A Comprehensive Model for Predicting Recurrence and Survival in Cases of Chinese Postoperative Invasive Breast Cancer

We investigated relationships between clinical pathologic data, molecular biomarkers and prognosis of invasive breast cancer based on a Chinese population. Immunohistochemistry (IHC) was used to assess the status of ER, PR, HER-2 and Ki-67, with fluorescence in situ hybridization (FISH) performed to further confirm HER-2 positivity with an equivocal result (IHC 2+). Subsequently, Kaplan-Meier univariate and multivariate COX regression analyses of ER, PR, HER-2, Ki-67, clinical features, therapeutic status and follow-up data were performed according to the establishment principle of the Nottingham prognostic index (NPI). From this study, age, tumor size, lymph node status, ER, HER-2, Ki-67 status were found to be associated with prognosis. Eventually, a prognostic model of (PI= (1.5×age) - size + (0.1×lymph node status) - (0.5×ER) + (2×HER-2) - (0.2×Ki-67)) was established with 288 randomly selected patients and verified with another 100 cases with invasive breast cancer. Pearson correlation analysis demonstrated a significant positive correlation index of 0.376 (P=0.012<0.05) between the prognostic index (PI) and actual prognosis. Remarkably, the consistency with the model predicted recurrence was 93% in the validation set. Therefore, it appears feasible to predict the prognosis of individuals with invasive breast cancer and to determine optimal therapeutic strategy with this model.     

74例三阴性乳腺癌临床特征及预后分析

[目的]探讨三阴性乳腺癌的临床病理特征、复发及预后。[方法]回顾性分析2000年7月至2006年7月手术治疗的486例乳腺癌患者资料。将ER、PR、HER-2均为阴性患者定义为三阴性乳腺癌组,其他患者定义为非三阴性乳腺癌组。采用免疫组化法检测ER、PR、HER-2的表达,随访观察患者的生存情况。74例(15.2%)符合三阴性乳腺癌诊断标准。[结果]与非三阴性乳腺癌组比较,三阴性乳腺癌组绝经前患者比例升高,组织学分级较高。三阴性乳腺癌组5年无病生存率、5年总生存率均低于非三阴性乳腺癌组(P=0.038,P=0.014)。且三阴性乳腺癌患者更容易出现内脏转移(P=0.024),复发后生存时间更短(P=0.000)。[结论]三阴性乳腺癌患者有着特殊的临床病理特征,易出现复发转移(尤其是内脏转移),预后差。     

乳腺癌组织中ER、PR、cerbB-2、Ki-67表达及其意义

目的探讨乳腺癌组织中雌激素受体（ER）、孕激素受体（PR）、cerbB-2和Ki-67基因的表达及其临床意义。方法采用S-P免疫组化方法,检测107例乳腺癌组织中ER、PR、cerbB-2、Ki-67的表达水平,并结合其患者的相关临床资料进行分析。结果乳腺癌组织中ER、PR、cerbB-2、Ki-67阳性表达率分别为56.1%、82.2%、71.0%、67.3%。ER、PR、cerbB-2、Ki-67阳性表达与乳腺癌腋窝淋巴结转移和临床分期显著相关（P〈0.05）。而与患者年龄、肿瘤大小无相关性（P〉0.05）。相关分析结果显示ER与PR表达呈正相关（P=0.000）,与Ki-67表达呈负相关（P=0.000）;PR与cerbB-2、Ki-67表达呈负相关（P=0.012、0.006）。结论 ER、PR和cerbB-2、Ki-67与乳腺癌的发生、发展有关,联合检测ER、PR、cerbB-2和Ki-67,有助于客观评估乳腺癌的生物学行为,从而指导临床治疗和预后判断。     

Immunohistochemical Evaluation of Ki-67 and Comparison with Clinicopathologic Factors in Breast Carcinomas

