Triple-negative high-risk breast cancer derives particular benefit from dose intensification of adjuvant chemotherapy: results of WSG AM-01 trial.

BACKGROUND: This paper evaluates the prognostic and predictive impact of protein expression of various molecular markers in high-risk breast cancer (HRBC) patients with >9 involved lymph nodes, who received different chemotherapy dose-intensification strategies within a prospective randomized WSG AM-01 trial. MATERIALS AND METHODS: Paraffin-embedded tumors from 236 patients, who were randomly assigned to dose-dense conventional chemotherapy with four cycles of E(90)C(600) followed by three cycles of C(600)M(40)F(600) every 2 weeks (DD) or a rapidly cycled tandem high-dose regimen with two cycles of E(90)C(600) every 2 weeks followed by two cycles of E(90)C(3000)Thiotepa(400) every 3 weeks (HD), were available for retrospective central pathological review (116 HD/120 DD). Expression of estrogen receptor (ER), progesterone receptor (PR), MIB-1, epidermal growth factor receptor, and Her-2/neu was evaluated immunohistochemically using tissue microarrays. Results were correlated with follow-up data and treatment effects by proportional hazard Cox regression models (including interaction analysis). RESULTS: After a median follow-up of 61.7 months, 5-year event-free survival (EFS) as well as overall survival (OS) rates for the 236 patients were significantly better in the HD arm: EFS: 62% versus 41% [hazard ratio (HR) = 0.60, 95% CI 0.43-0.85, P = 0.004]; OS: 76% versus 61% (HR = 0.58, 95% CI 0.39-0.87, P = 0.007). In multivariate analysis, HD, tumor size <3 cm, positive PR, negative MIB-1 staining, and grade 1/2 were associated with favorable outcome. Interaction analysis showed that regarding predictive effects, triple negative (ER/PR/Her-2/neu) and G3 tumors derived most benefit from HD. CONCLUSION: Tandem HD improves both EFS and OS in HRBC. This therapy effect may be partly attributable to superior efficacy in the subgroup of triple-negative tumors and/or G3 with their poor prognostic marker profile.     

热休克因子(HSF1)在乳腺癌中的表达及与预后的关系

目的：探讨热休克因子（heat shock factor 1，HSF。）在乳腺癌中的表达，及其在乳腺癌预后中所起的作用。方法：采用免疫组织化学方法检测62例手术切除的乳腺癌组织中HSF1的表达，探讨其与临床病理特征的关系及对预后的影响。结果：HSF1在乳腺癌组织中的阳性表达率为29．0％（18／62）。HSF1表达与月经状况存在相关（P=0．004），但与肿瘤大小、淋巴结转移个数以及组织学分级之间均不具相关性。HSF1阴性表达组无病生存期及总生存期均明显优于HSF1阳性表达组（P=0．0057及P=0．0251）。Cox回归单因素分析显示淋巴结转移个数、组织学分级、肿瘤大小、HSF1阳性表达及TNM分期与无病生存期及总生存期均明显相关；Cox回归多因素分析表明腋淋巴结转移个数、组织学分级、肿瘤大小与无病生存期及总生存期明显相关，而HSF1阳性表达及TNM分期最终未进入Cox回归模型。结论：HSF1在乳腺癌中有一定程度的表达，且HSF1表达与乳腺癌患者无病生存期及总生存期的缩短有关，有可能成为判断乳腺癌患者预后的指标。     

Hypoxia inducible factor-1alpha is a prognostic marker in premenopausal patients with intermediate to highly differentiated breast cancer but not a predictive marker for tamoxifen response

