免疫治疗研究进展及其在三阴性乳腺癌中的应用CSCD

针对侵袭性强的恶性肿瘤,目前在免疫治疗领域产生了很多潜在的新治疗策略。三阴性乳腺癌研究领域最重要的突破是明确其免疫表型和特征,设计出新的、有针对性的免疫调节靶点来进行治疗。研究最多的是免疫检查点抑制剂的应用,在晚期三阴性乳腺癌解救治疗和早期三阴性乳腺癌新辅助治疗中取得良好疗效。本研究对癌症免疫治疗研究进展及其在三阴性乳腺癌中的应用,尤其是免疫检查点抑制剂与化疗、放疗和靶向治疗联合使用的疗效等进行综述。     

三阴性乳腺癌患者综合治疗的预后分析

目的 探讨三阴性乳腺癌患者综合治疗的预后分析.方法 选择72例三阴性乳腺癌患者(观察组)以及80例非三阴性乳腺癌患者(对照组)作为研究对象,两组患者均经常规的乳腺癌综合治疗,随访5年观察记录两组患者的乳腺癌局部复发、远处转移以及生存情况,进行分析对比.结果 观察组中局部复发40例(55.6％),远处转移30例(41.7％),死亡15例(20.8％);对照组中局部复发18例(22.5％),远处转移8例(10.0％),死亡7例(8.8％);观察组5年局部复发率和远处转移率明显高于对照组,观察组患者5年生存率低于对照组,差异均有统计学意义(P＜0.05).结论 三阴性乳腺癌患者综合治疗后的预后不如非三阴性乳腺癌患者,其具有较高的复发、转移率和死亡风险.     

表柔比星联合紫衫醇治疗三阴性乳腺癌的临床观察

目的 探讨表柔比星联合紫衫醇治疗三阴性乳腺癌的临床效果.方法 85例三阴性乳腺癌患者分为对照组(39例)和观察组(46例),对照组以环磷酰胺联合表阿霉素化疗,观察组患者进行表柔比星联合紫杉醇的新辅助化疗法,治疗结束后对两组有效率、治疗前后肿瘤直径大小、叉头框蛋白A1(FOXAl)和乳腺癌易感基因(BRCAl)蛋白表达水平以及术后不良反应发生情况进行统计.结果 治疗后,对照组和观察组的总有效率分别为64.1%和84.9%,观察组有效率显著高于对照组(P<0.05);在治疗后,两肿瘤直径大小、癌细胞中FOXAl和BRCAI蛋白水平较治疗前均显著下降(P<0.05),且观察组显著低于对照组(P<0.05);观察组和治疗组治疗后不良反应发生率分别为13.0%和17.9%,经比较,无显著性差异(P>0.05).结论 表柔比星联合紫杉醇对三阴性乳腺癌的临床治疗效果显著,且对于肿瘤的缩小,FOXAl、BRCAl水平降低等有显著的效果.     

三阴性乳腺癌的临床病理特征及预后分析

目的探讨三阴性乳腺癌的临床病理特征及生存情况。方法收集2004年1月-2009年12月武汉大学中南医院及湖北省肿瘤医院确诊的乳腺癌患者560例,对比分析三阴性乳腺癌患者情况。结果三阴性乳腺癌多见于绝经前女性,肿瘤直径大,组织学分级高,淋巴结转移率高,5年无瘤生存率及总生存率均低于非三阴性乳腺癌,二者差别有统计学意义。绝经与否、肿瘤直径大小以及淋巴结有无转移与其预后相关。 结论三阴性乳腺癌是一类预后差的乳腺癌亚型。     

Triple Negative Breast Cancer

Triple-negative breast cancers (TNBC), characterized by absence of the estrogen receptor (ER) andprogesterone receptor (PR) and lack of overexpression of human epidermal growth factor receptor 2 (HER2),have a poor prognosis. To overcome therapy limitations of TNBC, various new approaches are needed. Thismini-review focuses on discovery of new targets and drugs which might offer new hope for TNBC patients.     