Background: Patients primarily received tamoxifen based on their menopausal status due to the lack ofimmunohistochemistry. A recent study has shown that hormonal receptors were not correlated with menopausal status,and thus, indicating that they present limited therapeutic and prognostic significance in breast cancer management.This study aimed to evaluate Ki-67 value and analyze its association with clinicopathologic parameters in breast cancerpatients. Methods: The formalin-fixed paraffin-embedded breast tissue blocks of 125 patients with primary breastcarcinomas were subjected to immunohistochemical analysis using Ventana Benchmark® GX automated immunostainer.Analysis of variance and Chi-2 test were used to examine the relationship between Ki-67 and clinicopathologicvariables. Results: The mean age of 125 patients included in the study was 47.7 years. The average score of Ki-67was 56.0%. 84.8% of patients showed Ki-67 ≥ 14%. Mean scores of Ki-67 were correlated with grade (p = 0.006),PR (p = 0.026), histological type, ER, combined ER/RP, and molecular subtype (p < 0.001). Ki-67 was independentof HER2 (p = 0.402) and menopausal status (p = 0.471). The frequency of Ki-67 according to St Gallen 2011 wasassociated with histological type (p = 0.005), grade (p = 0.005), ER (p < 0.001), combined ER/PR (p = 0.004), andmolecular subtype (p = 0.004). There was no significant relationship between the distribution of Ki-67 and the age ofthe patients (p = 0.859), menopausal status (p = 0.979), PR (p = 0.149), and HER2 (p = 0.597). Conclusion: Ki-67 isuseful for treatment decisions in primary breast cancer patients. The high value of Ki-67 was associated with adverseclinicopathologic factors. The increased Ki-67 value should be carefully investigated in triple negative patients.     

乳腺癌生物标志物表达状态的时间变异性

目的 探讨乳腺癌患者复发前后HER-2和激素受体表达是否存在时间变异性。方法 收集168例长期随访（>5年）的乳腺癌患者不同时间点的组织标本,并通过免疫组织化学进行HER-2、ER和PR检测,比较不同时间点上述生物标志的差异,同时分析与患者原始治疗和复发后治疗的关系。结果 168例乳腺癌患者中,36例复发,对其中27例复发组织标本进行检测。发现5例患者出现HER-2表达状态的变化,其中3例HER-2下调,2例上调;7例出现ER变化：5例ER表达下调,2例ER表达上调。2例出现PR下调。HER-2的表达变化与复发前放化疗无明显联系,但抗激素治疗导致HR表达下调,激素受体变化对随后的化疗治疗效果稍差（76% vs. 88%,P=0.21）,无疾病进展时间相似（33.4月vs. 38.60月,Log-rank=1.96,P=0.16）。结论 乳腺癌患者HER-2和激素受体的表达可以随时间变异,复发患者需要再次检测上述生物标志。     

Ki67 Index in Breast Cancer: Correlation with Other Prognostic Markers and Potential in Pakistani Patients

Introduction: Breast cancer aggressiveness can be correlated with proliferation status of tumor cells, whichcan be ascertained with tumor grade and Ki67 indexing. However due to lack of reproducibility, the ASCO donot recommend routine use of Ki67 in determining prognosis in newly diagnosed breast cancers. We thereforeaimed to determine associations of the Ki67 index with other prognostic markers like tumor size, grade, lymphnode metastasis, ER, PR and HER2neu status. Methods: A total of 194 cases of newly diagnosed breast cancerwere included in the study. Immunohistochemical staining for ER, PR, HER2neu and Ki67 was performed bythe DAKO envision method. Associations of the Ki67 index with other prognostic factors were evaluated bothas continuous and categorical variables. Results: Mean age of the patients was 51.7 years (24-90). Mean Ki67index was 26.9% (1-90). ER, PR, HER2neu positivity was noted in 90/194 cases (46.4%), 74/194 cases (38.1%)and 110/194 cases (56.70%) respectively. Significant association was found between Ki67 and tumor grade,PR, HER2neu positivity and lymph node status, but no link was apparent with ER positivity and tumor size.There wasan inverse relation between Ki67 index and PR positivity, whereas a direct correlation was seen withHER2neu positivity. However, high Ki67 (>30%) was associated with decreased HER2neu positivity as comparedto intermediate Ki67 (16-30%). The same trend was established with lymph node metastasis. Conclusion: Ourstudy indicates that with high grade tumors, clinical utility of ki67 is greater in combination with other prognosticmarkers because we found that tumors with Ki67 higher than 30% have better prognostic profile comparedto tumors with intermediate Ki67 level, as reflected by slightly lower frequency of lymph node metastasis andHER2neu expression. Therefore we suggest that Ki67 index should be categorized into high, intermediate andlow groups when considering adjuvant chemotherapy and prognostic stratification.     