Hypoxia is common in many solid tumours, including breast cancer. Hypoxia triggers the expression of hypoxia inducible factor-1alpha (HIF-1alpha), and HIF-1alpha has been associated with an impaired prognosis in breast cancer and down-regulation of the oestrogen receptor (ER), potentially affecting the treatment efficiency of antioestrogens. The role of HIF-1alpha regarding prognostic and treatment predictive information in breast cancer has not been established and we therefore analyzed HIF-1alpha using immunohistochemistry in a cohort of 377 premenopausal stage II breast cancers arranged in a tissue microarray. The patients were included in a randomized trial with either 2 years of tamoxifen or no adjuvant treatment. The tamoxifen treatment effect could be studied in subgroups of breast cancer and pure prognostic information could be scrutinized for untreated control patients. HIF-1alpha was scored as positive in 24% of the tumours and correlated positively to tumour size, Nottingham histological grade (NHG), Ki-67, Her2 and cyclin E expression and negatively to lymph node status, cyclin D1, ER and PR (progesterone receptor) expression. Surprisingly, there was no difference in tamoxifen response for patients with high or low HIF-1alpha expressing tumours. In lymph node-positive patients as well as NHG 1/2 tumours, high HIF-1alpha protein expression was significantly associated with an impaired recurrence-free survival (p=0.014, 0.018). When analyzing the subgroup of NHG 1/2 tumours, a high HIF-1alpha expression was the only independent significant prognostic marker in multivariate analysis, including standard prognostic markers, suggesting that HIF-1alpha might be a useful prognostic marker in this subgroup of breast cancer, with a rather good but diverse prognosis.     

High Ep-CAM Expression is Associated with Poor Prognosis in Node-positive Breast Cancer

Previous studies in small series of patients with invasive breast cancer suggested a prognostic value of Ep-CAM overexpression in primary tumor tissue. To corroborate these findings, we performed a retrospective analysis of Ep-CAM expression using a tissue microarray containing tissue specimens from a large patient set. Ep-CAM expression was evaluated by immunohistochemistry in breast cancer tissue from 1715 patients with documented raw survival data. High level Ep-CAM expression (overexpression) was found in 41.7% of tumor samples, low level expression was found in 48.0% and no expression in 10.3% of tumor samples. Ep-CAM expression predicted poor overall survival in this patient cohort (p < 0.0001). Overall survival decreased significantly with increasing Ep-CAM expression. However, in this patient sample Ep-CAM expression was not an independent prognostic marker by multivariate analysis. Subgroup analysis revealed that Ep-CAM expression was a prognostic marker in node-positive (p < 0.0001) but not in node-negative (p = 0.58) breast cancer patients. Intriguingly, Ep-CAM expression was predictive for a dismal prognosis in patients receiving adjuvant cytotoxic (p = 0.03) or hormonal therapy (p < 0.0001) but not in untreated patients (p = 0.41). In summary, this study provides strong evidence that expression of Ep-CAM is a powerful marker of poor prognosis in node-positive invasive breast carcinoma and a potential predictive marker of sensitivity to adjuvant hormonal and/or cytotoxic treatment modalities.     

Hypoxia-inducible factor 1α is closely linked to an aggressive phenotype in breast cancer

PURPOSE: The aim of this study is to clarify characteristics of invasive breast cancer with expression of Hypoxia-induced factor 1alpha (HIF-1alpha) which is induced by hypoxia and signal transduction of growth factors. EXPERIMENTAL DESIGN : We examined, by immunohistochemical analysis, the expression of HIF-1alpha in normal breast tissue, benign disorders and breast cancer. In invasive breast cancer, we investigated the correlation between expression of HIF-1alpha and clinicopathological and biological factors. We also studied the prognostic value of HIF-1alpha in breast cancer. RESULTS : HIF-1alpha was mainly detected in tumor cell nuclei. In the 171 cases of invasive breast cancer examined, nuclear HIF-1alpha expression was detected in 63 (36.8%) cases. Immunoreactive nuclear HIF-1alpha was correlated with tumor size (p = 0.0013), lymph node metastasis (p = 0.0005), tumor stage (p = 0.0031) and histological grade (p = 0.0074). Elevated HIF-1alpha levels was also associated with hormone receptor negativity (p = 0.0025), HER2 overexpression (p = 0.0053), high Ki67 labeling index (p = 0.0002), increased levels of VEGF (p < 0.0001), COX-2 overexpression (p = 0.0029) and increased nuclear p53 (p = 0.0048). In terms of the possible use of HIF-1alpha as a prognostic indicator, patients who had increased HIF-1alpha levels in their tumor showed shorter disease-free survival (DFS) (p < 0.0001) and overall survival (OS) (p = 0.0002) than those lacking HIF-1alpha in univariate analysis. In multivariate analysis of DFS and OS, HIF-1alpha was identified an independent prognostic factor. CONCLUSIONS: These findings suggest that HIF-1alpha was closely linked to an aggressive phenotype in breast cancer. It may be useful to study the expression of HIF-1alpha using immunohistochemical analysis for better understanding of the tumor characteristics of breast cancer.     

