Analysis of clinicopathological factors associated with bone metastasis in breast cancer

Breast cancer is the second leading cause of cancer death in women today. Once breast cancer metastasizes to bone, mortality increases. Thus, there is an urgent need to identify patients with high risk of bone metastasis, and to find predictive factors for the occurrence of bone metastasis at an earlier stage of breast cancer. Three hundred and sixty patients with pathologically proved breast cancer visiting the Department of Nuclear Medicine for whole body bone scan from January 2006 and January 2009 were investigated in this study. Clinicopathological information was obtained, which consisted of age, menopausal status, clinical staging, lymph node stage, histological grade, the expression of estrogen receptor (ER), progesterone receptor (PR) and epidermal growth factor receptor 2 (HER2). Correlation between bone metastasis and the associated factors was tested by using the Chi-square test. A Cox multivariate analysis was used to assess the factors which independently contributed to survival after bone metastasis in breast cancer patients. Survival curves were drawn for metastasis-free interval and the independent factors which contributed to survival, using the Kaplan-Meier method. Twenty-four patients were excluded from subsequent analysis. Three hundred and thirty-six enrolled patients ranged in age from 22 to 77 years (mean, 47.8 years). ER/PR status [ER(+) vs. ER(-), χ2 =4.328, P=0.037; ER(+)PR(+) vs. ER(+)PR(-), χ2 =4.425, P=0.035] and histological grade (χ2 =7.131, P=0.028) were significantly associated with bone metastasis. ER status (χ2 =8.315, P=0.004) and metastasis-free interval (χ2=6.863, P=0.009) were independent prognostic factors for survival in breast cancer patients with bone metastasis. Our study suggested that ER/PR status and histological grade are risk factors for the development of bone metastasis in breast cancer patients. However, ER status and metastasis-free inter- val are independent prognostic factors for survival in breast cancer patients with bone metastasis. Breast cancer bone metastasis has its unique characteristics, which is helpful to choose the appropriate treat- ment for breast cancer patients with bone metastasis.     

Comparison of immunohistochemistry with fluorescence in situ hybridization in determining the human epidermal growth factor receptor 2 status of breast cancer specimens: a multicenter study of 3 149 Chinese patients

Background Accurate detection of human epidermal growth factor receptor 2 （HER2） expression and gene amplification is crucial for the application of HER2-specific therapy and for evaluating the response of patients with breast cancer.A uniform and standard procedure of immunohistochemistry （IHC） and fluorescence in situ hybridization （FISH） needs to be established for evaluating the HER2 status in breast cancer tissues for the treatment of patients with real HER2-positive tumors.The present multicenter study was aimed to examine the HER2 status in breast cancer specimens from Chinese patients using both IHC and FISH methods.Methods A multicenter study was performed on the HER2 status in 3 149 breast cancer specimens from different ethnic populations and areas in China by IHC and FISH assays.The potential association of HER2 status with demographic and clinical characteristics was analyzed.Results The positive rates for HER2 over-expression and HER2 amplification were 23.3％ and 27.5％ in this study,respectively.The concordance between IHC and FISH was 71.2％ （K=0.494,P ＜0.001）.Furthermore,72.9％ of specimens with IHC 2＋ were negative to FISH.The discordance rates among laboratories were from 5％ to 28％ for IHC and 1％ to 16％ for FISH.HER2 amplification was associated significantly with advanced tumor stage （Ⅲ or Ⅳ,P=0.002）,large tumor size （＞5 cm,P=0.002）,moderate and poor histological grades （P ＜0.0001）,post-menopause （P ＜0.0001）,ER-PR-（P=0.002）,and having ＞4 lymph nodes affected （P ＜0.0001） in this population.The positive rates of HER2 amplification in specimens from Man and Hui Chinese were significantly higher than that in other Chinese populations.There are slightly higher positive rates of HER2 expression and amplification in Chinese patients with breast cancer.Conclusion These findings may provide new insights into understanding the epidemiological features of HER2 expression and amplification,and may be valuable for clinical practice.     

