IHC和FISH联合检测278例浸润性乳腺癌中HER-2状态的研究

目的：同时应用免疫组织化学（IHC）和荧光原位杂交（FISH）技术,检测278例浸润性乳腺癌组织中的人类表皮生长因子受体2（Human Epidermal Growth Factor Receptor2,HER-2）,以探讨两种方法检测HER-2状态的符合率。方法：用IHC和FISH法分别检测278例浸润性乳腺癌组织中HER-2蛋白的表达和HER-2基因状态,以比较两种方法的阳性率和准确率。结果：IHC和FISH检测HER-2的总符合率为83.9%,Kappa系数为0.650（P〈0.001）。130例IHC标记HER-2结果显示为＋＋的病例中,44例（33.8%）Fish为阳性,54例结果1HC为阳性或＋的病例中的5例（9.3%）,经FISH检测证实HER-2基因有扩增。而94例IHC结果显示为＋＋＋的病例中,有3例（20.2%）FISH结果为阴性。在130例IHC显示＋＋的病例中,3例FISH结果为模棱两可。结论：IHC和FISH检测HER-2的符合率为83.9%,对IHC标记HER-2结果为＋＋的病例,用FISH检测大多能得到满意结果。对极少数HER-2基因扩增为临界状态的乳腺癌病例需结合其他检查结果综合考虑。     

Histopathologic characteristics predicting HER-2/neu amplification in breast cancer

The HER-2/neu gene is a proto-oncogene that is amplified in 10-30% of breast cancers. New drugs for targeted therapy, such as Herceptin, are effective for patients with HER-2/neu-positive tumors, making it necessary to have a noncostly and accurate method to assess HER-2/neu status. We studied the correlation of findings made by fluorescent in situ hybridization (FISH) and immunohistochemistry (IHC) staining and the possibility of combining IHC and other clinicopathologic characteristics of breast tumors to predict FISH-determined HER-2/neu status. The clinicopathologic characteristics analyzed were the size of the tumor, p53, lymph-vascular invasion, estrogen/progesterone receptors (ER/PR), tumor grade, axillary lymph node status, and patient age. A total of 199 cases of invasive breast cancer studied at the UCLA Pathology Laboratory during 2003 were included in this study. Tumors with IHC 0, 1+, 2+, and 3+ scores were found to be FISH positive in 3.5%, 6.4%, 25.7%, and 81.5% of the respective groups. Our study showed a strong association between the FISH-negative and IHC scored 0 and 1+ tumors, suggesting that the FISH test may not be necessary in these cases (p<0.0001). Although the concordance between IHC 3+ and FISH positive is high, 18% of the patients with overexpression of HER-2/neu fail to show gene amplification by FISH. HER-2/neu positivity was found to be proportionally associated with increasing grade in infiltrating ductal carcinoma (p<0.0001). p53-positive tumors are more likely to be HER-2/neu amplified (p=0.0003). Tumors that are negative for ER/PR are also associated with HER-2/neu positivity by FISH (31.15%, p=0.0016). FISH-determined HER-2/neu status is not associated with histologic type, tumor size, nodal status, lymph-vascular invasion, or patient age.     

Impact of 2013 ASCO/CAP guidelines on HER2 determination of invasive breast cancer: A single institution experience using frontline dual-color FISH

PurposeThe new ASCO/CAP guidelines published in 2013 (AC2013) significantly modified the scoring criteria for HER2-FISH, introducing the most controversial change to the HER2-equivocal category. We retrospectively evaluated the impact of AC2013 in a cohort of consecutive invasive breast cancers (IBCs) analyzed with frontline dual-color FISH.Methods2788 consecutive IBCs were reclassified based on the AC2013 guidelines. Clinico-pathological features of equivocal IBCs were compared with HER2-negative and HER2-positive IBCs. FISH HER2-equivocal cases underwent reflex tests: HER2-IHC, RARA-FISH, and SMS-FISH. Overall and disease-free survivals were evaluated in AC2007 HER2-positive patients treated with trastuzumab and in patients that became eligible for target-therapy according to AC2013.ResultsTwo-hundred HER2-negative cases (7.2%) were classified differently, following AC2013: 0.3% (8/2788) became HER2-positive and 6.9% (192/2788) HER2-equivocal. AC2013, compared with AC2007, significantly increased initial HER2-equivocal cases (6.9%vs1.6%, p < 0.001). AC2013 equivocal-IBCs affected older patients and showed pathological features between HER2-negative and HER2-positive IBCs. After reflex tests, 102 of the 190 equivocal cases (53.7%) were reclassified as HER2-positive, 51 (26.8%) as negative and 37 (19.5%) as equivocal. IHC tested negative in 44.7% of cases, whereas SMS-FISH showed the highest percentage of positive results (45.8%). Clinical outcomes showed no statistically significant differences.ConclusionOverall, 80.5% of FISH-equivocal cases were solved with at least one reflex test and 3.6% of patients became AC2013 HER2-positive, therefore eligible for target-therapy, but showed clinical outcomes similar to HER2-positive patients treated with trastuzumab.Our data belittle the clinical impact of AC2013 HER2-equivocal reclassification; further prospective randomized clinical studies are necessary to support these findings.     

