Human recombinant anti-HER2 monoclonal antibody--a new targeted treatment in breast cancer]

The HER2 protein is encoded by the HER2/neu gene and it is homologous to the epidermal growth factor receptor. Overexpression of HER2, usually in association with gene amplification, occurs in approximately 25-30% of breast cancers. There are currently several different methods available to evaluate HER2 status, e.g. immunohistochemical (IHC), and fluorescence in situ hybridization (FISH) assays. The HER2 protein is a viable therapeutic target. The humanized anti-HER2 monoclonal antibody trastuzumab (Herceptin) has demonstrated activity in clinical trials in women with metastatic breast cancer overexpressing HER2. The mechanisms of the action of this antibody involve disruption of DNA repair and induction of antibody-dependent cellular cytotoxicity. Response rates to the antibody given as a single agents in the treatment of HER2 overexpressing metastatic breast cancer have ranged from 12 to 27%. Patients who received trastuzumab in combination with chemotherapy had a significantly longer time to progression, higher overall survival compared with patients who had received chemotherapy alone. In the treatment of women with HER2 overexpressing tumors an overall response rate of 57% for combination trastuzumab plus paclitaxel compared with 25% for paclitaxel alone was found. Trastuzumab has an important role in the treatment of HER2 overexpressing metastatic breast cancer. Its place in adjuvant treatment has not been proved up to now. The optimal use of trastuzumab in the treatment of HER2 positive advanced breast cancer is under active investigation. Due to the high rate of clinical activity and low incidence of severe toxicity trastuzumab is a very promising drug in the treatment of breast cancer. The author's purpose was to summarize the results of the trials using trastuzumab treatment, and discuss the methods used to determine the HER2 status.     

辽宁省2003-2015年7255例艾滋病抗病毒治疗患者的生存分析

目的 探讨艾滋病（acquired immunodeficiency syndrome,AIDS）患者高效抗逆转录病毒治疗（highly active antiretroviral therapy,HAART）后的生存率及其影响因素。方法 采用回顾性队列研究方法,收集辽宁省2003-2015年7 255例接受HAART的人类免疫缺陷病毒（human immunodeficiency virus,HIV）感染者和AIDS患者的相关信息,用寿命表法分析其生存率,用Cox回归模型分析生存时间的影响因素。结果 共收集7 255例HIV/AIDS为研究对象,HAART后1、3、5年的累积生存率分别为97%、95%、93%,6～12年的累积生存率均为92%;其中HAART后艾滋病相关死亡269例,总病死率为1.99/100人年;Cox回归模型多因素分析显示,年龄30～59岁（HR=0.330,95%CI:0.203～0.538）、>59岁组（HR=0.569,95%CI:0.395～0.820）与<30岁组相比死亡风险低;文化程度初中（HR=0.503,95%CI:0.324～0.780）、高中及中专（HR=0.284,95%CI:0.200～0.405）、大专及以上组（HR=0.254,95%CI:0.169～0.381）与小学及以下组相比死亡风险低,感染途径为异性传播组与同性传播组相比死亡风险低（HR=0.540,95%CI:0.383～0.763）;基线CD4+T淋巴细胞计数≥200个/μl组与<50个/μl组相比死亡风险低（HR=0.316,95%CI:0.201～0.499）;BMI≥24.0 kg/m2组与<18.5 kg/m2组相比死亡风险低（HR=0.459,95%CI:0.344～0.611）。结论 辽宁省艾滋病抗病毒治疗效果稳定,5年生存率水平较高。疾病早期进行规范治疗是降低患者死亡风险、提高生存率的有效措施。     