Nab-Paclitaxel/Bevacizumab/Carboplatin Chemotherapy in First-Line Triple Negative Metastatic Breast Cancer

BackgroundTriple negative metastatic breast cancer can be difficult to treat with primarily cytotoxic options. Nab-paclitaxel has demonstrated improved PFS and tolerability compared with standard cremophor-solubilized paclitaxel; based on this, we examined the efficacy and safety of combining weekly nab-paclitaxel with carboplatin and bevacizumab in TNMBC.Patients and MethodsIn this phase II, multicenter trial, patients with first-line TNMBC received nab-paclitaxel (100 mg/m²) and carboplatin (area under the curve = 2) on days 1, 8, 15, and bevacizumab (10 mg/kg) on days 1 and 15 of a 28-day cycle. The primary end point was safety and tolerability and secondary end points included PFS, ORR, and CBR. PFS was calculated using the Kaplan-Meier method.ResultsBetween July 16, 2007, and October 3, 2011, 34 patients were enrolled at 4 centers. Median age was 50.0 (range, 30-76) years and 77% (n = 26) of patients received previous adjuvant therapy. Median PFS was 9.2 months (95% confidence interval [CI], 7.8-25.1 months). The CBR was 94% (95% CI, 80%-99%), and ORR was 85% (95% CI, 69%-95%) for the combination. The regimen was well tolerated with the most common grade 3/4 adverse events being neutropenia (n = 18; 53%) and thrombocytopenia (n = 6; 18%), with other serous events including 1 grade 3 and 1 grade 4 thrombotic event and 1 febrile neutropenia.ConclusionThe combination of nab-paclitaxel, bevacizumab, and carboplatin as first-line treatment for TNMBC was efficacious and well tolerated. The PFS, CBR, and ORR, and tolerability of the regimen, compares favorably with other standard first-line therapies.     

三阴性乳腺癌的分子分型及应用

三阴性乳腺癌是指雌激素受体、孕激素受体及人表皮生长因子受体均为阴性表达的一类乳腺癌,它是一类具有独特生物学及临床特征的乳腺癌亚型,具有进展快、复发早及预后差的特点。根据三阴性乳腺癌的分子特性,可将其分为六种基因表达亚型。研究表明三阴性乳腺癌基因表达亚型和特定的基因突变亚型之间存在重要关联,这一发现可能为不同亚型的三阴性乳腺癌的个体化治疗提供重要的治疗靶点。本文将概括目前对于三阴性乳腺癌亚型分类的认识,以及这种分类在将来临床实践中的应用。     

178例三阴性乳腺癌的临床病理特征及生存分析

 目的
探讨三阴性乳腺癌(TNBC)患者的临床病理特点、生存情况和预后影响因素。方法收集雌激素受体(ER)、孕激素受体
(PR)和人表皮生长因子受体2(HER2)均阴性的178例乳腺癌患者的临床病理资料,观察其长期生存状况。分析其临床
特点及影响预后的因素。结果有乳腺癌家族史的患者4例。主要病理类型为浸润性导管癌(155/178,87.1%）。组织
学分级多为Ⅲ级(53.1%）。中位肿瘤最大径2.8 cm(0.2～12 cm）,T1、T2期患者160例占89.9%。108例(61.7%）
患者无淋巴结转移。分期为Ⅰ、Ⅱ、Ⅲ期的患者分别有60例(33.7％)、81例(45.5％)、31例(17.4％)。58例(48.3
％)患者p53阳性。中位随访时间74月(10～156月）,5年
无病生存(DFS)和总生存(OS)率分别是76.9%和86.1%。单因素分析显示T分期、临床分期及淋巴结转移对DFS和OS
均有显著影响。多因素分析显示,淋巴结转移是DFS及OS的独立影响因素。而术后分期是OS的影响因素。共有41例
患者出现复发转移及第二原发肿瘤,常见转移部位依次为骨转移、局部复发或同侧锁骨上淋巴结转移、肺或胸膜转
移、肝转移及脑转移。结论 本组TNBC肿瘤直径较小,组织学分级低分化比例较高(53.1%）。复发转移以骨转移、
局部复发及肺转移为主。淋巴结转移及术后分期是总生存的独立危险因素。     