乳腺癌中HER-2基因的扩增及意义

目的 研究乳腺浸润性导管癌HER-2基因的扩增情况及其与乳腺癌临床病理因素的关系。方法 采用荧光原位杂交法（FISH）检测254例乳腺浸润性导管癌组织中HER-2基因的扩增情况,分析其与乳腺癌的肿瘤大小、组织学分级、腋淋巴结转移情况、病理分期、雌、孕激素受体表达以及该基因蛋白表达等的关系。结果 FISH检测到254例乳腺癌中有175例发生HER-2基因高扩增,该基因高扩增与乳腺癌的肿瘤大小、组织学分级、病理分期、腋淋巴结转移数、雌孕激素受体表达、HER-2蛋白表达均有关（P均＜0.05）,与患者的年龄无关 (P＞0.05)。结论 乳腺癌中HER-2基因的高扩增导致其蛋白过度表达,HER-2基因高扩增与乳腺癌的生长、恶性程度有关,是判断乳腺癌生物学行为的重要指标。联合检测HER-2基因扩增情况及其他指标有助于指导临床判断乳腺癌预后并制定治疗方案。     

三阴性乳腺癌与HER-2过表达乳腺癌患者的临床病理特征及预后比较

目的 探讨三阴性乳腺癌与HER-2过表达乳腺癌患者的l临床病理特征及预后.方法 回顾1997年1月至2007年1月行手术治疗的725例原发性乳腺癌的临床资料,根据免疫组化染色结果确定三阴性和HER-2过表达乳腺癌表型,并对2组的临床病理学资料进行比较和生存分析.结果 三阴性和HER-2过表达乳腺癌分别占12.29%及24.96%;三阴性乳腺癌有恶性肿瘤家族史者占18.4%,明显高于HER-2过表达组的5.5%(P=0.001);组织学分级3级者占54.0%,也高于HER-2过表达组42.0%(P=0.01);三阴性乳腺癌(74.7%)较HER-2过表达乳腺癌(64.6%)更易发生淋巴结转移(P=0.045);在2年内复发、转移及脑转移(分别为25.3%及8.0%)明显高于HER-2过表达乳腺癌(分别为8.8%和2.2%)(P<0.05),其5年无病生存率(55.6%)明显低于HER-2过表达乳腺癌(69.8%)(P=0.041).2组在年龄、月经状态、肿瘤大小、病理分期、手术方式、病理类型、辅助放化疗、肝肺骨转移比例和总生存率之间差异均无统计学意义(P>0.05).结论 与HER-2过表达乳腺癌相比,三阴性乳腺癌更多有恶性肿瘤家族史,肿瘤恶性度更高,更易发生淋巴结和脑转移,无病生存期更短,预后差.     

紫杉醇类辅助化疗对HER-2阳性乳腺癌患者生存率影响的研究

目的探讨含紫杉醇类辅助化疗方案对HER-2(表皮生长因子受体2)阳性乳腺癌患者生存率的影响。方法选取2001年5月至2004年10月我院乳腺肿瘤中心HER-2阳性的早期乳腺患者191名,随访至疾病进展,分析她们的临床特征(年龄,手术方式)和病理学特征(激素受体状态,HER-2状态),化疗方案与生存率的关系。结果平均随访29.8个月,总复发转移率12.57%(24/191),平均疾病进展时间27.17个月。其中用只含蒽环类辅助化疗者无病存活率80/96=83.33%,含紫杉醇类辅助化疗者无病存活率97.10%(67/69)(字2=35.67,P<0.001)。其中ER、PR均阴性者99人,用只含蒽环类化疗复发转移24.07%(13/54),含紫杉醇类化疗复发转移2.86%(1/35)(字2=101.10,P<0.0001)。结论含紫杉醇类药物进行术后辅助化疗能增加HER-2阳性乳腺癌患者无病生存获益,尤其是对ER、PR均阴性且HER-2阳性者。     