青年乳腺癌雌激素受体与Ki-67关系的研究

目的 研究青年乳腺癌雌激素受体表达与Ki-67指数的关系.方法 采用免疫组化S-P法,用抗ER、Ki-67单克隆抗体,研究32例青年乳腺癌和36例绝经后乳腺癌ER与Ki-67的表达.结果 青年乳腺癌17例(53.13%)ER阳性,绝经后乳腺癌20例(55.56%)ER阳性;青年乳腺癌ER阳性组Ki-67指数明显高于绝经后乳腺癌阳性组,差异有统计学意义(P＜0.01);而两者ER阴性组差异无统计学意义(P＞0.05).结论 青年乳腺癌ER阳性组肿瘤细胞增殖活性明显高于绝经后乳腺癌ER阳性组,这是青年乳腺癌恶性度高的重要原因.     

乳腺癌组织中PPARγ与内分泌治疗预测指标相关性

[目的]研究乳腺癌组织中过氧化物酶增殖激活受体γ(peroxisome proliferator activated receptors γ,PPARγ)的表达与ER、PR、pS2、C-erbB-2之间的关系,探讨其临床意义。[方法]应用组织芯片和免疫组织化学EnVision法检测71例乳腺癌组织和41例非癌组织PPARγ、ER、PR、pS2、C-erbB-2的表达。[结果](1)71例乳腺癌中PPARγ、ER、PR、pS2和C-erbB-2的阳性表达率分别为47.89%、64.79%、61.97%、39.44%和40.85%。(2)PPARγ的表达与组织学分级呈正相关(P<0.01)。(3)PPARγ的表达与ER、PR表达分别呈正相关(C1=0.3102,C2=0.2441),与pS2、C-erbB-2的表达无显著性相关(P>0.05)。[结论]PPARγ在分化较好和ER阳性乳腺癌中高表达,与ER、PR、pS2、C-erbB-2联合检测有助于指导内分泌治疗及评估预后。     

Prognostic Factors of Locally Advanced Breast Cancer PatientsReceiving Neoadjuvant and Adjuvant Chemotherapy

Background: Neoadjuvant chemotherapy is known to be beneficial for down-staging patients with locallyadvanced breast cancer. Clinical stage, degree of cell differentiation and expression of estrogen/progesteronereceptors and HER2/neu are all prognostic factors that may effect survival of patients with locally advancedbreast cancer. The present study was conducted to determine their influence in a series of Indonesian patientsMaterials and Methods: The subjects were a total of 52 patients with locally advanced breast cancer in SardjitoGeneral Hospital Yogyakarta, from January 2003 to June 2006. Survival analysis with Kaplan Meier was testedfor age, clinical stage, degree of histological differentiation, estrogen-progesterone receptor (ER/PR), HER-2expression and neoadjuvant as well as adjuvant chemotherapy. To find the most important influencing factors,significant variables were tested with multivariate Cox regression. Result: Of the 52 patients with locallyadvanced breast cancer, most were between 40-60 years old (41, 78%), almost half were stage IIIA (23 ,44%),and the majority were negative for ER and PR (32, 61%). Her2 positivity was found in 29 patients (55%) and amoderate histological grade in 26 (50%). Thirty-nine patients were alive at the end of the study period (75%).There were no significant differences in survival between patients with and without adjuvant and neoadjuvantchemotherapy. Tumor characteristics that did influence survival were advanced stage (p<0.001) and histologicalgrade (p<0.001), while HER-2 and ER/PR hormonal status had no effect. Conclusion: Clinical stage and degreeof histological grade are the most significant prognostic factors for Indonesian locally advanced breast cancercases, while hormonal status and HER-2 did not appear impact on our patient’s survival.     