盐城市2005-2015年艾滋病抗病毒治疗患者生存分析

目的 探索盐城市2005-2015年首次接受抗病毒治疗的艾滋病病毒感染者(HIV)/艾滋病病人(AIDS)的生存时间及影响因素。 方法 利用中国疾病预防控制系统艾滋病综合防治信息系统收集盐城市2005-2015年HIV/AIDS的生存、死亡信息,采用寿命表法分析患者的生存率,采用Cox比例风险模型分析可能影响生存时间的因素。 结果 共有670例接受抗病毒治疗的病例纳入本次研究,截止到研究结束时,有48例病人死于艾滋病相关疾病,占7.16%。抗病毒治疗后患者1~5年的累积生存率分别为0.93、0.91、0.91、0.88和0.88。多因素Cox比例风险模型分析结果显示,首次确诊HIV阳性时年龄25~<50岁组的死亡风险低于年龄≥50岁组(HR=0.350,95%CI:0.196~0.625,P<0.001),相对于基线CD4^＋T淋巴细胞计数＜50个/mm³组,CD4^＋T淋巴细胞计数50~<200个/mm³组、≥200个/mm³组的病例死亡风险均降低(HR=0.447,95%CI:0.216~0.925,P=0.030;HR=0.286,95%CI:0.148~0.552,P<0.001)。 结论 首次确诊HIV阳性时的年龄和基线CD4^＋T淋巴细胞计数影响HIV/AIDS的生存时间,提示扩大HIV监测检测覆盖面,早诊早治是提高患者生存率的关键。     

Evaluation of different plasmid DNA delivery systems for immunization against HER2/neu in a transgenic murine model of mammary carcinoma

Studies of DNA vaccination against HER2/neu showed the effectiveness of immunization protocols in models of transplantable or spontaneous tumors; scarce information, however, has been provided to identify the procedure of DNA administration that more effectively contributes to the activation of immune system against spontaneously arising HER2/neu-positive tumors. We compared the effectiveness of different procedures of DNA vaccine delivery (intradermic injection (ID), gene gun (GG) delivery and intramuscular injection (IM) alone or with electroporation) in a murine transgenic model of mammary carcinoma overexpressing HER2/neu. We highlighted the role of DNA delivery system in the success of DNA vaccination showing that, among the analysed methods, intramuscular injection of the vaccine, particularly when associated to electroporation, elicits a better protection against HER2/neu spontaneous tumor development inducing antibody and cell-mediated immune responsiveness against HER2/neu and a Th1 polarization of the immune response.     

Adjuvant chemotherapy with taxoid-containing drugs in breast cancer: soon to be expected in the Netherlands

Taxanes such as paclitaxel and docetaxel are effective cytostatic agents in metastatic breast cancer. Until now, six randomised studies with taxanes as a component of adjuvant chemotherapy for non-metastasised mammary carcinoma have been reported: four with paclitaxel and two with docetaxel. The results were more favourable in the patients treated with paclitaxel than in the controls: the absolute difference in 5-year disease-free survival was 4-5% (to be added to the 65-72% following the standard treatment) and that in total 5-year survival was 0-3% (to be added to the 77-85% following the standard treatment). The benefits of the administration of paclitaxel were not accompanied by serious myelotoxicity. Treatment with docetaxel also resulted in more patients with disease-free 5-year survival (68 vs. 75%) and total 5-year survival (81 vs. 87%). The advantage of the combination with docetaxel was most pronounced in patients with 1-3 positive nodes and those with HER 2 overexpression in their tumour. Febrile neutropenia was more common in de docetaxel group but there was no increased mortality due to toxicity. In the near future, it is expected that taxanes will play an important role in the adjuvant chemotherapy of breast cancer.     

The Cost-Utility of Sequential Adjuvant Trastuzumab in Women with Her2/Neu-Positive Breast Cancer: An Analysis Based On Updated Results from the HERA Trial