三阴性乳腺癌临床病理特点及与EGFR表达关系的探讨*

目的:研究三阴性乳腺癌的临床病理特点、预后及与EGFR 表达的关系。方法:回顾性分析天津医科大学总医院1997年1 月至2004年1 月200 例乳腺癌患者的临床资料,总结其病理特征及随访结果,并将200 例病例对应的石蜡标本制作成组织芯片,用免疫组织化学法检测乳腺癌组织中ER、PR、HER-2 的表达,进行乳腺癌分子分型。检测EGFR 蛋白的表达,分析其与乳腺癌病理特征及预后的关系。结果:200 例乳腺癌患者中三阴性乳腺癌42例（21.00%）,在患者年龄、肿瘤大小、临床分期、淋巴结状态等病理参数的分析中,三阴性乳腺癌与非三阴性乳腺癌的分布无明显差异,而在绝经状态及肿瘤组织学分级的分析中,三阴性乳腺癌与非三阴性乳腺癌差异有统计学意义（P<0.05）。 三阴性乳腺癌患者中17例死亡（生存率59.52%）,非三阴性患者26例死亡（生存率83.54%）,二者有显著性差异（P<0.05）。 EGFR 在三阴性乳腺癌中表达率较高（69.05%）,与肿瘤组织学分级及淋巴结转移密切相关,且表达EGFR 的三阴性乳腺癌患者生存时间较短。结论:三阴性乳腺癌发病率虽然不高,但其与常规的乳腺癌预后相关因素缺乏特定联系,患者预后差。EGFR 在三阴性乳腺癌中高表达,可作为三阴性乳腺癌的一个重要的预后指标,并为临床提供了治疗的靶点。      

Impact of Triple Negative Phenotype on Prognosis and Early Onset of Breast Cancer in Iranian Females

Background: Breast cancer in Iranian women occurs about a decade earlier than in Western countries. Thisstudy sought to evaluate the impact of triple negative phenotype on early onset of ductal cell breast cancer and itsprognosis in Iranian females. Methods: Estrogen and progesterone receptors, Her-2 overexpression and nuclearaccumulation of P53 were assessed in sixty surgically resected formalin-fixed paraffin embedded breast invasiveductal carcinomas. They were divided into triple negative and non triple negative phenotypes and impact of thephenotypes were evaluated on prognostic factors of all patients and based on menopausal status. Results: Theresult showed that the mean age of patients with triple negative breast tumors, especially in postmenopausalgroup, was significantly lower than with non triple negative phenotypes. Although the latter was significantlyassociated with higher histological grade, it also showed a significant correlation with smaller size of tumor anda lower rate of axillary lymph node metastasis in young patients. Conclusion: The higher rate of breast cancerwith triple negative phenotype in Iranian females is a feasible reason for the reported lower mean age of breastcancers. In premenopausal patients, triple negative phenotype reveals a positive impact on prognostic factors,but it is associated with a poorer prognosis in postmenopausal patients. Hence, a distinct ethnic profile of triplenegative phenotype in Iranian females is suggested.     

三阴性乳腺癌与非三阴性乳腺癌临床病理特征比较及预后因素分析

目的探讨三阴性乳腺癌与非三阴性乳腺癌相关的临床病理特征和预后影响因素。方法收集184例乳腺癌患者的临床资料和病理资料。将患者随机分为2组,A组(三阴性乳腺癌)60例与B组(非三阴性乳腺癌)124例。对2组患者地体质特征和肿瘤特征进行比较,并对184例患者的预后结果进行分析。结果 A组和B组患者在发病年龄,乳腺癌家族史,肿瘤大小,肿瘤组织学分级,淋巴结阳性和转移状态方面存在显著差异。同时,2组在5年,7年和9年无病生存率及7年,9年总生存率方面,差异有统计学意义。结论三阴乳腺癌与发病年龄、家族遗传史、肿瘤大小、腋窝淋巴结阳性率、肿瘤组织学分级有关,癌症转移风险高,预后差。     