Identifying good prognosis group of breast cancer patients with 1-3 positive axillary nodes for adjuvant cyclophosphamide, methotrexate and 5-fluorouracil (CMF) chemotherapy

OBJECTIVE: We conducted a retrospective analysis of prognosis factors for survival in breast cancer patients with 1-3 axillary lymph node metastases and tried to identify a subset of patients with good prognosis suitable for cyclophosphamide, methotrexate and 5-fluorouracil (CMF) adjuvant chemotherapy. METHODS: A cohort of 446 breast cancer patients received definite surgery and adjuvant chemotherapy with CMF at Chang Gung Memorial Hospital from 1990 to 1998. They were enrolled in the study. The median follow-up time was 69 months. Prognostic factors including age, tumor size, number of involved nodes, steroid receptor status, tumor ploidy, synthetic-phase fraction, histologic grade and administration of tamoxifen were analysed for disease-free survival (DFS) and overall survival (OS) by Cox regression model. RESULTS: The estimated 5 year OS and DFS for all patients were 85.4 and 71.5%, respectively. Multivariate analysis revealed that tumor size, age and estrogen receptor (ER) status were independent prognostic factors for OS, and tumor size, age, ER status and number of involved nodes were independent prognostic factors for DFS. The 5 year OS rates of the low-risk group (age >40, tumor < or =3 cm and positive ER) and average-risk group (either age < or =40, tumor >3 cm or negative ER) were 98.8 and 82.4%, respectively (P = 0.0001). The 5 year DFS of the low-risk and high-risk group were 88.2 and 67.7%, respectively (P = 0.0001). CONCLUSION: Among breast cancer patients with 1-3 positive lymph nodes excellent survival rate was found in those who had favorable prognostic factors, including age >40, tumor size < or =3 cm and positive ER. Adjuvant chemotherapy with CMF regimen is optimal for these low-risk patients.     

Ki-67与乳腺癌临床病理特征及新辅助化疗疗效的相关性

目的：分析Ki-67与乳腺癌临床病理特征对新辅助化疗（neoadjuvant chemotherapy,NCT）疗效和预后的影响,探讨NCT疗效的预测因素。方法用免疫组化法检测320例局部晚期乳腺癌患者癌组织中ER、PR、HER-2及Ki-67表达状况。进行NCT 4～6个周期后手术。分析临床病理特征与病理完全缓解率（patho-logic complete response,pCR）之间的关系。临床病理参数与疗效分析用χ2检验,影响预后因素用Cox多因素回归分析。结果 Ki-67表达与ER（r=－0.174,P=0.002）和PR（r=－0.132,P=0.019）呈负相关,与HER2（r=0.140, P=0.012）和乳腺肿瘤大小（r=0.132,P=0.019）呈正相关;ER阴性组pCR率显著高于ER阳性组（26.9%vs 7.4%,χ2=22.761,P=0.000）;PR阴性组pCR率显著高于阳性组（22.7%vs 10.9%,χ2=7.950,P=0.005）;Ki-67高表达组pCR率18.0%（41/228）优于Ki-67低表达组8.6%（8/92）（χ2=4.552,P=0.033）;化疗后Ki-67表达下降组pCR率19.8%（48/243）优于未下降组1.3%（1/77）（χ2=15.356,P=0.000）;各分子亚型间化疗疗效差异显著,Luminal A型pCR率为1.4%（1/71）,Luminal B型pCR率为15.3%（25/163）,HER2过表达型pCR率为31.3%（14/45）,三阴性型pCR率为22.0%（9/41）（χ2=20.639,P=0.000）;用Kaplan-Meier法进行生存分析,Ki-67低表达组无病生存时间（DFS）和总生存时间（OS）均优于Ki-67高表达组,两者均为P=0.034。结论 Ki-67高表达患者对化疗更敏感,但预后较差。化疗前Ki-67的表达和化疗后Ki-67变化是影响DFS独立的预后因素。ER、PR、Ki-67指数及分子分型可以作为NCT疗效的预测指标,Ki-67指数与ER、PR、HER2之间存在相关性。     