FISH与IHC检测414例乳腺癌Her-2基因表达状态的比较

目的比较荧光原位杂交(FISH)和免疫组织化学(IHC)检测乳腺癌Her-2基因扩增情况的一致性与相关性。方法分别采用FISH和IHC检测414例乳腺癌组织Her-2基因扩增的情况,对两种方法检测结果进行统计学比较分析。结果两种方法检测结果有统计学差异(P=0.000),与FISH的一致性在IHC检测c-erbB-2(+++)和(-～+)组较好Kappa值=0.643,两者一致率为83.2%,而在c-erbB-2(++)组一致性较差。结论 IHC可以作为初步筛查乳腺癌Her-2基因状态的首选方法。在c-erbB-2(+++)和(+～-)中常可以用IHC代替FISH检测HER-2基因扩增状况,而对于c-erbB-2(++)则应常规进行FISH检测。     

Distribution of hsp-27 and HER-2/neu in in situ and invasive ductal breast carcinomas

Background: The overexpression of heat shock protein 27 (hsp-27) in early-stage breast cancer is associated with histopathologic features of poor prognosis and clinically with an increased probability of disease recurrence. Hsp-27 is overexpressed in 25% of invasive ductal carcinomas (IDC); however, its distribution in ductal carcinoma in situ (DCIS) and DCIS associated with IDC has not been investigated. We postulated that hsp-27 might be detected and variably expressed in DCIS and, like HER-2/neu oncoprotein expression, might be a tumor-specific marker worthy of future clinical investigation. Methods: To test these hypotheses, the distribution of hsp-27 in noncomedo and comedo DCIS, and DCIS associated with IDC, was evaluated by immunohistochemistry and compared with HER-2/neu expression within the same cancers. Results: Hsp-27 was overexpressed in 28 of 47 (60%) cases of DCIS; expression in pure DCIS was 16 of 24 (67%), and 12 of 23 (50%) in DCIS associated with IDC. Hsp-27 expression by in situ and invasive components of the same neoplasm were concordant in 22 of 23 (95%) cases tested. Comedo variants appeared to have somewhat higher hsp-27 expression than noncomedo DCIS, whether or not there was an associated IDC. These results are reminiscent of HER-2/neu oncoprotein expression in DCIS and DCIS associated with IDC observed by others. However, although 4 of 22 (18%) cancers containing DCIS + IDC expressed HER-2/neu, no relationship with hsp-27 expression in the same cancers was observed. Conclusions: We found a high incidence of hsp-27 overexpression in DCIS and in DCIS associated with IDC. This rate is twice that previously observed in IDC alone. Hsp-27 expression is independent of HER-2/neu expression.     

ER和PR及HER-2表达与乳腺癌分子分型及临床特征和预后的关系

目的:利用雌激素受体(ER)、孕激素受体(PR)及人表皮生长因子受体2(HER-2)的免疫组织化学检测结果将乳腺癌简易分为4种分子亚型,并探讨这4种分子亚型的临床特征和影响预后的相关因素。方法:根据ER、PR及HER-2的免疫组织化学检测结果,采用回顾性方法将本院收治的175例乳腺癌患者简易分为类luminal A型、类luminal B型、类HER-2(+)型及类basal-like型4种类型。对各型的临床特征采用SPSS17.0统计软件进行分析,并用Kaplan-Meier法和Cox回归分析各型乳腺癌患者的生存情况及预后因素。结果:在175例乳腺癌患者中,类luminal A型、类luminal B型、类HER-2(+)型及类basal-like型分别占56.00%(98/175)、17.71%(31/175)、12.57%(22/175)和13.71%(24/175)。类basal-like型与类luminal A型相比,患者无瘤生存率较低(P0.05)。经Cox多因素预后分析,淋巴结阳性患者的预后较淋巴结阴性患者差;类luminal A型患者预后最好,而类basal-like型患者预后最差。结论:淋巴结状况及分子分型是影响乳腺癌预后的重要因素。依据ER、PR及HER-2行乳腺癌分子分型与国际公认分型的临床表现及预后基本一致,对指导基层医院的乳腺癌预后及治疗同样具有重要意义。     

HER-2基因在胃癌中的检测与临床研究进展

曲妥珠单抗是人表皮生长因子-2(HER-2)的单克隆抗体.最新的研究发现,曲妥珠单抗联合化疗可明显改善HER-2阳性进展期胃癌患者的生存,但是目前胃癌HER-2基因的检测方法 如IHC、FISH等存在很多缺陷,一种新的自动化银增强染色(SISH)方法 有望成为胃癌HER-2检测的标准检测方法.本文对HER-2在胃癌中的...     

