三阴性乳腺癌5年随访

Objective: The aim of the study was to investigate the long-term therapeutic effects of triple negative breast cancers (TNBCs) and find a standardized treatment. Methods: The clinical data and survival status of 69 patients with TNBC were collected, who were treated from 2003 to 2007 at Chongqing Cancer Institute, China. Results: Median observation for 61 months showed the local recurrence rate was 13.0% (9/69), the overall survival (OS) rate was 76.8% (53/69) and the disease free survival (DFS) rate was 59...     

Triple negative breast cancer - prognostic factors and survival

Background

Triple negative breast cancer (TNBC) is defined by a lack of expression of both estrogen (ER) and progesteron (PgR) receptors as well as human epidermal growth factor receptor 2 (HER2). Our retrospective analysis addressed prognostic factors for short- and long-term outcomes of patients (pts) with TNBC pts treated in routine clinical practice.

Patient and methods.

Our retrospective study included 269 TNBC treated at Institute of Oncology Ljubljana between March 2000 and December 2006. The collected data included patients’, tumours’ and treatments’ characteristics. The survival analyses were performed using the Kaplan-Meier method. The Cox proportional hazard model was used in the multivariate analysis.

Results

The median age of our patients was 55.3 yrs (23–88.5) and the median follow-up was 5.9 yrs (0.3–9.6). Six (2%) pts experienced local only, 79 (92%) pts distal recurrence and 66 (24%) died. The predominant localisation of the first relapse was in visceral organs (70.4%). The 5-year disease-free survival (DFS) for the entire group was 68.2% and the 5-year overall survival (OS) was 74.5%. We found a pattern of high recurrence rate in the first 3 years following the diagnosis and a clear decline in recurrence rate over the next 3 years. In the univariate analysis age, nodal status, size and lymphovascular invasion (LVI) were found to have a significant impact on DFS as well as on OS. In the multivariate analysis only age (HR=1.79; 95%CI=1.14–2.82; p=0.012) and nodal status (HR=2.71; 95%CI=1.64–4.46; p<0.001) retained their independent prognostic value for DFS and for OS only the nodal status (HR=2.96; 95%CI=1.51–5.82; p=0.002).

Conclusions

In our series of TNBC pts nodal status and age (older than 65 yrs) were found to be independent prognostic factors for DFS, whereas for OS only the nodal status. We found a pattern of a high recurrence rate in the first 3 years following the diagnosis and a decline in the recurrence rate over the next 3 yrs with higher rate of distal versus local recurrence and a predominant localization of distal metastases in visceral organs.     

E-钙黏附蛋白表达与乳腺癌及三阴性乳腺癌预后的相关性研究

目的探讨E-钙黏附蛋白表达对判断乳腺癌及三阴性乳腺癌预后的意义。方法用随机数字法调取本院2003～2005年浸润性乳腺癌（浸润性小叶癌除外）280例,用免疫组化法检测E．钙黏附蛋白表达情况。Log Rank法对比生存曲线,分析E-钙黏附蛋白表达与乳腺癌及三阴性乳腺癌预后的相关性。结果在280例乳腺癌患者中,E-钙黏附蛋白表达阴性患者较E-钙黏附蛋白表达阳性患者预后差（生存率对比Log Rank=19．99,P=0．00;无瘤生存率对比Log Rank=21．42,P=0．00）。在32例三阴性乳腺癌患者中,E-钙黏附蛋白表达阴性患者较E．钙黏附蛋白表达阳性患者预后差（生存率对比Log Rank=4．67,P=0．03;无瘤生存率对比：Log Rank=6．54,P=0．01）。结论E-钙黏附蛋白是乳腺癌及三阴性乳腺癌的预后因子,有助于进一步划分三阴性乳腺癌的亚型。     

三阴性乳腺癌与表观遗传学研究现状

目的：探讨表观遗传修饰在三阴性乳腺癌（triplenegativebreastcancer,TNBC）检测、诊断和靶向治疗中的机制及作用。方法：应用PubMed、CNKI全文数据库及Google学术搜索等检索系统,以“乳腺癌或三阴性乳腺癌和表观遗传学或DNA甲基化”等为关键词,检索2003—01—2013-12的相关文献,共检索到英文文献1055爷,中文文献35条。纳入标准：1）TNBC癌诊断与治疗;2）表观遗传学修饰机制;3）表观遗传学对TNBC癌的意义。根据纳入标准,符合分析的文献47篇。结果：DNA甲基化、组蛋白修饰及miRNA调控在TNBC的发生、发展中扮演重要角色,通过表观遗传修饰与TNBC相关基础研究的总结,以及在已有的实验研究或临床研究的基础上进行理论推测,对TNBC的临床诊断、预后和治疗具有借鉴意义。结论：通过研究表观遗传学修饰改变在TNBC发生、发展中的作用,可为将来TNBC患者的临床治疗提供新思路。     