Differential Association of the Lifestyle-Related Risk Factors Smoking and Obesity with Triple Negative Breast Cancer in a Brazilian Population

Background: A longer lifespan and changing lifestyle-related and reproductive risk factors have led to an increased incidence of breast cancer in Brazil. There have been few studies about associations of specific risk factors with molecular subtypes of the disease. The aim of the present study was to identify factors that modulate the risk of triple negative breast cancer. Materials and Methods: A case-case analysis was performed. Data for 236 breast cancer patients from two reference centres in North-eastern Brazil were applied to assess the association of risk factors with triple negative breast cancer relative to the luminal A subtype. Molecular subtypes were defined by expression status of hormone receptors and amplification of HER2. Nominal logistic regression was used to estimate odds ratios and to generate a model of independent variables. Results: Smoking and body mass index were differentially associated with likelihood of triple negative breast cancer compared to the Luminal A subtype (p= 0.013; p= 0.004): Women who ever smoked some time in their lives were 4.016 (OR= 0.249; CI 95%: 0.09- 0.71) times less likely to have triple negative breast cancer. Obese and overweight patients, respectively, were 4.489 (CI 95%: 1.32- 15.28) and 1.340 (CI 95%: 0.38- 4.69) times more likely to have triple negative breast cancer. Conclusions: Case-case analysis with the Luminal A subtype as the reference group indicated that smoking and body mass index are differentially associated with risk of triple negative breast cancer.     

Eight Year Survival Analysis of Patients with Triple Negative Breast Cancer in India

Background: Triple-negative breast cancer (TNBC) often presents as an interval cancer with short survival upon metastasis and thus represents an important clinical challenge. The present study investigated the clinicopathologic characteristics and long term survival outcome of early and locally advanced TNBC. Materials and Methods: Medical records were reviewed retrospectively for 148 consecutive confirmed cases of TNBC treated in a single unit at our centre. Demographic profile, tumor type, histopathology details, treatment and follow-up information was recorded and immunohistochemistry was performed. Results: Age group >50 years was associated with tumors of clinical stage 3 (53.8%), pathological stage 3 (46.2%), pathological grade 3 (45.7%), presence of extracapsular extension (ECE, 48.5%) and lymphovascular invasion (LVI, 64.9%). Locally advanced breast cancers (LABCs) were characterized by pathological stage 3 (96.2%), presence of ECE (100%) and absence of LVI (46.7%) as compared to early breast cancers (EBCs) which had higher incidence of lower stage tumors (100%), absence of ECE (82%) and presence of LVI (91.9%; p-value Conclusions: TNBCs are aggressive tumors which show poor long term survival. Patients with TNBC benefit from chemotherapy, thus better and less toxic treatment options are needed. Identification of newer targets and development of targeted therapies are the need of the hour.     

Neoadjuvant Chemotherapy in Triple Negative Breast Cancer: Correlation between Androgen Receptor Expression and Pathological Response

Background: There is growing evidence that the response to chemotherapy may be affected by Androgen Receptor (AR) expression suggesting that triple-negative breast cancers (TNBC) AR+ and quadruple negative breast cancer (QNBC) subtypes may have different diseases behavior. Methodology: We retrospectively estimated the predictive value of the AR expression in stage II and stage III TNBC patients treated with neoadjuvant chemotherapy (NAC) and correlated with the rate of pathological response (pCR). Results: Of 89 TNBC patients, 29 patients (32.6%) were TNBC AR+ and 60 patients (67.4) were QNBC. Most of the patients were less than 60 years old. Of note, approximately 62% in the QNBC group were less than 40 years old compared with 39 % in the TNBC AR+ group. The Ki-67 expression was higher in the QNBC in comparison with TNBC AR+ being 86.7% and 65.5%, respectively. QNBC subgroup showed higher rates of pCR compared with TNBC; 60% and 24%, respectively. Higher Ki-67 expression, higher grade, and lymph node involvement were statistically significantly correlated with the rate of pCR in the QNBC group (p=0.02, p=0.04, and p=0.03, respectively). In contrast, no significant association was observed between pCR and clinical-pathological features in the TNBC AR+ group. Conclusion: Our results suggested that the AR expression in TNBC may be applied as a predictive marker for NAC. TNBC AR+ had a lower rate of pCR compared with QNBC, suggesting that this subtype may have a partial chemoresistance.     