HER-2/neu Status: A Neglected Marker of Prognostication and Management of Breast Cancer Patients in India

Background: Categorizing breast tumors based on the ER, PR and HER/Neu 2 receptor status is necessary in order to predict outcome and assist in management of breast cancer. Herfe we assessed this question in South Indian patients. Materials and Methods: A total of 619 formalin fixed paraffin embedded breast tumor tissues were collected from pathology archives after receipt of ethical clearance. With the help of primary and secondary conjugated antibodies, expression status of ER, PR and HER2/neu was determined. All the experimental data were assessed for correlations with histopathological features of tumors and clinical presentation of the subjects. Results: In the present study, the ages ranged from 20-87 years with a mean of 50.0±12.q years, and majority of the tumors (84%) were of infiltrating duct cell carcinoma type. Assessment of ER, PR and Her-2/neu expression showed that 46% were triple negative. Interestingly, an inverse relation between ER, PR and HER-2/neu was apparent in 41.2% (p<0.0001) of the tumors, of which 24.5% (p<0.0001) were ER and PR co-negative but HER-2 positive. Conclusions: ER and PR positive tumors are less common (i.e<30%) compared to HER-2/neu positive tumors (i.e>50%) in Indian breast cancer patients, underlining the need for effective diagnostic screening and specific therapeutic managements in order to improve the survival rate of patients in low resource countries such as India.     

ER、PR与C-erbB-2、Ki-67在乳腺癌中的表达及其临床意义

目的 探讨乳腺癌组织中ER、PR与C-erbB-2、Ki-67的表达及它们的相关性.方法 采用免疫组化检测,对356例乳腺癌患者ER、PR、C-erbB-2及Ki-67的表达、临床病理特征以及它们的相关性进行回顾性分析.结果 ER、PR、C-erbB-2及Ki-67的表达与淋巴结转移相关(P<0.05);乳腺癌组织分级...     

新辅助化疗对乳腺癌ER、PR和EphA2表达的影响及意义

目的研究乳腺癌中ER、PR和EphA2的表达在新辅助化疗前后的变化及临床意义。方法采用免疫组织化学SP法检测新辅助化疗前后ER、PR和EphA2在52例乳腺癌的表达情况。结果ER、PR和EphA2的表达均与疗效相关;新辅助化疗后EphA2的阳性表达率显著下降（P＜0.05）;ER、PR的阳性表达率则无明显变化（P＞0.05）。结论新辅助化疗能抑制肿瘤细胞增殖,促进肿瘤细胞凋亡,显著降低EphA2的阳性表达,而对ER、PR的表达无显著影响。     

Expression of ER,PR, and Her-2/neu in Endometrial Cancer: A Clinicopathological Study

Objective: To determine any association between expression of estrogen receptor (ER), progesterone receptor(PR), and Her-2/neu and clinicopathological features, including survival, of endometrial carcinoma (EMC)patients. Methods: Samples of formalin-fixed, paraffin-embedded tissue of 108 patients with EMC treated atour institution between January 1994 and December 2007 were immunohistochemically studied. Results: ER,PR, and Her-2/neu expression were positive in 59.3%, 65.7% and 2.8% of cases, respectively. Positive ERexpression was significantly associated with grade I-II tumor while PR expression was linked with endometrioidhistology, grade I-II tumor, less myometrial invasion (MI) and negative lymph node involvement. Her-2/neuexpression was significantly associated with deep MI, while positive ER and negative Her-2/neu expression incombination was significantly associated with longer disease-free and overall survival. Conclusion: ER expressionis a good prognostic factor while Her-2/neu expression appears to be a poor indicator for both disease-free andoverall survival, while PR tended to show favorable influence for only disease-free survival of Thai EMCs.     