Treatment outcomes of occult breast carcinoma and prognostic analyses

Background The surgical management of occult breast cancer is controversial.We compared the outcomes of different treatments of occult breast cancer and evaluated the potential prognostic factors for overall survival and recurrence.Methods We retrospectively reviewed 77 patients who presented to our hospital from 1968 to 2011 with a diagnosis of occult breast cancer.Patients were divided into three groups：42 patients （63％） were treated with modified radical mastectomy＋axillary lymph node dissection （ALND）,16 patients （24％） were treated with ALND＋postoperative radiotherapy,and 9 patients （13％） with only ALND.Survival analyses were undertaken to compare the efficacy of these three treatments.Results Of the 77 patients with occult breast cancer,2 patients were lost to follow-up and 8 patients refused surgical treatment：67 patients （90.4％） were included in this analysis.The median follow-up was 62.2 （0.6-328.0）months.Kaplan-Meier analyses showed no significant difference in overall survival and recurrence-free survival between the three groups （P=0.494 and 0.397,respectively）.The prevalence of local recurrence was 11.9％ for the mastectomy＋ALND,18.8％ for ALND＋radiotherapy,and 11.1％ for ALND-only groups,and those for distant recurrence were 2.4％,12.5％,and 11.1％,respectively.Compared with progesterone receptor-negative subjects,progesterone receptor-positive patients had better overall survival and lower recurrence rates （P=0.057 and 0.062,respectively）.Conclusions There was no significant difference in outcomes between mastectomy and breast-preserving surgery.Expression of the progesterone receptor should be taken into account when evaluating the prognosis of occult breast cancer.     

Effects of diabetes mellitus on prognosis of the patients with colorectal cancer undergoing resection: a cohort study with 945 patients

Background Diabetes mellitus plays an important role in cancer prevalence and outcomes. The aim of this study was to evaluate the influence of DM on stages and outcomes among patients with colorectal cancer.Methods The study enrolled 945 patients who were diagnosed as having colorectal carcinoma from August 1994 to December 2002. In the cohort, 26 patients were diagnosed as having DM. With a median follow-up of 45.8 months,differences in overall survival and disease-free survival between the diabetes and non-diabetes groups were analyzed.Results Kaplan and Meier analysis showed that there were no significant differences between the two groups in overall survival rates at 3 years or 5 years. At 5 years, patients with DM, compared with patients without diabetes, experienced a significantly lower disease-free survival rate （34.2% diabetics vs. 55.1% non-diabetics; P=0.025）.Conclusions DM was associated with an increased risk of recurrence in patients with colorectal cancer.     

EFFECT OF POSTOPERATIVE RADIOTHERAPY ON THE RESULTS OF RADICAL MASTECTOMY FOR STAGE II BREAST CANCER

From April 1964 to December 1978, 1,684 pa- tients with primary breast cancer were admitted to our hospital. 260 0f them had unilateral breast cancer of Stage n according to p-TNM classifica tion of UICC. The size of the primary tumors was equal to or less than 5 cm in diameter. The axillary lymph nodes were involved pathologically in all patients. The 260 patients had a radical mastectomy with or without adjuvant radiotherapy. Their results were reviewed retrospectively. The survival rates, incidence of local recurrence and distant metastases were compared between the patients with and those without postoperative radiotherapy. The 3-, 5-, and 10-year survival rates were 67.9To, 52.8% and 40.5T。 in the group with radiotherapy, and 61.0'/o, 49.6t7。 and 28.9To in the group without radiotherapy respec tively (p>0.05). The incidence of local recurrence and regional metastases was 22.6To in the first group and 32.1To in the second group; the recurrence rate of the ipsilateral supraclavicular lymph nodes was 1.4Vo and 15.2To respectively (p<0.005). The rates of distant metastasis of the groups were nearly the same. The results suggest that radiotherapy after opera. tion may reduce the rate of local recurrence, par ticularly that of ipsilateral supraclavicular lymph nodes, and increase the 10-year survival rate of radical mastectomy.     