Safe selection criteria for breast conservation without radical excision in primary operable invasive breast cancer

In a previous series from this unit of 263 women with primary operable breast cancer treated by macroscopic lumpectomy and breast irradiation, local recurrence was high. An audit at a median follow up of 36 months showed 56 (21%) ipsilateral breast recurrences. Eighteen of these recurrences were aggressive and uncontrolled. Multivariate analysis shows patient age, lymphovascular invasion, tumour size and nodal status to be predictive of local recurrence (Locker AP, et al., Br J Surgery 1989, 76, 890–894). New selection criteria for breast conservation were defined based on these data and also on securing an adequate clear margin of excision. In a subsequent prospective series of 275 women fulfilling these criteria, 6 women (2.2%) developed ipsilateral breast recurrence at the same median follow up of 36 months. In none was this uncontrolled and aggressive. Breast conservation, without radical excision, is safe as long as the selection criteria described are followed.     

小剂量口服沙利度胺对三阴性乳腺癌患者凝血系统功能的影响

目的:观察三阴性乳腺癌患者服用小剂量沙利度胺前后凝血指标变化,以探讨小剂量沙利度胺是否能增加栓塞事件风险。方法:选取2008年至 2012年于中国医科大学附属盛京医院住院的三阴性乳腺癌患者292例,将患者按治疗过程中是否进行化疗分为化疗组（145例）与非化疗组（147例）,均给予沙利度胺100mg每日一次口服。服药前和连续服用沙利度胺3个月、6个月后抽取患者外周静脉血,用4色荧光流式细胞仪检测血小板活化程度,自动分析凝血仪检测患者部分凝血活酶时间（APTT）、凝血酶原时间（PT）、纤维蛋白原（FIB）、D-二聚体（DD）。比较患者血小板活化程度、内外源性凝血途径功能变化。结果:收治的292例患者,去除退组的55例,服用沙利度胺前后APTT、PT值、血小板活化程度均无显著变化。化疗组服沙利度胺前FIB为（3.4±0.92）g/L,DD值为（242.7±249.7）μg/L;服沙利度胺6个月后FIB为（3.9±2.4）g/L（t=-2.48,P=0.021）,DD值为（354.2±236.1）μg/L(t=-2.1,P=0.047)。FIB、DD值较前升高,有显著意义。非化疗组FIB值较前升高,但无显著意义(t=-1.83,P=0.078),服药前DD值为（225.6±156.8）μg/L,之后为（267.3±206.7）μg/L,升高有显著意义(t=-2.69,P=0.012)。结论:小剂量口服沙利度胺不能影响三阴性乳腺癌患者血小板活化,亦不能影响内外源凝血因子,但有可能增加深静脉血栓发生几率。     

三阴性乳腺癌中MMP-9的表达及意义

目的:探讨三阴性乳腺癌(TNBC)中基质金属蛋白酶-9(MMP-9)的表达及意义.方法:收集2012年1月至2013年12月乳腺浸润性导管癌共158例,应用免疫组织化学及荧光原位杂交技术将乳腺癌分为65例TNBC、93例非TNBC.免疫组织化学检测MMP-9的表达情况,明确MMP-9在二组间表达的区别.分析MMP-9在TNBC中与临床病理特征关系,并随访65例TNBC患者3年复发或转移率,探讨MMP-9表达与3年复发转移率间的关系.结果:TNBC中MMP-9表达明显高于非TNBC(P<0.05);TNBC中MMP-9表达与年龄和肿瘤大小无关(P>0.05),与TNM分期、组织学分级、淋巴结状态及脉管浸润有关,差异具有统计学意义(P<0.05);MMP-9阳性的TNBC患者3年复发转移率高达76.09%,明显高于MMP-9阴性组47.37%,差异具有统计学意义(P<0.05).结论:TNBC中MMP-9表达明显高于非TNBC,MMP-9与TNBC浸润转移有关,对预测3年复发转移有明显意义.     