Background:  The efficacy of sequential adjuvant trastuzumab (aTZ) after chemotherapy in women with early-stage human epidermal growth factor-2 (HER2/neu)-positive breast cancer reported by the updated Herceptin Adjuvant (HERA) trial appears less favorable than originally reported. Based on these updated results, we estimated the cost-utility (CU) of sequential aTZ relative to chemotherapy alone in terms of incremental cost per quality-adjusted life-year (QALY) gained.
Methods:  A Markov model estimated incremental costs and outcomes of 12 months of aTZ after adjuvant chemotherapy in women with HER2/neu-positive breast cancer over a 25-year horizon. The model incorporated four broad health states (disease-free, local recurrence [LCR], distant recurrence [DCR], death), stratified with or without symptomatic cardiotoxicity. Baseline event rates and 3-year relative risk (RR = 0.75) were derived from the HERA trial. As the duration of the benefit remains uncertain, the analysis considered 5-year and 3-year duration of benefit in two scenarios. Costs and utility weights were from the literature. The analysis took a direct payer perspective, with costs reported in 2007 Canadian dollars. Costs and QALYs were discounted by 3% annually.
Results:  The mean CU of sequential aTZ at a 25-year horizon was $72,292 per QALY gained in the 5-year scenario and $127,862 per QALY gained in the 3-year scenario. Results were particularly sensitive to the magnitude and duration of carryover benefit.
Conclusions:  The CU of sequential aTZ is primarily dependent on the magnitude and duration of benefit. Further clinical research is required to establish the optimum sequence and duration of aTZ therapy and clarify the magnitude and duration of treatment benefit.     

Chemoradiation in nasopharyngeal carcinoma: a 6-year experience in Tehran cancer institute

To determine the addition of value of neoadjuvant, concurrent and adjuvant chemotherapy to radiation in the treatment of nasopharyngeal carcinoma with regard to the overall survival (OS) and disease free survival (DFS) within a six year period in Tehran cancer institute. Files of all patients with nasopharyngeal carcinoma treated by radiotherapy with or without concurrent chemotherapy in a curative setting in Tehran cancer institute during the period of 1999-2005 were retrospectively reviewed.. A total of 103 patients with nasopharyngeal carcinoma had been treated during the study period with radiotherapy or chemoradiotherapy in our institute. There were 29 (28.2%) females and 74 (71.8%) males. The median age at the time of radiotherapy was 47 years old (range 9-75 years). The patients were followed 2 to 76 months with a median follow-up of 14 months. Time of first recurrence after treatment was 3-44 months with a median of 10 months.. Survival in 2 groups of patients treated with radiotherapy alone or chemoradiation did not have a significant difference (P>0.1). Two-year survival in patients treated with or without adjuvant chemotherapy and had local recurrence after treatment did not have significant difference (P>0.1). Two-year survival in patients with or without local recurrence after treatment did not have significant difference (P>0.1). A beneficial affect or a survival benefit of adjuvant/neoadjuvant chemotherapy and concurrent chemoradiation was not observed in Iranian patients.     

抗MDA5抗体阳性皮肌炎患者预后影响因素研究及生存分析

目的 探究抗黑色素瘤分化相关基因5（MDA5）抗体阳性皮肌炎患者的预后影响因素及生存分析。方法 选取四川大学华西医院2018年1月至2021年9月期间确诊的178名抗MDA5抗体阳皮肌炎患者,收集相关临床资料并进行随访,根据随访期内是否死亡将入选患者分为生存组和死亡组,采用 Cox 回归分析影响患者预后的因素,Kaplan-Meier法比较在快速进展型间质性肺病、吸烟情况、乳酸脱氢酶及白蛋白水平几种因素影响下的生存情况。结果 共纳入抗MDA5抗体阳性皮肌炎患者178例,其中生存组136例,死亡组42例,两组患者平均年龄（49.56±11.63）岁。多因素Cox回归结果显示,吸烟（HR=2.23,95%CI:1.06~4.66,P=0.033）、白蛋白<30g/L（HR=2.47,95%CI:1.15~5.31,P=0.021）、乳酸脱氢酶≥400IU/L（HR=2.70,95%CI:1.26~5.76,P=0.010）、合并快速进展型间质性肺病（HR=20.56,95%CI:2.64~159.97,P=0.004）是影响抗MDA5抗体阳性皮肌炎患者预后的因素。结论 吸烟、低白蛋白血症、高乳酸脱氢酶血症、合并快速进展型间质性肺病都可能是影响抗MDA5抗体阳性皮肌炎患者不良预后的因素,应密切关注患者患病期间各因素的变化情况,积极采取治疗措施,以改善患者预后。     