中医与西医治疗晚期非小细胞肺癌病人远期生存率的临床研究

Objective： To investigate the prognostic influence on long-term overall survival （OS） from treatment with Chinese medicine （CM） and chemotherapy or targeted therapy in advanced non-small-cell lung cancer （NSCLC） patients. Methods： The clinical data of 206 advanced NSCLC patients who were treated with CM and Western medicine in Beijing Cancer Hospital from April 1999 to July 2013 were retrospectively analyzed. Long-term survivors were defined as OS ≥ 3 years after treatment with CM and chemotherapy. Twenty-eight patients had OS ≥ 3 years, 178 had OS 〈 3 years, and all clinical data were statistically analyzed with the Cox model. Variables were gender, age, smoking status, performance status （PS） score, pathological type, clinical stage, first-line chemotherapy, targeted therapy, and use of CM. Univariate survival analysis was performed using the Kaplan-Meier method and log-rank sequential inspection. Multivariate survival analysis was used to analyze the meaningful factors of univariate survival analysis with the Cox model. Results： The survival rate of patients with OS ≥ 3 years was 13.6% （28/206）. Cox multivariate regression analysis showed that PS score, clinical stage, disease control rate to first-line chemotherapy, and use of CM were independent factors of long- term OS （all P〈0.05）. However, gender, age, smoking, and use of epidermal growth factor receptor tyrosine- kinase inhibitor were not significant （P〉0.05）. Conclusion： PS score, clinical stage, disease control rate to first- line chemotherapy, and use of CM are probably independent prognostic factors for long-term OS in patients with advanced NSCLC.     

Cyclin E Expression and Chemotherapeutic Sensitivity in Breast Cancer Cells

The effects of the cyclin E expression levels on chemotherapeutic sensitivity of breast cancer cell line were explored. After the cyclin E expression was knockdown in MDA-MB-435 by RNA interference, FACS analysis and SA-p-gal staining were used to evaluate the response sensitivity of breast cancer cells to DNA damage drugs (adriamycin, etc.). Adriamycin could induce G1 arrest in cyclin E knockdown MDA-MB-435 breast cell line and increase the percentage of cell senescence in cyclin E knockdown MDA-MB-435 cells. It was suggested that cyclin E knockdown could increase the chemotherapeutic sensitivity of breast cancer cells to DNA damage drugs.     

MMR, MCM2, Cyclin A, and TGFRB as prognostic factors for colorectal cancer: results of a 10-year prospective study using tissue microarray analysis

Background: The expression of genes encoding a number of pathogenetic pathways involved in colorectal cancer could potentially act as prognostic markers. Large prospective studies are required to establish their relevance to disease prognosis. Methods: We investigated the relevance of 19 markers in 790 patients enrolled in a large randomised trial of 5-fluorouracil using immunohistochemistry and chromogenic in situ hybridisation. The relationship between overall 10-year survival and marker status was assessed. Results: MCM2 and Cyclin A were significantly associated with overall survival. Elevated MCM2 expression was associated with a better prognosis (HR = 0.63, 95% CI: 0.46–0.86). Cyclin A expression above the median predicted an improved patient prognosis (HR = 0.71, 95% CI 0.53–0.95). For mismatch repair deficiency and TGFBRII overexpression there was a borderline association with a poorer prognosis (HR = 0.69, 95% CI: 0.46–1.04 and HR = 2.11, 95% CI: 1.02–4.40, respectively).No apparent associations were found for other markers （eg, VEGF, MMP2, TIMP2,Upa, SMAD4, PRL3, EGFR, AND HER2）. Conclusions: This study identified cell proliferation and cyclin A expression as prognostic indicators of patient outcome in colorectal cancer.     

XIAP as a prognostic marker of early recurrence of nonmuscular invasive bladder cancer