ER阳性细胞比率对乳腺癌Her-2基因状态的预测作用

[目的]通过研究Her-2免疫组化检测结果为不确定(2+)的乳腺癌患者的临床病理特征,寻找预测Her-2基因状态的方法。[方法]纳入51例Her-2免疫组化检测结果为2+的乳腺癌患者,采用荧光原位杂交法(FISH)确定其Her-2基因状态,比较Her-2基因扩增组与未扩增组之间的临床病理特征,通过组间差异寻找预测Her-2基因状态的指标。[结果]51例患者中,FISH检测Her-2基因未扩增者25例,扩增者26例。Her-2基因未扩增组与扩增组间患者的年龄、肿瘤大小、淋巴结状态、TNM分期、PR状态差异无统计学意义,ER状态差异有统计学意义。ER阳性率与Her-2基因扩增呈负相关。ER阳性细胞比>75%的患者主要(83.3%,15/18)存在于Her-2基因未扩增组中,ER阳性细胞比≤75%的患者主要(69.7%,23/33)存在于Her-2基因扩增组中。[结论]对Her-2免疫组化检测结果为2+的乳腺癌患者中,ER阳性细胞比率可粗略预测Her-2基因的状态。     

激素受体和HER-2及Ki-67预NSL腺癌新辅助化疗疗效价值的分析

目的：探讨乳腺癌组织中雌激素受体（ER）、孕激素受体（PR）、人表皮生长因子受体2（HER-2）及Ki-67的表达状态对新辅助化疗反应的预测作用以及化疗前后其表达差异对疗效的影响。方法：免疫组织化学方法检测新辅助化疗前后118例乳腺癌组织的ER、PR、HER-2及Ki-67的表达情况,并分析其与新辅助化疗疗效的关系。结果：118例新辅助化疗乳腺癌病例中,ER-和PR-组pCR分别为26．1％和27．1％,明显高于ER＋组11．1％和PR＋组6．8％,P-0．003。HER-2和Ki-67的表达对新辅助化疗疗效无显著影响。新辅助化疗前ER、PR与Ki-67的表达呈明显负相关,P〈0．001;新辅助化疗后Ki-67的高表达病例数显著减少,P-0．001。结论：ER-／PR-的患者对新辅助化疗更为敏感,Ki-67在化疗后发生了显著下调,提示新辅助化疗能降低肿瘤的增殖活性。ER、PR及Ki-67可以作为新辅助化疗疗效的预测指标。     