乳腺癌分子分型在新辅助化疗疗效和预后中的预测作用

[目的]探讨乳腺癌分子分型在新辅助化疗疗效及预后预测中的作用.[方法]对接受新辅助化疗方案治疗的157例乳腺癌患者进行回顾性分析.依据免疫组化雌激素受体(ER)、孕激素受体(PR)、人表皮生长因子受体2(Her2)表达水平将乳腺癌分为Luminal A、Luminal B、Her2阳性和三阴性4个分子分型,分析4个分子分型与临床病理因素、新辅助化疗疗效及3年生存率的相关性.[结果] 157例患者中,分子分型与肿瘤大小、淋巴结转移相关,T3～4期的三阴性型的比例高于T1～2期(P=0.003);N0、N1、N2、N3期的三阴性型的比例分别为44.4％、23.8％、25.6％和22.2％ (P=0.014).不同分子分型间新辅助化疗有效率无明显差异(P=0.632),而T分期(P=0.014)、N分期(P=0.031)与有效率明显相关.不同分子分型间新辅助化疗3年生存率有明显差异,Luminal A型最高,三阴性型最低(P=0.049).乳腺癌预后影响因素Cox回归模型分析提示分子分型(P=0.003)、年龄(P=0.007)、T分期(P=0.013)、N分期(P=0.000)是乳腺癌患者的独立预后因素.[结论]乳腺癌分子分型与肿瘤大小、淋巴结转移状态相关,能作为新辅助化疗远期疗效的独立预测因子.     

乳腺癌新辅助化疗10年预后的影响因素分析

目的:分析乳腺癌新辅助化疗患者的预后及影响因素。方法:回顾性分析302例乳腺癌新辅助化疗患者的临床资料,进行单因素和多因素分析影响预后的因素。结果:全组患者10年生存率为70.5%。多因素分析表明,新辅助化疗的近期疗效、是否三苯氧胺治疗、腋窝淋巴结临床及病理分期与患者的10年生存期有关。结论:新辅助化疗的近期疗效、是否三苯氧胺治疗、腋窝淋巴结临床及病理分期是影响乳腺癌新辅助化疗患者10年预后的独立因素。     

MACC1及其靶蛋白SPON2在乳腺癌中的表达及与预后的关系

目的:探讨结肠癌转移相关基因1（metastasis-associated in colon cancer 1,MACC1）及其靶蛋白SPON2在乳腺癌组织中的表达及与临床病理因素的相关性,并评估它们对乳腺癌患者预后的影响。方法:收集2011年1月至2011年12月间于同济医院行乳腺癌根治术的126例乳腺癌患者的癌和相应癌旁组织石蜡标本,应用免疫组化Envision法检测MACC1和SPON2蛋白在癌及癌旁组织中的表达,分析MACC1和SPON2表达与乳腺癌临床病理特征及患者预后的关系。结果:MACC1主要定位于细胞质及细胞膜,SPON2在细胞膜、细胞质及细胞外基质中出现表达,MACC1和SPON2蛋白在乳腺癌组织中的表达均明显高于癌旁组织（68.3% vs 21.4%和71.4% vs 17.5%,P均<0.01)。MACC1表达与乳腺癌患者组织学分级、TNM 分期、淋巴结转移、肿瘤复发显著相关（P均<0.05）;SPON2表达与患者TNM分期、淋巴结转移、Nottingham预后指数、肿瘤复发显著相关（P均＜0.05）;二者均与ER、PR及HER2状态无关（P>0.05）,且乳腺癌组织中MACC1和SPON2的表达呈显著正相关（P＜0.001）。Kaplan-Meier生存曲线显示,MACC1和SPON2高表达的患者总生存期（OS）和无进展生存期（PFS）均较短（P均<0.001）;Cox比例风险模型分析表明,MACC1和SPON2过表达是乳腺癌患者预后的独立影响因素（P均＜0.001）。结论:MACC1和SPON2可能参与了乳腺癌的发生、发展,在乳腺癌预后评估中具有一定价值,可能成为潜在的靶点为乳腺癌治疗提供一些新的思路。     