Background Dysregulation of apoptosis has been implicated not only in carcinogenesis and tumor progression but also in tumor recurrence. We investigated whether the expression of X-linked inhibitor of apoptosis （XIAP） might predict early recurrence in patients with non-muscular invasive bladder cancer. Methods The cohort comprised 176 consecutive patients with primary superficial bladder cancer treated with transurethral resection. Immunohistochemical staining using the standard avidin-bioUn-peroxidase technique and RT-PCR were used to detect XIAP protein and mRNA expressions in cancer tissues. The relationship between XIAP expression and clinicopathological characteristics, cancer recurrence were analyzed. Results XIAP expression was observed in 108 cases （61.4%） and no expression in 68. There was no correlation between XIAP expression rate and the tumor pathological grade, but was an apparent trend toward the increased XIAP levels from well （G1） to poor （G3） differentiated cancer. Eighty-two （46.6%） patients experienced tumor recurrence at a mean of 28.6 months of the follow-up; 66 of them expressed XIAP （61.1%） and 16 were XIAP negative （23.5%）. Twelve patients presented with invasive disease at the time of relapse and all of them expressed XIAP. Patients without XIAP expression or with low tumor grades had significantly higher recurrence-free survival than those with XIAP expression （log rank test ,P=-0.0015） or high tumor grades （log rank test P〈0.001）. Multivariate analysis revealed that XIAP expression, tumor grade, and tumor number were independent predictors for the recurrence of non-muscular invasive bladder cancer （P=-0.004, 0.016, and 0.043, respectively）. Conclusions XIAP may be considered as a new independent prognostic marker for early recurrence of non-muscular invasive bladder cancer.     

Prognostic significance of MDR-1 P-glycoprotein expression in breast cancer

Objective: To investigate the expression of MDR-1 P-glycoprotein(MDR-1 Pgp) in breast cancer and analyze its correlation to the biological behavior and prognosis of the disease. Methods:The expression of MDR-1 Pgp was examined in 75 cases of breast cancer patients by using three different monoclonal antibodies(JSB1, C219 and C494) with S-P immunohistochemisty. These patients were followed up for 5 years, and the correlation between MDR-1 Pgp expression, survival rate and lymph metastasis was analyzed. Results: Positive detection of MDR-1 Pgp by JSB1, C219 and C494 in 75 cases of breast cancer was 86.7%, 48% and 85.3%, respectively. MDR-1 Pgp expression was not related to ages of patients (P > 0.05). JSB1-detected expression of MDR-1 Pgp was related to lymph node metastasis(P < 0.05); while C219 and C494 were not(P > 0.05). The patients with MDR-1 Pgp expression positively detected by either two of the three antibodies, had five-year survival rate that was significantly higher than those positively detected by all the three antibodies(P < 0.05). Conclusion:Three antibodies should be used simultaneously to detect MDR-1 Pgp expression in breast cancer. Positive MDR-1 Pgp expression in breast cancer detected by all the three antibodies may represent a poor prognosis; while positive MDR-1 Pgp detection by JSB1 and C494 is associated with lymph metastasis.     

Geldanamycin对HER2/neu高表达人乳腺癌细胞系SKBr3增殖及迁移能力的影响

目的 探讨Hsp90抑制剂苯醌安莎霉素类抗生素(GA)对HER2/neu高表达人乳腺癌细胞系SKBr3增殖及迁移能力的影响.方法 用Western蛋白印迹法检测GA介导的HER2/neu酪氨酸激酶的降解;MTT法分析GA对肿瘤细胞存活率的影响;流式细胞仪测定GA对肿瘤细胞周期的影响;RT-PCR和real-time PCR分析GA对cyclin D1表达的影响以及分析GA对肿瘤细胞迁移能力的干预作用.结果 GA以剂量/时间依赖性的方式降解了HER2/neu酪氨酸激酶的表达并抑制了SKBr3乳腺癌细胞的增殖,这种增殖抑制效应表现在:GA干预后乳腺癌细胞的存活率明显降低;GA阻断了乳腺癌细胞细胞周期的进展,使细胞周期停滞于G1期,而这两种表现与cyclin D1表达量的减低有着明显的关系.GA的干预也同时降低了肿瘤细胞的迁移能力.结论本研究证实GA能够降解HER2/neu酪氨酸激酶并抑制HER2/neu高表达人乳腺癌细胞系SKBr3的增殖和迁移能力.     