环氧酶2、哺乳动物雷帕霉素靶蛋白及人类表皮生长因子受体2与胃癌预后的相关性

目的：分析环氧酶2（COX-2）、哺乳动物雷帕霉素靶蛋白（mTOR）及人类表皮生长因子受体2（HER2/neu）与胃癌患者预后的相关性,为胃癌临床诊断和治疗提供实验依据。方法应用免疫组织化学染色方法对浙江省人民医院2008年4月至2010年4月期间诊治的80例胃癌患者手术样本进行分析,比较胃癌组织与癌旁正常胃组织中COX-2、mTOR及HER2/neu蛋白的表达差异。应用Spearman秩相关分析、Kaplan-Meier法、Log-rank检验以及多因素Cox风险比例回归模型描述和推断COX-2、mTOR及HER2/neu蛋白与胃癌病理分期及预后的相关关系。结果80份胃癌癌体组织样本中COX-2、mTOR、HER2/neu蛋白的阳性表达率分别为57.5%（46份）、36.3%（29份）和63.8%（51份）,明显高于配对癌旁正常胃组织（u=5.643、3.528和4.642, P 均<0.01）;COX-2和HER2/neu 蛋白表达水平和胃癌分期之间均呈正相关（rs=0.257、u=2.284, P<0.05; rs=0.382、u=3.395,P<0.01）;COX-2和HER2/neu蛋白阳性表达患者的总体生存情况和无复发生存情况明显劣于阴性表达患者（P均<0.05）;COX-2蛋白的表达水平是胃癌总体生存时间的独立预测因素（风险比=1.643,95%CI：1.085~2.489,P<0.05）。结论 COX-2、mTOR 和 HER2/neu 蛋白均参与了胃癌的发生或发展;COX-2和HER2/neu蛋白与胃癌的病理分期和总体生存时间相关;COX-2蛋白表达可作为胃癌预后的独立预测因子。     

Trastuzumab (herceptin) for the medical treatment of breast cancer

BACKGROUND: Trastuzumab is humanized monoclonal antibody targeting her 2 neu receptor, overexpressed in 20% of breast cancers and part of the complex of Epidermal Growth Factor Receptor. AIM: To review new advances in the knowledge of the practical use of "trastuzumab (Herceptin ?)" in breast cancer. METHODS: Review of literature using medical data bases (Medline, Science direct) with the following key words: breast cancer, targeted therapy, HER2 neu, transtuzumab/herceptine RESULTS : Trastuzumab represent an important advance in breast cancer treatment with an improvement of median survival in metastatic setting and overall and disease-free survival in adjuvant setting in association with chemotherapy. Herceptin remain well tolerated with a low and rare risk of cardiac failure. CONCLUSION : Trastuzumab is a new therapeutic tool very interesting to ameliorate prognosis of breast cancer.     

云南省德宏州3103例艾滋病患者抗病毒治疗后生存分析

目的 了解云南省德宏州艾滋病患者接受国家免费抗病毒治疗后的生存情况.方法 采用回顾性研究,对德宏州2004年7月1日至2009年12月31日接受国家免费抗病毒治疗、入组抗病毒治疗时CD4+T淋巴细胞计数＜350个/μl、且年满16周岁的所有艾滋病患者进行分析.结果 共计3103例艾滋病患者开展了抗病毒治疗,平均年龄(36.0±9.9)岁,62.4%是男性,感染途径以经异性性传播为主(66.2%).病例平均随访治疗时间为21.7个月,绝大部分病例依从性＞90%,即平均每月漏服次数不足1～5次.抗病毒治疗后,第1、2、3、4、5年的累计生存率分别为0.95、0.94、0.93、0.92和0.92.Cox比例风险回归模型分析发现:在控制了年龄、性别、婚姻状况等因素的潜在混杂作用影响后,基线CD4+T淋巴细胞计数水平以及传播途径与其生存时间之间存在统计学关联.基线CD4+T淋巴细胞计数在200～350个/mm3之间死于艾滋病相关疾病的风险较基线CD4+T淋巴细胞计数＜200个/mm3的艾滋病患者低(HR=0.16,95%Cl:0.09～0.28)、经母婴传播等途径(不包括经异性性传播途径)感染HIV的患者死于艾滋病相关疾病的风险较经静脉注射毒品途径感染HIV者低(HR=0.35,95%Cl:0.13～1.00).结论 免费抗病毒治疗显著提高了艾滋病患者的生存率,较早启动抗病毒治疗有望取得更好的生存效果.     