363例Luminal型乳腺癌的临床病理特点及预后分析

目的:探讨Luminal型不同分子亚型乳腺癌患者临床病理特点以及预后影响因素。方法:收集2006年1月至2013年2月诊治的363例Luminal型乳腺癌患者的临床和随访资料,分为Luminal A、Luminal B以及Luminal-HER2三组并分析临床病理参数与预后相关的因素。结果:363例Luminal型乳腺癌三种分子分型所占比例为51.5%、38.8%、9.7%,三组的发病年龄、肿瘤大小、组织学分级、淋巴结转移差异具有统计学意义（P<0.05）。局部复发率分别为2.7%、7.1%、20.0%;远处转移率为6.4%、12.1%、20.0%,Luminal-HER2型乳腺癌显著高于其余两组,且5年的无病生存以及总生存率明显低于其余两组,差异有统计学意义（P<0.05）。单因素分析和Cox多因素分析结果发现肿瘤大小、淋巴结转移、PR、HER2及内分泌治疗是Luminal型乳腺癌预后的独立影响因素(P<0.05)。结论:Luminal型乳腺癌中HER2过表达亚型患者侵袭性更强,预后更差。肿瘤较大、淋巴结转移、PR阴性、HER2过表达及未进行内分泌治疗是影响Luminal型乳腺癌预后的独立危险因素。     

Prognostic effect analysis of molecular subtype on young breast cancer patients

Objective

To make a prognostic effect analysis of molecular subtype on young breast cancer patients.

Methods

Totally 187 cases of young breast cancer patients less than 40 years old treated in Obstetrics and Gynecology Hospital of Fudan University between June 2005 and June 2011 were included in our study. We described their clinical-pathological characteristics, disease-free survival (DFS) rate, and overall survival (OS) rate after a median follow-up period of 61 months. The factors associated with prognosis were also evaluated by univariate and multivariate analyses.

Results

All patients were premenopausal, with an average age of 35.36±3.88 years old. The mean tumor size was 2.43±1.53 cm. Eighty-one cases had lymph node metastasis (43.3%), 126 cases had lymphovascular invasion (67.4%), and 125 cases had histological grade III (66.8%) disease. Twenty-seven cases (14.4%) were Luminal A subtype, 99 cases (52.9%) were Luminal B subtype, 29 cases (15.5%) were human epidermal growth factor receptor 2 (HER-2) overexpression subtype, while 32 cases (17.1%) were triple negative breast cancer (TNBC) subtype according to 2013 St Gallen expert consensus. One hundred and thirty-five cases underwent mastectomy whereas 52 cases had breast-conserving surgery. One hundred and seventy-eight cases underwent adjuvant or neoadjuvant chemotherapy. Recurrence or metastasis occurred in 29 cases, 13 of which died. The 5-year DFS and OS rates were 84% and 92%. Multivariate analysis showed that nodal status (P=0.041) and molecular subtype (P=0.037) were both independent prognostic factors of DFS, while nodal status (P=0.037) and TNBC subtype (P=0.048) were both independent prognostic factors of OS.

Conclusions

Molecular subtype is an independent prognostic factor of young breast cancer patients. TNBC has a high risk of relapse and death.     

Randomized trial of high-dose chemotherapy and hematopoietic progenitor-cell support in operable breast cancer with extensive lymph node involvement: final analysis with 7 years of follow-up.