人类表皮生长因子受体3在人表皮生长因子受体2阳性乳腺癌中的表达及其与预后的关系

目的：探讨人表皮生长因子受体3（human epidermal growth factor receptor-3,HER3）在人表皮生长因子受体2（human epidermal growth factor receptor-2,HER2）阳性乳腺癌中的表达及其与曲妥珠单抗治疗疗效、预后的关系。方法回顾性分析江苏省肿瘤医院2007年1月至2012年6月235例可手术HER2阳性乳腺癌的临床病理资料,免疫组化染色检测手术标本中HER3的表达情况,分析HER3在不同分子亚型HER2阳性乳腺癌中的表达及其与临床病理特征的关系,同时对所有患者进行随访,观察不同HER3表达组的无复发生存时间及其对曲妥珠单抗治疗疗效的影响。结果 HER3在Luminal B （ HER2＋）型乳腺癌中的阳性表达率为74.1％（100/135）,在HER2过表达型乳腺癌中的表达率为85.0％（85/100）,2者差异具有统计学意义（P＜0.05）。 Luminal B（HER2＋）型乳腺癌中组织学分级、淋巴结转移在不同HER3表达组中差异具有统计学意义（ P＜0.05）。 HER2过表达型乳腺癌中,肿块大小、组织学分级、淋巴结转移在不同HER3表达组中差异具有统计学意义（ P＜0.05）。不同分子亚型的HER2阳性乳腺癌中HER3阴性表达组的5年无复发生存率均高于HER3阳性表达组。在Luminal B（HER2＋）型乳腺癌并接受曲妥珠单抗治疗的患者中,不同HER3表达组的无复发生存时间差异无统计学意义[（26.1±177;0.5）个月vs （21.3±177;0.7）个月,P＝0.080],但在HER2过表达型乳腺癌患者中不同HER3表达组的无复发生存时间差异具有统计学意义[（26.4±177;0.4）个月vs （23.4±177;0.8）个月,P＝0.036]。结论 HER3与HER2阳性表达乳腺癌的预后不良相关,针对HER3的靶向治疗有望改善HER2和HER3阳性乳腺癌的预后。在HER2过表达型且HER3阴性乳腺癌患者中曲妥珠单抗治疗更能获益。     

乳腺癌中细胞周期素D1基因扩增和过表达及其与c-erbB-2的关系

目的：探讨细胞周期素D1基因和表达的改变在乳腺癌中的作用及其与c-erbB-2表达的关系。方法 采用原位分子杂交和免疫组织化学技术检测59例乳腺癌组织细胞周期素D1基因扩增、mRNA及其蛋白和c-erbB-2的表达。结果 27例（45．8％）细胞周期素D1蛋白过表达,其过表达与腋淋巴结转移相关（P＜0．05）。细胞周期素D1 DNA扩增、mRNA高表达和蛋白过表达三者基本一致,与c-erbB-2过表达无相关。结论 细胞周期素D1蛋白过表达在乳腺癌频发,其基因扩增和转不增加是其重要机制之一。细胞周期素D1和c-erbB-2在乳腺癌中各自发挥独立作用,两者同时检测更有助于判断预后。     

乳腺癌HER2基因荧光原位杂交与显色原位杂交检测对比研究

目的 对比研究荧光原位杂交(fluorescence in situ hybridization,FISH)和显色原位杂交(chromogenic in situ hybridization,CISH)在检测乳腺癌HER2基因扩增状态中的敏感性和准确性.方法 对32例经CISH法检测HER2基因状态的乳腺癌标本行回顾性...     

乳腺癌HER2、孕激素受体表达与生存期相关性的研究

目的研究乳腺癌HER2、孕激素受体(PR)与生存期的关系,探讨其成为乳腺癌预后指标的可行性。方法采用免疫组化检测185例乳腺癌标本HER2和PR的表达,并随访其生存时间。结果(1)有10年内预后随访资料者120例,占总人数的64.9%,其中死亡28例,占15%;(2)HER2、PR的阳性表达率分别为57.8%和62.7%;(3)HER2和PR各级生存率表达曲线比较,统计学有显著性意义(P<0.01),其中HER2与生存率呈负相关,PR与生存率呈正相关;(4)单变量分析表明:HER2是一个危险因素,影响生存时间缩短(P<0.01);PR是一个保护因素,其高表达预示生存期长(P<0.01)。(5)HER2联合PR多变量分析,只有PR有显著性意义(P=0.012)。结论HER2和PR均是乳腺癌独立的预后指标,HER2高表达提示预后不良,而PR高表达则预示患者有较高的生存率和较长的生存期。     

