径2cm～5cm的比例较高,而luminal A型和luminal B型的肿瘤最大径多小于2cm（P〈0.05）。结论：在4型中,luminal A型所占比例最高;HER2过表达型在50岁～59岁年龄段发病较多见;浸润性导管癌是最常见的病理组织类型;HER2过表达型和luminal B型多枚淋巴结转移情况更多发生;HER2过表达型和basal-like型肿瘤较luminal A型更大。     

肿瘤浸润淋巴细胞对不同分子亚型乳腺癌预后效应的研究进展

肿瘤浸润淋巴细胞（tumor infiltrating lymphocytes,TILs）是肿瘤微环境的重要组分，对结肠癌、肺癌等多种肿瘤预后有明确的指示效应。在乳腺癌中，相关研究的结论并不一致。考虑到乳腺癌是一组由多种不同分子亚型组成的异质性疾病，TILs对不同分子亚型乳腺癌的预后指示作用也不同。本综述阐述常用TILs指标对不同分子亚型乳腺癌预后指示效应的相关研究进展。