Tumor Mutation Burden Prediction Model in Egyptian Breast Cancer patients based on Next Generation Sequencing

Objectives: This study aimed to identify the tumor mutation burden (TMB) value in Egyptian breast cancer (BC) patients. Moreover, to find the best TMB prediction model based on the expression of estrogen (ER), progesterone (PR), human epidermal growth factor receptor 2 (HER-2), and proliferation index Ki-67. Methods: The Ion AmpliSeq Comprehensive Cancer Panel was used to determine TMB value of 58 Egyptian BC tumor tissues. Different machine learning models were used to select the optimal classification model for prediction of TMB level according to patient’s receptor status. Results: The measured TMB value was between 0 and 8.12/Mb. Positive expression of ER and PR was significantly associated with TMB ≤ 1.25 [(OR =0.35, 95% CI: 0.04–2.98), (OR = 0.17, 95% CI= 0.02-0.44)] respectively. Ki-67 expression positive was significantly associated with TMB >1.25 than those who were Ki-67 expression negative (OR = 9.33, 95% CI= 2.07-42.18). However, no significant differences were observed between HER2 positive and HER2 negative groups. The optimized logistic regression model was TMB = -27.5 -1.82 ER – 0.73 PR + 0.826 HER2 + 2.08 Ki-67. Conclusion: Our findings revealed that TMB value can be predicted based on the expression level of ER, PR, HER-2, and Ki-67.     

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。     

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.     

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。     

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.     

Impact of Her-2 Overexpression on Survival of Patients with Metastatic Breast Cancer

Introduction: Breast cancer is a complex and heterogeneous disease which is increasingly important as a public health problem. In Brazil, 57,960 new cases have been estimated to be the burden in 2016 and 2017. Despite advances in early diagnosis and therapy, approximately 20-30% of patients, even with early stage lesions, will develop distant metastatic disease. Tumors with similar clinical and pathological presentations may have differing behavior, so it is important to understand specific biological characteristics. Objective: To investigate tumor markers of primary tumors featuring pleural metastasis to identify organ-specific characteristics of metastatic breast cancer. Methods: In a historical cohort study, immunohistochemistry was performed on cell blocks of neoplastic pleural effusions and results were compared with clinicopathological data. Results: The median survival time with Her-2 overexpression in malignant pleural effusions was 2.2 months, whereas cases without overexpression survived, on average, for seven months (p = 0.02). Conclusions: We emphasize that metastases may behave independently of primary tumors, but the present results indicate that therapeutic agents targeting Her-2 overexpression could increase survival in metastatic breast cancer cases.     

分子分型在乳腺癌术后复发转移中的应用研究

[目的]研究乳腺癌分子分型与术后复发转移的关系。[方法]收集术后复发转移的乳腺癌患者的临床病理资料,明确患者复发转移的部位及时间,分析各分子亚型与临床病理特征以及复发转移部位、时间的关系。[结果]入组299例术后复发转移的乳腺癌患者,其中Luminal A型、Luminal B型、Her-2阳性型和Basal-like型分别为92例、79例、47例和81例。各分子亚型中年龄（P=0.034）、月经状况（P=0.013）、肿瘤组织学分级（P=0.000）、术后淋巴结转移情况（P=0.035）、术后复发转移时间（P=0.000）以及术后复发转移部位（P=0.007）存在显著差异。Cox逐步回归分析显示,组织学分级（P=0.000）和分子分型（P=0.000）是乳腺癌术后复发转移的独立预后因子。[结论]乳腺癌分子分型作为传统TNM分期的重要补充,能够很好地预测乳腺癌术后复发转移部位和时间,有助于临床医师对术后患者进行个体化随访筛查。     

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.     