Intratumoral heterogeneity of HER2/neu in breast cancer--a rare event

HER2/neu is overexpressed in about 20% of invasive breast carcinomas. Numerous studies have shown that there is high level of concordance between the HER2/neu status of the primary breast cancer and the metastases of a given patient. Recently, changes in HER2/neu status with tumor progression have been reported, suggesting the possibility of an emerging different tumor clone. Little is known about intratumoral heterogeneity with regard to HER2/neu oncoprotein overexpression. We identified nine cases of invasive ductal carcinoma that showed intratumoral variation in HER2/neu oncoprotein expression by immunohistochemistry. This was confirmed by the intratumoral variation in the amplification status of the HER2/neu gene by fluorescence in situ hybridization and by chromogenic in situ hybridization. The results of this study suggest that some cases of primary breast carcinoma are heterogeneous in regard to HER2/neu gene amplification or protein overexpression. Heterogeneity of HER2/neu status in a tumor may be a rare event or underestimated. This phenomenon should be examined as it may contribute to a better understanding of the variation in therapeutic responses and the conflicting data in studies about the prognostic and predictive role of HER2/neu status in subsets of breast cancer patients.     

A study on the relationship between HER-2gene amplification and protein expression in invasive breast cancer

Objective To study the amplification and expression of HER-2 gene and protein in breast cancer and to investigate the relationship between HER-2 gene and Ki-67,P53,ER,PR,lymph node metastasis and TNM staging. Methods Fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) method were used to detect the amplification and expression     

23 COX-2和 HER-2在结直肠癌中的表达及其意义

为研究COX 2和HER 2在结直肠癌中的表达及其临床意义以及两者的相互关系，笔者采用免疫组化法检测123例结直肠腺癌及其中的25例淋巴结转移灶组织、12例远癌肠黏膜组织、15例结直肠腺瘤性息肉组织COX 2和HER 2的表达情况。结果示，COX 2在远癌组织、腺瘤性息肉、腺癌中的高表达率分别为0%，33.3％，81.3％，三者差异有统计学意义（P<0.001）;腺癌中COX 2的高表达与Dukes分期、淋巴结转移和浸润层次有关;HER 2的高表达在腺癌（67.5％）与腺瘤性息肉（80.0%）之间差异无统计学意义，但均高于远癌肠黏膜（33.3%）（P<0.05）;HER 2的胞膜高表达与浸润层次有关;在淋巴结转移灶中COX 2和HER 2具有相关性(χ2=3.949，P<0.05，c=0.3693）。提示 COX 2在正常组织、腺瘤性息肉及腺癌中的表达逐步上调;COX 2可能是结直肠癌发生的早期事件;COX 2的高表达及HER 2胞膜的高表达均与肿瘤侵袭性增高有关。     

Variation of the prognostic significance of HER-2 expression in breast cancer according to tumor size

The prognostic importance of HER-2 status in breast cancer has been investigated extensively, but findings have not been uniform across immunohistochemical studies using fixed, paraffin-embedded specimens. We speculate that studies with an overrepresentation of large tumors might not produce evidence for an independent effect of a single marker because breast tumors of larger size tend to exhibit multiple adverse attributes as the malignancy advances through the metastatic cascade. Further, it has been posited that results from certain studies of biologic markers might be generalizable only to larger tumors because tumor repositories tend to house a disproportionate number of larger tumors. To test our hypothesis that the prognostic effect of HER-2 status might be modified by the size of the tumor, we conducted a survival analysis of a nested case-case sample of 156 women diagnosed with primary breast cancer from 1983 to 1995. Relative risks (RRs) and confidence intervals (CIs) for recurrence in relation to HER-2 status were estimated using a multivariate Cox proportional hazards model. Immunohistochemistry of archival tissue was used to detect HER-2 expression. Positive HER-2 status was associated with recurrence (RR = 4.24, 95% CI 1.30-13.78) among patients with axillary lymph node-positive involvement. This analysis identified an interaction (p < 0.01) between tumor size and overexpression. Stratification by tumor size revealed an increased risk of recurrence associated with HER-2-positive tumors that were 相似文献   

The impact of HER-2 status on local recurrence in women with stage I-II breast cancer treated with breast-conserving therapy