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.     

Triple negative breast cancer: looking for the missing link between biology and treatments

The so called “Triple Negative Breast Cancer” (TNBC) represents approximately 15-20% of breast cancers. This acronym simply means that the tumour does not express oestrogen receptor (ER) and progesterone receptor (PR) and does not exhibit amplification of the human epidermal growth factor receptor 2 (HER2) gene. Despite this unambiguous definition, TNBCs are an heterogeneous group of tumours with just one common clinical feature: a distinctly aggressive nature with higher rates of relapse and shorter overall survival in the metastatic setting compared with other subtypes of breast cancer. Because of the absence of well-defined molecular targets, cytotoxic chemotherapy is currently the only treatment option for TNBC.In the last decades, the use of more aggressive chemotherapy has produced a clear improvement of the prognosis in women with TNBC, but this approach results in an unacceptable deterioration in the quality of life, also if some support therapies try to relieve patients from distress. In addition, there is the general belief that it is impossible to further improve the prognosis of TNBC patients with chemotherapy alone. In view of that, there is a feverish search for new “clever drugs” able both to rescue chemo-resistant, and to reduce the burden of chemotherapy in chemo-responsive TNBC patients.A major obstacle to identifying actionable targets in TNBC is the vast disease heterogeneity both inter-tumour and intra-tumour and years of study have failed to demonstrate a single unifying alteration that is targetable in TNBC. TNBC is considered the subtype that best benefits from the neoadjuvant model, since the strong correlation between pathological Complete Response and long-term Disease-Free-Survival in these patients.In this review, we discuss the recent discoveries that have furthered our understanding of TNBC, with a focus on the subtyping of TNBC. We also explore the implications of these discoveries for future treatments and highlight the need for a completely different type of clinical trials.     

Triple negative breast carcinoma EGFR amplification is not associated with EGFR,Kras or ALK mutations

Background:

The amplification of epidermal growth factor receptor (EGFR) in triple negative breast carcinomas (TNBC) suggests its potential therapeutic application, as for HER-2, using standardised methods of measurement. In this regard, we aimed to compare several methods for evaluating EGFR amplification along with potential mutations for suitability in clinical practice.

Methods:

Tissue sections of 138 TNBCs were used (1) to compare EGFR amplification and expression by silver in situ hybridisation (SISH) to qPCR and immunohistochemistry (IHC) and (2) to search for EGFR mutations, along with Kras, PI3K, Braf and HER-2 mutations and echinoderm microtubule associated protein like 4-anaplastic lymphoma kinase (EML4-ALK) translocation.

Results:

(1) Amplification of EGFR was observed in well-characterised TNBCs (up to 92%); (2) qPCR correlated with SISH with 94% specificity and 75.6% sensitivity; (3) IHC correlated with SISH with 97% sensitivity and 78% specificity; (4) no EGFR, Kras mutations or EML4-ALK translocations were found, but PI3K and Braf mutations were observed in 26% of cases; and (5) small, acentric circular extrachromosomal DNA similar to ‘double minutes'' in glioblastomas was observed in 18% of SISH sections.

Conclusions:

SISH and IHC are methods that are suitable in clinical practice to screen for EGFR amplification and overexpression, which are frequently observed in TNBC. Patients with TNBC are potential candidates for EGFR-targeted therapy combined with PI3K and Braf inhibitors.     

It is possible to omit postoperative irradiation in a highly selected group of elderly breast cancer patients

The purpose of this study was the evaluation of the necessity of routinely applied postoperative radiotherapy in a highly selected patient-group after breast conserving surgery. Between 1983 and May 1994, 356 women over 60 years of age with Stage I or II breast cancer were treated by quadrantectomy and axillary dissection followed by either adjuvant irradiation or no radiotherapy. We have analysed our data retrospectively to investigate whether irradiation has any benefit in elderly patients with respect to locoregional recurrence rates. After a median follow-up of 60 months the multivariate model revealed lymph node status (p=0.002) as highly significant with regard to local recurrence free survival. We were not able to identify a positive effect of adjuvant irradiation in patients with negative lymph nodes and positive receptor status: both patient groups with or without irradiation had similar locoregional recurrence rates of 3%. In a subgroup of patients who were lymph node negative, receptor positive, and received adjuvant tamoxifen therapy, the local recurrence rates were as low as 2% in both groups. Concerning these results it may be possible to avoid the morbidity and potential psychological side effects of radiotherapy in breast cancer patients over 60 years of age treated by breast conserving surgery (T1, N0, positive hormone receptor, adjuvant tamoxifen) without increasing risk of locoregional recurrence. These data have to be confirmed in a prospectively randomized fashion.     