预测M0期炎性乳腺癌术后生存的新N分期系统

目的 结合转移淋巴结数目和转移淋巴结比率,为术后M0期的炎性乳腺癌患者建立新的N分期系统。方法 基于SEER数据库中的炎性乳腺癌患者数据,计算出转移淋巴结数目和转移淋巴结比率的最佳截断值,形成新N分期系统。将新N分期系统与美国癌症联合会制定的第8版乳腺癌TNM分期系统进行比较,构建列线图预后模型并加以验证。结果 新N分期系统对M0期炎性乳腺癌患者术后生存的预测性能优于传统N分期系统。列线图预后模型显示出优秀的临床效能,一致性指数达0.711。结论 新N分期系统对M0期炎性乳腺癌患者的术后生存具有良好的预测性能,能更加精准地反映预后。     

Clinico-Pathologic Subtypes of Breast Cancer Primary Tumors Are Related to Prognosis after Recurrence

Background: Pathological factors, based mainly on immunohistochemistry (IHC) and histological differentiation, are mostly used to differentiate breast cancer (BC) subtypes. Our present aim was to describe the characteristics and survival of a relapsing BC patient cohort based on clinico-pathologic subtypes determined for the primary tumors. Methods: We used a clinico- pathological definition of BC subtypes based on histological grade (HG), estrogen receptor (ER), progesterone receptor (PgR),and epidermal growth factor receptor type 2 (HER2) expression assessed by IHC. We determined variables associated with loco-regional recurrence (LRR), second primaries (SP), systemic recurrence (SR) and post-recurrence survival (PRS). Results: Out of 1,702 patients, 240 (14%) had an event defined as recurrence. Those with recurrent disease were significantly younger than those without,and were initially diagnosed at more advanced stages, with larger tumors, greater lymph nodal involvement and higher HG. With a median follow up of 61 months (1-250), 4.6% of patients without recurrence and 56.6% of patients with an event defined as recurrence had died. The median PRS for the LRR group was 77 months; 75 months for those who developed a SP and 22 months for patients with an SR (p <0.0001). In SR cases, the median PRS was shorter for ER- tumors than for ER+ tumors (15 vs. 26 months, respectively; p = 0.0019, HR 0.44; CI: 0.25-0.44). Conclusions: Subtype, defined through classic histopathologic parameters determined for primary tumors, was found to eb related to type of recurrence and also to prognosis after relapse.     

男性乳腺癌34例生存分析

目的：探讨男性乳腺癌的生物学特性、治疗及预后情况.方法：对1980年3月～2005年3月吉林大学第一医院收治的34例男性乳腺癌患者的临床资料进行回顾性分析,采用Kaplan-Meier法计算生存率、绘制生存曲线.结果：pTNM分期Ⅰ期6例,Ⅱ期24例,Ⅲ期4例,腋窝淋巴结转移率35.3%（12/34）.均采用改良根治术,术后复发率11.8%（4/34）.5年生存率65.3%.结论：与女性乳腺癌相比,男性乳腺癌有其独特的生物学特性,治疗上采用以手术为主的综合治疗.肿瘤分期和激素受体表达等因素是影响预后的主要因素.     

Association of Proliferative Activity in Invasive Ductal Carcinoma Breast in Pakistani Population

Background: Personalized medicine has played very important role in management of breast cancer.  Proliferative index is one among the prognostic and predictive factor but unfortunately due to varied reports , no definite consensus and routine medical practice has been approved for it. The objective of the study is to observe the association of Ki-67 index using St. Gallen Conference criteria in invasive ductal carcinoma breast in Pakistani Population. Methods: Eighty-three patients with confirmed light microscopic diagnosis of primary invasive ductal carcinoma were recruited in this prospective study . Expression of Ki67 was determined by classifying as low (<15%) and high (>15%) Ki67 in tumour. Statistical analysis was performed to observe the association of Ki-67 with clinicopathological parameters and molecular group (i.e., Luminal A, Luminal B, Her2 enriched and triple negative). Results: Out of 83 patients, 73.5% of patients showed >15% Ki67 (p value <0.001). High expression of Ki 67 (>15%) was observed in 3.6%, 21.7% and 48.2 % of Nottingham grade I, II and III (p value=0.017) respectively.  Among molecular group, high expression of Ki67 was observed 20.5% in Luminal A, 9.6% in Luminal B, 15.7% in Her2 enriched and 27.7% in triple negative groups (p= 0.017). There was no significant association observed in expression of Ki 67 among lymph node stage, tumour stage and Nottingham prognostic index. Conclusion: Higher Ki-67 reactivity is usually associated with higher-grade morphology of tumour. It can act as an independent predictor in assessment of tumour behavior. However, larger validation clinical studies are still required for confirmation of its importance and for routine practice.     