This study was undertaken to determine whether overexpression of the oncogene HER-2 is associated with an increase in local recurrence in women with early stage breast cancer treated with breast-conserving therapy (BCT). A retrospective review of the medical records of all women treated with stage I-II invasive breast cancer from 1991 through 2001 was performed. Of 596 eligible patients treated in that time period, immunohistochemical testing for HER-2 expression was performed in 352 patients (59%): 266 patients (76%) were HER-2 negative and 86 patients (24%) were HER-2 positive. Median follow-up was 5.4 years. The patient characteristics for the two groups were compared for age, pathologic T and N stage, number of positive nodes, estrogen receptor (ER) and progesterone receptor (PR) status, radiation treatment, and use of hormonal therapy or chemotherapy. There were no significant differences in any of these parameters between the two groups (all p > or = 0.10). Local recurrence at 5 years was 2% in the HER-2-negative group and 0% in the HER-2-positive group (p = 0.15). There was no difference in local recurrence after BCT between HER-2-positive and negative breast cancers at 5 years. Therefore HER-2 overexpression does not appear to be a contraindication to BCT.     

乳腺癌钼靶X线钙化与HER-2/neu表达的关系及其意义

目的探讨乳腺癌钼靶X线钙化与HER-2／neu表达的关系及其临床意义。方法分析152例乳腺癌钼靶X线片的钙化特点；并将切除的肿瘤标本行HER-2／neu检测，分析钼靶X线钙化特征与HER-2／neu表达之间的关系。结果乳腺癌钼靶X线钙化组HER-2／neu过度表达率高于无钙化组（61．6％vs．35．4％）（P〈0．01）；在73例钙化中，以钙化伴随毛刺征为主要表现者，HER-2／neu过度表达率高于单纯钙化组（P〈0．05）。根据钙化形态特征，蠕虫状钙化组HER-2／neu过度表达率明显高于非蠕虫状钙化组（P=0．01）。钼靶X线钙化簇最大径≥25mm者，多在HER-2／neu过度表达组（P〈0．05），而钙化颗粒数≤20枚／cm^2者，多在HER-2／neu阴性表达组（P〈0．01）。结论乳腺癌钼靶X线钙化与HER-2／neu过度表达关系密切，可为乳腺癌治疗策略的制定和预测预后提供参考。志．2008．17（5）：436—439】     

The evolution in management of patients with subcentimeter,node-negative,triple-negative breast cancer

Background

The aim of this study was to determine the evolution in treatment recommendations and outcomes for patients with subcentimeter, node-negative, triple-negative disease.

Methods

Patients were divided into a remote (diagnosed from 1997 to 2003) and a recent (diagnosed from 2004 to 2011) group. Demographics, tumor size, surgical treatment, use of adjuvant chemotherapy, survival, and disease recurrence were evaluated.

Results

Thirty patients were placed in the remote group and 31 in the recent group. Demographics, tumor sizes, and surgical treatment were similar between groups. The use of adjuvant chemotherapy increased from 7% to 42% in the recent group (P < .002). Disease-free survival and recurrence (7%) was not influenced by the use of chemotherapy.

Conclusions

This study demonstrates that adjuvant chemotherapy is increasingly used in patients with the triple-negative phenotype, regardless of other favorable prognostic variables. The value of adjuvant chemotherapy for the subgroup of patients in our study is unclear and mandates further investigation.     

乳腺癌Her-2与TOP2A基因表达对新辅助化疗效果的预测价值

目的探讨乳腺癌HER 2及TOP2A基因的表达及其与蒽环类药物化疗效果的关系。方法收集我院4年间收治的新辅助化疗患者5 8例标本,采用FISH方法检测所有患者新辅助化疗前癌组织HER 2及TOP2A基因的表达情况;全组患者采用FEC方案行新辅助化疗。化疗4周期后按RECIST标准评估疗效;分析HER 2和TOP2A基因的扩增与疗效的关系。结果全组患者HER-2基因扩增19例(1 9/5 8,3 2.8%),TOP2A基因扩增1 1例(1 1/5 8,1 9.0%),HER 2与TOP2A共扩增1 1例(1 1/5 8,1 9.0%);HER-2基因、TOP2A基因及HER-2和TOP2A基因共扩增均与化疗效果呈正相关[rs=0.52(P0.0 5),rs=0.5 3(P0.0 5)及rs=0.5 6(P0.0 5)]。结论乳腺癌组织中HER 2及TOP2A的扩增均对蒽环类化疗药物的疗效有预测作用,两者的共扩增更有利于预测蒽环类药物的疗效。     