三阴性乳腺癌及其研究进展

三阴性（雌激素、孕激素受体与HER-2均为阴性）乳腺癌是具有特殊生物学行为及临床病理特征的一个乳腺癌亚型,与基底样乳腺癌和BRCA1相关性乳腺癌有一定相关性。此类型乳腺癌对放化疗尚比较敏感,但常规标准治疗疗效欠佳,预后较其他类型乳腺癌差。目前针对其BRCA1、EGFR等基因及其功能异常而开展的相应研究正在进行。     

复发转移性三阴性乳腺癌临床特征及总生存分析

目的：分析复发转移性三阴性乳腺癌患者的治疗方式及总生存情况。方法回顾性分析复发转移后来我院治疗,并随访至病亡的78例三阴性乳腺癌患者临床资料,根据其临床特征、复发情况及治疗方式评价其总生存情况。结果78例患者总生存时间（OS）为6～236个月,中位OS为32.1个月。1年生存率92.3%,5年生存率28.2%,10年生存率6.4%。71例（91.0%）三阴性乳腺癌患者行根治术或改良根治手术,其无病生存时间（DFS）为1～184个月,中位DFS为15.0个月,7例（9.0%）患者为初治Ⅳ期。Ⅰ期三阴性乳腺癌患者OS为19.7～236个月,中位OS为90.0个月。复发转移后OS为3.0～93.3个月,中位OS为14.4个月。13例（16.7%）患者局部复发或单纯部位转移的患者行局部手术治疗联合全身治疗者中位OS为26.5月,65例（83.3%）仅行全身治疗者中位OS为12.2个月（P=0.034）。一线化疗方案含紫杉类药物的患者中位OS为14.6个月,未予紫杉类药物的患者中位OS为11.0个月（P=0.048）。结论复发转移性三阴性乳腺癌整体预后较差,生存期短,但异质性较高,且早期三阴性乳腺癌患者具有明显的生存优势。值得一提的是本文只针对已经有生存节点的患者进行分析,这组患者乳腺癌的恶性程度相对较高。也间接提示三阴性乳腺癌的治疗也不能一概而论。对这些早期复发的患者,目前的辅助治疗可能是不足够的。     

Subtyping of triple‐negative breast cancer: Implications for therapy

Triple‐negative breast cancer (TNBC) is a heterogeneous disease; gene expression analyses recently identified 6 distinct TNBC subtypes, each of which displays a unique biology. Exploring novel approaches for the treatment of these subtypes is critical, especially because the median survival for women with metastatic TNBC is less than 12 months, and virtually all women with metastatic TNBC ultimately will die of their disease despite systemic therapy. To date, not a single targeted therapy has been approved for the treatment of TNBC, and cytotoxic chemotherapy remains the standard treatment. In this review, the authors discuss recent developments in subtyping TNBC and the current and upcoming therapeutic strategies being explored in an attempt to target TNBC. Cancer 2015;121:8–16 . © 2014 American Cancer Society.     

The 10-Year Local Recurrence and Partial Breast Radiotherapy for Early Breast Cancer Treated by Conservative Surgery

C onservative surgery for early breast cancer was proposed by Keynes in 1924 and has been one of the main therapeutic mea- sures. It has been confirmed by abundant literature that the efficacy of conservative surgery plus whole breast radiotherapy is the …     

铂类药物用于三阴性乳腺癌的新辅助化疗

三阴性乳腺癌(triple-negative breast cancer,TNBC)作为乳腺癌的一个亚型,其复发率较高而总生存率低。尽管其对于包含蒽环类和紫衫类药物为基础的新辅助化疗方案反应显著,但预后较差。目前尚未发现专门的分子及化疗药物作用靶点。铂类并非是治疗三阴性乳腺癌的常规用药,本文对铂药物用于三阴性乳腺癌新辅助化疗的现状进行综述。