NUAK2蛋白在Luminal型乳腺癌组织中的表达及意义

目的评估NUAK2蛋白在Luminal型乳腺癌组织中的表达水平和临床意义。方法使用免疫组织化学方法,检测Luminal型乳腺癌患者组织标本中NUAK2蛋白的表达水平,与癌旁组织进行比较,并分析其与患者的临床特征、病理特征及预后的关系。结果NUAK2蛋白在Luminal型乳腺癌组织中的表达水平高于癌旁乳腺组织（P=0.032）;术后因肿瘤复发而死亡的患者,其肿瘤组织中的NUAK2蛋白表达水平也较高（P=0.037）;NUAK2蛋白高表达组患者更容易出现淋巴结转移（P=0.038）,且无复发生存率（P=0.035）和总体生存率（P=0.024）也明显下降;NUAK2蛋白表达水平升高与患者乳腺癌复发明显相关（P=0.011）。结论NUAK2蛋白在Luminal型乳腺癌组织中高表达,其表达水平与淋巴结的转移、肿瘤的复发和患者的预后存在相关性,推测NUAK2可能是乳腺癌的一个癌基因。     

赫赛汀联合辅助化疗对人类表皮生长因子受体2阳性早期乳腺癌患者预后影响的Meta分析

目的:应用meta分析的方法探讨赫赛汀(曲妥珠单抗)联合辅助化疗对人类表皮生长因子受体2(HER2)阳性早期乳腺癌患者预后的影响.方法:在MEDLINE,EMBase,Cochrane图书馆,临床试验注册库,google学术网,中国医院数字化图书馆,维普、万方数据库,历年美国临床肿瘤学会会议资料及欧洲灰色情报系统(SIGLE)中检索有关HER2阳性早期乳腺癌患者赫赛汀联合辅助化疗的前瞻性随机对照临床试验,按Meta分析软件(RevMan4.2)要求处理有关数据. 结果:从1996～2006年共有4项研究入选,合并后试验组共有4555例,对照组共有4561例.分析结果显示赫赛汀联合辅助化疗与单纯辅助化疗相比,无病生存率RR＝1.08(95% CI,1.06～1.09),P＜0.001;总体生存率RR=1.01(95% CI,1.01～1.02),P＝0.0003;远处复发率RR＝0.49(95% CI,0.42～0.57),P＜0.001;心脏事件发生率RR=3.93(95% CI,1.03～15.06),差异均有统计学意义(P＝0.05).结论:赫赛汀联合辅助化疗治疗HER2阳性早期乳腺癌能够显著提高患者的无病生存率、总体生存率,降低远期复发率,但可能有心脏毒性作用,心脏毒性在联用蒽环类药物(阿霉素)后尤为明显.     

三阴性乳腺癌的临床病理特点及预后因素分析

目的探讨三阴性（TN）乳腺癌的临床病理特点及影响预后的因素。方法回顾性分析515例乳腺癌患者,根据雌激素受体（ER）、孕激素受体（PR）和人表皮生长因子受体2（HER2）的表达,将其分为3组：三阴组（ER阴性、PR阴性、HER2阴性）、HR组（ER阳性或PR阳性、HER2阴性或阳性）、HER2组（ER阴性、PR阴性、HER2阳性）。分析各组的临床病理特点、复发及生存情况。结果三阴组与HR组、HER2组相比．患者年龄小、肿瘤较大、浸润性导管癌多见,淋巴结转移率与肿瘤大小有统计学意义;三阴组复发时间较早（2．32年）,复发率（23．91％）和死亡率（22．72％）均较高;患者复发风险呈先升后降的趋势：术后1～4年达到顶峰,之后下降。结论三阴性乳腺癌患者诊断时年龄小、原发肿瘤大、淋巴结转移率高、术后5年内复发和死亡风险高。     

提高乳癌HER2阳性检出率的免疫组化染色方法探讨

目的探讨提高乳癌人表皮生长因子受体2(HER2)阳性检出率的免疫组织化学染色方法。方法采用3种不同的方法对1 128例经病理确诊为乳癌的病人进行HER2检测。结果 3种抗原修复方法 HER2阳性结果比较差异均有显著性(Hc=7.34,q=15.59～66.55,P<0.01)。结论 TE高压修复法乳癌HER2阳性检出率优于EDTA煮沸法,EDTA煮沸法乳癌HER2阳性检出率优于枸橼酸微波修复法。