HER-2 gene amplification by chromogenic in situ hybridisation (CISH) compared with fluorescence in situ hybridisation (FISH) in breast cancer-A study of two hundred cases

The purpose of the study was to compare two methods used to analyse HER-2 gene amplification (fluorescence in situ hybridisation (FISH) and chromogenic in situ hybridisation (CISH)), and determine the accuracy of the antibodies CB11 and HercepTest for immunohistochemical detection of HER-2 overexpression from archival breast cancer tissue. Additionally, interobserver variability in the interpretation of CISH and immunohistochemical tests was measured. Two hundred cases of invasive breast carcinoma diagnosed between 2000 and 2003 were selected. Immunohistochemistry (IHC) was performed with HercepTest and CB11, and gene amplification was determined by FISH (PathVision, Vysis) and CISH (Zymed) using tissue macroarrays. An excellent concordance (94.8%) was found between CISH and FISH. Considering FISH as gold standard, sensitivity of CISH was 97.5% and specificity 94%. Overall interobserver agreement of CISH was 97.5% and of IHC 84%. Both antibodies showed a sensitivity of 95.2% and a specificity of 70.7% (CB11) and 81.2% (HercepTest). Our results show that CISH is a highly accurate, reproducible and practical technique to determine HER-2 gene amplification. CB11 and HercepTest are good screening methods with a high sensitivity. The performance of tissue macroarrays to test HER-2 status by IHC, FISH and CISH has demonstrated to be an available and effective method to study large series of tumours.     

Elevated levels of chemokine receptor CXCR4 in HER-2 negative breast cancer specimens predict recurrence

INTRODUCTION: CXCR4 is a chemokine receptor that has recently been implicated to play a pivotal role in breast cancer growth and metastasis. In animal models, reduction of CXCR4 expression significantly abrogated metastatic disease and prolonged survival. In human breast cancers, CXCR4 overexpression may portend a worse clinical course. Recent data suggest that HER-2 up-regulates CXCR4, but whether this is applicable in the clinical setting is not known. In this study, we evaluated the role of CXCR4 overexpression in breast cancer and determined whether it can serve as a potential marker of tumor recurrence in HER-2 negative tumors. METHODS: One hundred three patients with stages I to III breast cancers and 6 benign breast tissues were prospectively accrued and analyzed. Study homogeneity was maintained by standardized treatment, surveillance, and compliance protocols. CXCR4 levels were detected using Western blots and results were quantified against 1 microg of HeLa cells (positive controls). HER-2 expression was evaluated using the Hercep program, (Dako Corp., Carpinteria, CA) with a positive result defined as > or = 2. CXCR4 expression was defined as low (<6.6-fold) or high (> or = 6.6-fold). Primary endpoints were cancer recurrence and death. Statistical analysis performed included Spearman's correlation, independent samples t-test, Kaplan-Meier survival analysis, and log-rank test. RESULTS: All 103 cancer specimens had CXCR4 overexpression (mean 6.6 +/- 4.7), while none of the 6 benign breast tissues had detectable level of CXCR4. There were 36 HER-2 (+) tumors and 67 HER-2 (-) tumors. There was no statistical significance in mean CXCR4 overexpression between HER-2 (+) [5.6] and HER-2 (-) [6.6] cancers (P = 0.3; independent samples t-test). Recurrences occurred in 18 of 103 patients (17%); 10 occurred in HER-2 (+) tumors, and 8 occurred in HER-2 (-) patients. CXCR4 expression level was not predictive of cancer recurrence (P = 0.80) or overall survival (P = 0.70) in the HER-2 (+) group. However, among HER-2 negative tumors, 7 of 8 recurrences occurred in the high CXCR4 group (P = 0.037). There was no correlation between the degree of CXCR4 overexpression with tumor size (r = 0.13, P = 0.22), nodal status (r = 0.019, P = 0.4), ER/PR status (r = 0.12, P = 0.29), and HER-2 status (r = 0.091, P = 0.36). CONCLUSIONS: CXCR4 overexpression was observed in all 103 breast cancer specimens but was undetectable in benign breast tissues. CXCR4 overexpression does not correlate with tumor size, nodal status, ER/PR status, and HER-2 status. High CXCR4 overexpression had a significant impact on disease-free survival in HER-2 negative breast cancer patients and may help identify a subset of HER-2 negative breast cancers that have a more aggressive biological behavior.