BACKGROUND: The aim of this study was to present an update of overall (OS) and disease-free survival (DFS) and to evaluate the correlation between outcome and pathological findings at surgery in a randomized trial of high-dose chemotherapy following neoadjuvant chemotherapy and surgery in high-risk breast cancer patients. PATIENTS AND METHODS: Ninety-seven women <60 years of age with breast cancer and extensive axillary lymph node involvement received three courses of FE120C (5-fluorouracil 500 mg/m2, epirubicin 120 mg/m2, cyclophosphamide 500 mg/m2) followed by surgery. Eighty-one patients were randomized to receive either a fourth FE120C course alone or a fourth FE120C course followed by high-dose chemotherapy (cyclophosphamide 6 g/m2, thiotepa 480 mg/m2, carboplatin 1600 mg/m2). We performed a univariate analysis on possible prognostic factors and analyzed the sites of relapse. RESULTS: After a median follow-up of 6.9 years, 47 (48%) patients were alive, of whom 36 (38%) were without disease. Sixty patients relapsed after treatment. One patient died of myelodysplastic syndrome, without a relapse. In intention-to-treat analysis, the 5-year DFS rates were 47.5% in the conventional treatment arm and 49% in the high-dose arm, and the 5-year OS rates were 62.5% and 61%, respectively. In the univariate analysis, the clinical T-stage before chemotherapy and the number of tumor-positive axillary lymph nodes after induction chemotherapy (P = 0.027) were significant prognostic factors for OS. The same factors (both P = 0.06) plus the estrogen receptor (P = 0.08) were borderline significant factors for DFS. CONCLUSIONS: After a median follow-up of 6.9 years there was no difference in OS or DFS rates between the two treatment groups. The number of tumor-positive axillary lymph nodes after induction chemotherapy and the clinical T-stage before chemotherapy were significant factors for OS.     

Clinical significance of CD151 overexpression in subtypes of invasive breast cancer

Background:

CD151 is a member of the tetraspanin family, which interacts with laminin-binding integrins and other tetraspanins. This protein is implicated in motility, invasion, and metastasis of cancer cells, but the prevalence of CD151 expression in subtypes of breast cancers and its influence on clinical outcome remains to be evaluated.

Methods and results:

The immunohistochemistry-based tissue microarray analysis showed that 127 (14.3%) cases overexpressed CD151 among 886 breast cancer patients. CD151 overexpression was found to be significantly associated with larger tumour size, higher nodal stage, advanced stage, absence of oestrogen receptor and progesterone receptor, and human epidermal growth factor receptor 2 overexpression. CD151 overexpression resulted in poorer overall survival (OS) (P<0.001) and disease-free survival (P=0.02), and stage II and III patients with CD151 overexpression demonstrated substantially poorer OS (P=0.0474 and 0.0169). In the five subtypes analyses, CD151 overexpression retained its adverse impact on OS in the Luminal A (P=0.0105) and quintuple-negative breast cancer (QNBC) subtypes, one subgroup of triple-negative breast cancer (P=0.0170). Multivariate analysis that included stage, subtype, and adjuvant chemotherapy showed that CD151 overexpression was independently associated with poor OS in invasive breast cancer.

Conclusion:

CD151 overexpression may be a potential molecular therapeutic target for breast cancer, especially in QNBC subtype and more advanced stages of breast cancer.     

284例原发乳腺癌c-erbB2蛋白的表达及其与预后的关系

目的探讨c-erbB2癌蛋白在原发乳腺癌组织中的表达情况及其与预后的关系。方法采用免疫组化SP法检测284例原发乳腺癌组织的c-erbB2表达,并用统计学分析其与预后的关系。结果284例原发乳腺癌c-erbB2的阳性表达率为26．8％（76／284）,其表达与淋巴结转移数目（P=0．003）密切相关。单因素分析表明,c-erbB2是总生存时间（OS,P=0．002）和无病生存时间（DFS,P=0．024）的重要预后因素;多因素分析表明,c-erbB2是影响Os（P=0．023）的独立预后因素。此外,c-erbB2阳性的肿瘤患者较阴性者更易于发生内脏转移。而对于不同的淋巴结转移和ER状态,c-erbB2也有不同的预后价值。结论c-erbB2是影响原发乳腺癌患者OS的独立因素;在不同的淋巴结转移和ER状态下,其预后价值不同。     