Molecular Subtypes of Breast Cancers from Myanmar Women: A Study of 91 Cases at Two Pathology Centers

Background: Breast cancer is the most common cancer in Myanmar women. Revealing the hormonal receptor status, human epidermal growth factor receptor 2 (HER2) and Ki-67 expression is useful for estimating patient prognosis as well as determination of treatment strategy. However, immunohistochemical features and classification of molecular subtypes in breast cancers from Myanmar remain unknown. Methods: The clinicopathological features of 91 breast cancers from Myanmar women were examined. Immunohistochemistry was performed on tissue specimens with antibodies to estrogen receptor (ER), progesterone receptor (PgR), HER2, Ki-67, cytokeratin (CK)5/6 and CK14. Immunohistochemistry-based molecular subtyping was conducted. Results: Breast cancers in Myanmar women were relatively large, high grade with frequent metastatic lymph nodes. Of the 91 patients, tumors with ER positive, PgR positive, and HER2 positive were 57.1%, 37.4%, and 28.6%, respectively. The most prevalent subtype was luminal B (HER2-) (39.6%), followed by HER2 (22.0%), triple negative (TN)-basal-like (12.1%), luminal A (11.0%), TN-null (8.8%) and luminal B (HER2+) (6.6%). The mean Ki-67 expression of 91 cases was 33.9% (33.9% ± 19.2%) and the median was 28% (range; 4%-90%). The mean Ki-67 expression of luminal A, luminal B, HER2 and TN-basal-like/ null was 7%, 30%, 40%, and 57%/43%, respectively. A higher Ki-67 expression significantly correlated with a higher grade, larger size and higher stage of malignancy. Conclusions: We, for the first time, investigated the histopathological features of breast cancers from Myanmar women. Myanmar breast cancers appeared to be aggressive in nature, as evidenced by high frequency of poor-prognosis subtypes with high level of Ki-67 expression.     

Ki-67表达与多西他赛联合顺铂治疗三阴性乳腺癌疗效的关系

目的：探讨三阴性乳腺癌（ TNBC）组织Ki-67表达与多西他赛联合顺铂化疗疗效之间的关系。方法选取术后胸壁局部复发和（或）区域淋巴结转移的女性TNBC患者50例,复发或转移病灶行穿刺活检术,应用免疫组化方法检测Ki-67的表达,分为区域淋巴结转移组、无区域淋巴结转移组,Ki-67阳性表达组及阴性表达组。应用多西他赛联合顺铂方案化疗,3周期后进行疗效评价。结果区域淋巴结转移组及无区域淋巴结转移组Ki-67阳性表达差异有统计学意义（χ2=4.402,P=0.036）。3周期化疗后Ki-67阳性表达组有效率85.71%（30/35）,Ki-67阴性表达组有效率60.00%（9/15）,差异有统计学意义（χ2=4.406,P=0.044）。结论多西他赛联合顺铂治疗术后出现胸壁局部复发和（或）区域淋巴结转移的TNBC疗效较好, Ki-67阳性表达的TNBC患者对该方案化疗更敏感。     

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.     

Survival Rates of Invasive Breast Cancer among Ethnic Chinese Women Born in East Asia and the United States