EGFR、Ki67在三阴性与非三阴性乳腺癌中的表达及其与TNBC病理特征的相关性

目的 探讨EGFR、Ki67在三阴性与非三阴性乳腺癌中的表达差异及两者的表达与TNBC临床病理特征的关系.方法 分析non-TNBC与TNBC患者的临床病理资料,采用非生物素二步法检测76例乳腺癌标本里EGFR、Ki67的表达,对比两者在non-TNBC与TNBC中的区别.检测EGFR与Ki67在TNBC中的阳性表达率,研究其与病理参数的相关性.结果 和non-TNBC相比,TNBC多见于绝经前妇女,组织学分级较差,较易发生淋巴结转移、复发转移、远处转移,且出现较早.EGFR与Ki67在TNBC组织中的阳性表达率均高于在non-TNBC组织中的阳性表达率.EGFR、Ki67的表达与TNBC肿块直径、淋巴结转移情况、TNM分期、组织学分级之间均具有相关性.结论 EGFR与Ki67在TNBC中表达均升高.两者的表达与肿块直径、淋巴结转移情况、TNM分期、组织学分级之间均具有相关性.     

Triple Negative Apocrine Carcinomas as a Distinct Subtype of Triple Negative Breast Cancer: A Case-control Study

Background

Invasive triple negative apocrine carcinoma (TNAC) of the breast is a rare type of triple negative breast cancer. Several studies reported significantly distinct prognosis for TNAC when compared with most of the non-apocrine triple negative (NATN) tumors. This is a case-control study reporting onoutcomes from our long-term single-center experience.

沉默LncRNA WT1-AS对三阴性乳腺癌细胞MDA-MB-231侵袭和迁移的影响

目的 探讨LncRNA WT1-AS对三阴性乳腺癌细胞MDA-MB-231侵袭和迁移的影响.方法 qRT-PCR检测WT1-AS在三阴性乳腺癌细胞中的表达及基因沉默的效率;Transwell实验检测WT1-AS对MDA-MB-231细胞侵袭能力的影响;划痕实验检测WT1-AS对MDA-MB-231细胞迁移能力的影响;W...     

Triple Negative Breast Cancer in People of North East India: Critical Insights Gained at a Regional Cancer Centre

Background: Breast cancer is a heterogeneous disease comprising of distinct biological subtypes with manytargeted prognostic biomarkers having therapeutic implications. However, no specific targeted therapy fortriple negative breast cancer has been discovered to date and hence further research is needed. Aim: The aimand objectives of the present study were to examine the prevalence of triple negative breast cancer (TNBC)in North-East India and to compare the clinicopathological parameters in two study groups defined byimmunohistochemistry (IHC) –“TNBC” and “Others”. Materials and Methods: We carried out a retrospectivestudy in a cohort of 972 patients diagnosed with invasive breast carcinoma in the Department of Pathology, Dr.B. Borooah Cancer Institute, a Regional Cancer Centre for treatment and research, Guwahati, for a period of 3years and 10 months from January 2010 to October 2013. Based on IHC findings, patients were divided into twogroups - “TNBC” and “Others”. All relevant clinicopathological parameters were compared in both. TNBC weredefined as those that were estrogen receptor (ER), progesterone receptor (PR), and HER2/neu negative whilethose positive for any of these markers were defined as “Others”. Results: In this study, out of total 972 cases31.9% (310 cases) were defined as TNBC and 662 cases (68.1%) as “Others” based on IHC markers. Comparedto the “Others” category, TNBC presented at an early age (mean 40 years), were associated with high gradelarge tumours and high rate of node positivity, IDC NOS being the most common histological subtype in TNBC.Conclusions: TNBC accounts for a significant portion of breast cancers in this part of India and commonlypresent at younger age and tend to be large high grade tumours.