Prognostic significance of Ep-CAM AND Her-2/neu overexpression in invasive breast cancer

To assess the frequency and prognostic impact of Ep-CAM and Her-2/neu overexpression in patients with breast cancer and to determine its relationship with other prognostic markers, 205 breast cancer patients with a median follow-up of 10.8 years were enrolled in this retrospective study. Overexpression of Ep-CAM and Her-2/neu in tumor tissue samples was assessed by immunohistochemistry. Tumors presenting a Her-2/neu 2+ staining were additionally analyzed by FISH to exclude false positive results. Ep-CAM and Her-2/neu overexpression was found in 35.6% and 19.5% of the tumor samples, respectively. Both Ep-CAM and Her-2/neu overexpression were predictive for poor disease-free (DFS) and disease-related overall survival (DROS). Concurrent Ep-CAM and Her-2/neu overexpression was present in 13.2% of tumor specimens and had an additive negative impact on DFS and DROS. This minority of patients had a median time to relapse of only 34 months, whereas the median time to relapse was not reached in the patient population without Her-2/neu and Ep-CAM overexpression. By multivariate analysis Ep-CAM overexpression proved to be an indicator of poor prognosis, independent of tumor size, histologic grade, hormone receptor expression and Her-2/neu overexpression. In conclusion, overexpression of Ep-CAM and Her-2/neu complement each other as predictors for poor prognosis in patients with invasive breast cancer. Determination of these tumor markers should help in assigning breast cancer patients to 1 of 3 distinct risk categories.     

Overexpression of matrix-metalloproteinase-9 in human breast cancer: a potential favourable indicator in node-negative patients

Matrix metalloprotease-9 (MMP-9; 92 kDa type IV collaganase, gelatinase B) is regarded as, important for degradation of the basement membrane and extracellular matrix during cancer invasion and other tissue-remodelling events. In this study we evaluate the prognostic value of MMP-9, by immunoperoxidase staining in a series of 210 breast cancer tissues. The results were quantitated using the HSCORE system, which consider both staining intensity and the percentage of cells stained at given intensities. MMP-9 status was compared with the concentration of cytosolic Cathepsin-D and with other established prognostic factors, in terms of disease free survival and overall survival. The median follow-up period was 62 months. MMP-9 staining was observed primarily in cancer cells, and to a lesser degree in surrounding stromal cells. MMP-9 expression was not detected in normal breast tissue. Levels of MMP-9 expression below the cut-off point were more frequently observed in larger (P = 0.014), invasive ductal histologic (P = 0.037), progesterone receptor (PR)-negative and PR-strong positive tumours (P< 0.001), as well as samples belonging to patients with stage III-IV disease (P = 0.009) and age 45-55 years (P = 0.011). In univariate analysis, node-negative breast cancer patients with tumors positive for MMP-9 had a considerable reduction in risk for relapse (RR = 0.45;P = 0.039) or death (RR = 0.32;P = 0.009). Multivariate analysis indicated that MMP-9 status was an independent favourable predictor of OS (RR = 0.47;P = 0.034) in node-negative but not in node-positive patients. Our results suggest that MMP-9 may be an independent favourable prognostic factor in node-negative breast cancer patients. The overexpression of MMP-9 in breast cancer may be also used as a marker to subdivide node negative breast cancer patients in order to determine the optimal treatment modality.     