Background: Few studies have compared the breast cancer survival rates of US born ethnic Chinese women and ‍the survival rates of Chinese immigrants. The main purpose of this study is to explore the difference of breast cancer ‍survival rates between the two populations and compare the survival rates to those of Caucasians born in the US. ‍Methods: Between 1973 and 2002, 365,215 women who had been diagnosed with primary invasive breast cancer ‍(ICD-O-2 C500:C509) were recorded in the Surveillance, Epidemiology, and End Results (SEER) registries. Of the ‍316,881 breast cancer patients who were white, 180,835 (57%) were born in the United States, 20,983 (7%) were ‍born elsewhere, and 115,063 (36%) had unknown birthplaces. Among the 3,634 breast cancer patients who were ‍ethnically Chinese, 952 (26%) patients were born in the US, 1,356 (37%) were born in East Asia, 146 (4%) were born ‍elsewhere, and 1,180 (33%) had unknown birthplaces. We compared the survival rates and estimated the risk ratios ‍(RRs) by the Kaplan-Meier estimates and the Cox proportional hazards models. Results: A lower 5-year overall ‍survival rate of breast cancer was observed among Chinese women born in East Asia (0.74, 95% CI=0.72-0.77) than ‍those born in the U.S. (0.79, 95% CI=0.76-0.81), with an adjusted hazards ratio of 1.22 (95% CI=1.06-1.40). The 5- ‍year survival rates for SEER stage were higher among Chinese women born in the U.S. (localized: 0.90, 95% CI=0.87- ‍0.93; regional: 0.71, 95% CI=66-0.77; distant: 0.16, 95% CI=0.06-0.25) than that among Chinese women born in ‍East Asia (localized: 0.86, 95% CI=0.83-0.89; regional: 0.68, 95% CI=0.63-0.73; distant: 0.16, 95% CI=0.07-0.25). ‍Higher 5-year survival rates among Chinese women born in the U.S. in comparison to Chinese women born in East ‍Asia were also observed in different calendar years (1973-1980, 1981-1990, 1991-2002), in surgery and radiation ‍therapy. Conclusions: Our analysis showed that among the Chinese breast cancer patients, women born in East Asia ‍had lower 5-year survival rates than women born in the United States. SEER stage, grade, and tumor size appear to ‍be important prognostic factors. The poor 5-year survival rates among Chinese women born in East Asia indicate ‍potential problems of accessing medical facilities for early detection, diagnosis and treatment because of potential ‍language and culture barriers, lower education level, as well as stress of the first generation of migrant Chinese ‍women in the United States.     

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.     

Associations Between Mammography and Ultrasound Imaging Features and Molecular Characteristics of Triple-negative Breast Cancer

Background: The triple-negative breast cancer (TNBC) is an aggressive cancer characterized by the absenceof estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2).Preoperative mammography and ultrasound features of TNBC may potentially suggest characteristics of thedisease and assist in treatment decisions. Materials and Methods: The study covered 153 patients with TNBCfrom May 2011 to May 2012 who were confirmed by postoperative pathology results in our hospital. We comparedthe radiological findings among the patients and sought to determine the significant iconographic features. Thebiomarkers p53 and Ki-67 are regarded as significant factors in TNBC. They were therefore used to divide theTNBC into four groups for assessment of relationships with TNBC imaging features. Results: On mammography,most TNBCs exhibit obscure (44.3%) masses. On ultrasound, the majority of masses (95.4%) were predominantlyindistinct (50.7%), irregular (76.0%) or featuring posterior echo enhancement/shadowing. Color Doppler flowimaging (CDFI) emphasized hypervascular (32.9%) masses. Differences in CDFI by ultrasound among the fourgroups were statistically significant (p=0.009). There were obvious differences in the percentages of spiculatedmargin (p=0.049) and intensive posterior echo (p=0.006) with spotty flow imaging by ultrasound between theKi-67 (+) p53 (+) and other groups. Conclusions: A combination of mammography and ultrasound revealedthe imaging characteristics of TNBC included an obscure mass with less attenuated posterior echoes and somevascularity. A worse prognosis was associated with spiculated margin and intensive posterior echoes with spottyflow imaging.     

Higher Ki67 Expression is Associates With Unfavorable Prognostic Factors and Shorter Survival in Breast Cancer

Background: The prognostic value of the Ki67 expression level is yet unclear in breast cancer. The aim of thisstudy was to investigate the association between Ki67 expression levels and prognostic factors such as grade, Her2and hormone receptor expression status in breast cancers. Materials and Methods: Clinical and pathologicalfeatures of the patients with breast cancer were retreived from the hospital records. Results: In this study, 163patients with breast cancer were analyzed, with a mean age of 53.4±12.2 years. Median Ki67 positivity was 20%and Ki67-high tumors were significantly associated with high grade (p<0.001), lymphovascular invasion (p=0.001),estrogen receptor (ER) negativity (p=0.035), Her2 positivity (p=0.001), advanced stage (p<0.001) and lymphnode positivity (p<0.003) . Lower Ki67 levels were significantly associated with longer median relapse-free andoverall survival compared to those of higher Ki67 levels. Conclusions: High Ki67 expression is associated withER negativity, Her2 positivity, higher grade and axillary lymph node involvement in breast cancers. The levelof Ki67 expression is a prognostic factor predicting relapse-free and overall survival in breast cancer patients.     

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。