乳腺癌复发及转移灶分子生物学指标的变化

目的:探讨分析复发转移性乳腺癌患者中原发灶和复发转移灶的肿瘤组织ER、PR、Her-2、Ki67及p53免疫组化表达变化规律及特征.方法:选取我院66例复发转移性乳腺癌患者,分别分析原发灶和复发灶、原发灶和转移灶的肿瘤组织ER、PR、Her-2、Ki67及p53免疫组化表达情况.结果:在原位复发性乳腺癌复发前后表达变化差异经x2检验后提示ER:P =0.615;PR:P =0.497;Her-2:P =0.562;Ki67:P =0.001;p53:P =0.394,仅Ki67表达在原发灶和复发灶之间的变化有统计学意义(P＜0.05).在转移性乳腺癌复发前后表达变化差异经x2检验后提示ER:P=0.711;PR:P =0.538;Her-2:P =0.664;Ki67:P=0.001;p53:P=0.447,仅Ki67表达在原发灶和转移灶之间的变化有统计学意义(P＜0.05).同时得出,复发性和转移性乳腺癌组织中由阳性转阴性比率均高于由阴性转阳性.ER、PR、Her-2、p53在复发性和转移性乳腺癌复发前后表达差异无统计学意义(P＞0.05).结论:复发转移性乳腺癌组织Ki67的变化主要为表达呈衰减趋势(复发转移前的高表达转为复发转移后的低表达),仅Ki67表达在原发灶和转移灶之间的变化有统计学意义,表明Ki67是一项敏感指标,对预测化疗效果有重要的指导意义.ER、PR、Her-2、p53的改变无统计学意义,但是也存在部分病例发生变化,应需对该类病例讨论或修订其后续治疗方案.     

新辅助化疗对乳腺癌疗效和雌激素受体孕激素受体Ki-67和人表皮生长因子受体2表达的影响分析

目的了解新辅助化疗（NAC）在局部进展期乳腺癌治疗前后ER、PR、Ki-67及HER-2的变化,探讨其与新辅助化疗疗效之间的相关关系。方法 46例接受新辅助化疗的乳腺癌患者纳入研究,分析患者术前弹射式空芯针穿刺活检标本和术后大标本癌组织ER、PR、Ki-67和HER-2表达的变化。患者化疗前行乳腺肿瘤粗针穿刺活检并免疫组化方法检测肿瘤组织ER、PR、Ki-67和HER-2的表达。化疗后评估疗效并对接受手术的患者的手术标本通过同法检测各指标的表达。结果新辅助化疗前后ER、PR、Ki-67和HER-2的表达均发生了改变,新辅助化疗前ER、PR、Ki-67和HER-2阳性表达的肿瘤组织新辅助化疗后下调（ER：82.6%和80.4%;PR：78.3%和71.7%;Ki-67：39.1%和30.4%;HER-2：28.3%和26.1%）,但没有统计学意义（P〉0.05）。ER、PR、Ki-67和HER-2阳性表达疗效有效率与阴性表达有效率分别为ER：68.4%和50.0%;PR：66.7%和60.0%;Ki-67：77.8%和57.1%;HER-2：53.8%和69.7%。ER、PR、Ki-67、HER-2表达状态与化疗效果均无明显的关系（均P〉0.05）。结论新辅助化疗可以改变ER、PR、Ki-67和HER-2的表达,本临床研究未发现ER、PR、Ki-67和HER-2的变化与局部进展期乳腺癌的新辅助化疗疗效有相关关系。     

南阳地区妇女三阴乳腺癌临床特征及预后分析

目的 探讨南阳地区妇女三阴乳腺癌临床特征及预后.方法 回顾性分析218例确诊并且行手术切除治疗的南阳地区妇女乳腺癌患者临床资料,按照免疫组织化学检测雌激素受体(ER)、孕激素受体(PR)、人表皮生长因子受体2(Her-2)均为阴性者共63例为三阴组,ER、PR、Her-2有一项或多项阳性者共155例为非三阴组,分析2组临床特征及预后.结果 三阴组患者平均年龄、未绝经患者、病理分级Ⅲ级、TNM分期T3、腋淋巴结转移阳性、病理类型为浸润性导管癌、肿瘤直径≥5 cm者所占比例明显高于非三阴组(P＜0.05).三阴组患者5年复发率41.27％、转移率34.92％,非三阴组5年复发率22.58％、转移率20.00％;三阴组淋巴结转移率、内脏转移率、骨转移率、脑转移率分别为12.70％、28.57％、15.87％、22.22％,非三阴组为6.45％、14.19％、12.26％、11.61％,2组差异有统计学意义(P＜0.05).三阴组3年、5年无瘤生存率为42.86％、23.81％,总生存率为85.71％、66.67％;非三阴组3年、5年无瘤生存率为63.23％、43.87％,总生存率为94.19％、81.94％.3年、5年无瘤生存率及总生存率三阴组均低于非三阴组(P＜0.05).结论 南阳地区妇女三阴乳腺癌具有发病早、组织学分级高、浸润性强的特点,术后更容易发生复发及转移,预后较差.     