乳腺癌分子分型在新辅助化疗疗效及预后预测中的作用

目的:探讨乳腺癌分子分型在新辅助化疗疗效及预后预测中的作用.方法:收集漯河市中心医院收治的236例接受新辅助化疗患者的临床病理资料,分为Luminal A、Luminal B、Her-2阳性和三阴乳腺癌4种分子分型,分析分子分型与临床病理因素、新辅助化疗疗效及 5 年生存率的相关性.结果:236例患者中,107例(45.3%)为Luminal A亚型,47例(19.9%)为Luminal B亚型,27例(11.4%)为Her-2阳性亚型,55例(23.3%)为三阴乳腺癌亚型.Her-2阳性(25.9%)及三阴乳腺癌亚型(30.9%)的病理完全缓解(pCR)率明显高于Luminal亚型(Luminal A亚型 4.7%及Luminal B亚型 8.5%),差异有统计学意义(P<0.05).与Luminal亚型相比,Her-2阳性及三阴乳腺癌亚型具有更差的5年无病生存和总生存(P<0.01);获得pCR的乳腺癌患者的5年无病生存和总生存明显高于化疗后仍有癌残留的患者(P<0.05).结论:相对于Luminal亚型,Her-2 阳性和三阴乳腺癌亚型对新辅助化疗更为敏感,更易达到pCR;但是Her-2阳性和三阴乳腺癌亚型预后反而更差.     

HER-2阳性乳腺癌患者新辅助化疗联合曲妥珠单抗治疗的影响因素及预后分析

目的:探讨人类表皮生长因子受体（human epidermal growth factor receptor 2,HER-2）阳性乳腺癌患者应用新辅助化疗联合曲妥珠单抗的疗效及其预后的影响因素。方法:选取2014年01月01日至2018年12月31日郑州市第三人民医院乳腺甲状腺外科收治经穿刺病理证实为乳腺癌的患者151例,免疫组化结果均显示为HER-2阳性,并行新辅助化疗,根据患者经济条件及意愿选择是否接受曲妥珠单抗治疗,将其分为单纯新辅助化疗组（neoadjuvant chemotherapy,NAC）94例,新辅助化疗联合曲妥珠单抗组（NAC+H）57例,对比两组患者无病生存期（disease-free survival,DFS）和总生存期（overall survival,OS）情况,并分析影响预后的相关因素。结果: 151例HER-2阳性乳腺癌患者中,NAC+H组患者DFS（P=0.046）和OS（P=0.026）均明显优于NAC组,两组比较差异具有统计学意义。术前淋巴结状态、术后淋巴结状态、肿瘤大小、MP分级是影响患者DFS和OS的主要影响因素（P值分别为0.032、0.018、0.038、0.010）。结论:接受新辅助化疗联合曲妥珠单抗的HER-2阳性乳腺癌患者预后较好,两组在新辅助治疗后肿瘤大小、淋巴结状态及MP分级结果存在明显差异,该结果对选择合理的治疗方案、判断预后有重要作用。     

Low Expression of Tyrosine-protein Phosphatase Nonreceptor Type 12 is Associated with Lymph Node Metastasis and Poor Prognosis in Operable Triple-negative Breast Cancer

Background: Low tyrosine-protein phosphatase nonreceptor type 12 (PTPN12) expression may be associatedwith breast cancer growth, proliferation, and metastasis. However, the prognostic value of PTPN12 in breastcancer has not been clearly identified. Patients and Methods: 51 triple-negative breast cancer (TNBC) patientsand 83 non-TNBC patients with a histopathology diagnosis from October 2001 to September 2006 were includedin this study. Immunohistochemical staining for PTPN12 on tissue microarrays was conducted. Results: HighPTPN12 expression was seen in 39.2% of TNBC and 60.2 % of non-TNBC cases. Low PTPN12 expressionwas associated with lymph node status (p = 0.002) and distant metastatic relapse (p = 0.002) in TNBC patients.Similarly, low PTPN12 expression in non-TNBC patients was significantly correlated with lymph node status(p = 0.002), stage (p = 0.002) and distant metastatic relapse (p = 0.039). The high PTPN12 expression group wasassociated with longer DFS and OS compared with low PTPN12 expression group only in TNBC cases (p =0.005, p = 0.015), according to univariate Cox regression analysis. Conclusion: These findings provide evidencethat low expression of PTPN12 is associated with worse prognosis and may be used as a potential prognosticbiomarker in TNBC patients.