TIMAP Upregulation Correlates Negatively with Survival in HER2- Negative Subtypes of Breast Cancer

Objective: TIMAP expression is regulated by transforming growth factor beta 1 (TGFβ1); known for its role in breast cancer development and metastasis. Nevertheless, data on TIMAP protein expression and its association with breast cancer development are lacking. In this study, we aimed to investigate the variation in TIMAP protein expression in breast cancer tissue and its correlation with various clinicopathological characteristics of breast cancer patients and overall survival rate. Methods: A total of 159 paraffin-embedded tissue blocks from women diagnosed with four breast cancer subtypes (49 HER2-only, 33 Luminal A, 39 Luminal B, and 38 triple negative) were used to construct tissue microarray (TMA), followed by TIMAP immunohistochemistry (IHC). TIMAP expression was scored by two pathologists and categorized as weak (1-33% expression), moderate (34-66%), and strong (67-100%). Chi-square test and Kaplan Meier survival test were performed to determine the association between TIMAP expression and clinicopathological features and overall survival rate, respectively. Results: TIMAP protein was strongly expressed in 46 (93.9%) HER2-only, 32 (97%) luminal A, 37 (94.9%) luminal B, and 29 (76.3%) triple negative. TIMAP expression negatively associated with ER/PR expression (P=0.03), and it negatively impacted the overall survival in HER2 negative group (P=0.02). Conclusion: Our findings suggest that TIMAP protein expression is upregulated in all breast cancer subtypes. However, its prognostic role is exclusively observed in HER2- negative group, suggesting a potential of targeting TIMAP in future therapeutic strategies in this group.     

Prognostic Significance of Tumor Cell Proliferation Analyzed in Fine Needle Aspirates from Primary Breast Cancer

The objective of this study was to analyze the role of proliferating fraction (PF) measured with Ki-67/MIB-1 antibody in a large series of preoperative fine-needle aspirate (FNA) biopsies as a prognosticator of disease recurrence. The study comprised 732 patients who all had a conclusive cytological diagnosis of breast cancer. The follow-up time ranged from 1.2 to 10.2 years with a median of 5.7 years. In multivariate analysis Ki-67/MIB-1 value was a strong (p<0.001) significant, prognosticator of disease recurrence free interval (DRFI) independent of lymph node status, progesterone receptor content, and tumor size. In the subgroup analysis of 430 node-negative patients the distant recurrence-free rate after 5 years was 94.4% in patients with Ki-67/MIB-1 value<15% compared to 88.7% in patients with Ki-67/MIB-1 value 15% (p=0.03). Test of the interaction between tumor size and the value of PF revealed a p-value of 0.06. If the patients, in addition, had a tumor size 20mm the distant recurrence-free rate after 5 years was 93.2% if Ki-67/MIB-1<15% compared to 80.7% in patients with Ki-67/MIB-1 value 15%. This difference was statistically significant (p<0.01). For patients with tumors <20mm Ki-67/MIB-1 value did not add any prognostic information. In the subgroup of 302 node-positive patients the distant recurrence-free rate after 5years was 86.0% in patients with Ki-67/MIB-1 value<15% compared to 70.6% in patients with Ki-67/MIB-1 value 15% (p<0.01). We conclude that PF assessed by Ki-67/MIB-1 antibodies in preoperative FNA biopsies has a significant prognostic value independent of lymph node status, PgR status and tumor size. To our knowledge, this is the first study demonstrating PF, which can contribute prognostic information when analyzed in preoperative smears.