Vaccination with novel combinations of anti-HER2/neu cytokines fusion proteins and soluble protein antigen elicits a protective immune response against HER2/neu expressing tumors

We have previously demonstrated that anti-HER2/neu IgG3-(IL-2), (IL-12)-IgG3, or IgG3-(GM-CSF) antibody fusion proteins (mono-AbFPs) elicit anti-tumor activity against murine tumors expressing HER2/neu when used as adjuvants of extracellular domain of HER2/neu (ECD(HER2)) protein vaccination. We have now studied the effect of combinations of IL-2 and IL-12 or IL-12 and GM-CSF mono-AbFPs during vaccination with ECD(HER2). In addition, we developed two novel anti-HER2/neu IgG3-cytokine fusion proteins in which IL-2 and IL-12 or IL-12 and GM-CSF were fused to the same IgG3 molecule (bi-AbFPs). (IL-12)-IgG3-(IL-2) and (IL-12)-IgG3-(GM-CSF) were properly assembled and retained both cytokine activity and the ability to bind antigen. Vaccination of mice with ECD(HER2) and a combination of cytokines as either bi-AbFPs or two mono-AbFPs activated both Thl and Th2 immune responses and resulted in significant protection against challenge with a HER2/neu expressing tumor. Our results suggest that this approach will be effective in the prevention and/or treatment of HER2/neu expressing tumors.     

Differential influence of dietary soy intake on the risk of breast cancer recurrence related to HER2 status

The effects of soy products and isoflavone on breast cancer recurrence were compared according to receptor status including epidermal growth factor receptor-2 (HER2) with 339 Korean women. Dietary intake of soy foods was assessed using a validated food frequency questionnaire with 103 food items. Twenty-five patients experienced breast cancer recurrence, 17 patients were HER2 negative, and 8 patients were HER2 positive. Legume intake (mostly from black soybeans) was inversely associated with the risk of breast cancer recurrence in HER2 negative cancer patients (HR: 0.27, 95% CI: 0.13-0.57, P for trend < 0.01), whereas legume intake was positively associated in HER2 positive cancer patients (P for trend = 0.02). In HER2 negative cancer patients, isoflavone was inversely associated with breast cancer recurrence (HR: 0.23, 95% CI: 0.06-0.89; P for trend = 0.01). Total soy intake was not associated with an increased risk of cancer recurrence. In conclusion, overall soy food intake might not affect the risk of cancer recurrence, but high intake of soy isoflavones increased the risk of cancer recurrence in HER2-positive breast cancer patients. However, further research is needed to confirm these results due to the small number of cancer recurrence events.     

Cost-effectiveness analysis of strategies for HER2 testing of breast cancer patients in France

OBJECTIVES: A cost-effectiveness analysis was conducted comparing diagnostic strategies for determining the HER2 status of invasive breast carcinomas, as an indication for trastuzumab at metastatic relapse. METHODS: A decision tree compared five strategies distinguished by (i) the use of immunohistochemical (IHC) and/or fluorescent in situ hybridization (FISH) techniques, and (ii) the test schedule (at initial diagnosis or metastatic relapse). Most cost and effectiveness data came from a French multicentric study of 2,045 patients from eight hospitals. We were not able to select final criteria for trastuzumab effectiveness, because published data rely on IHC techniques not used in France (i.e., HercepTest). We, therefore, selected two intermediate criteria for inappropriate treatment at relapse, that is, patients with HER2-amplified tumors not receiving trastuzumab (Criterion 1) and HER2-nonamplified tumors improperly treated with trastuzumab (Criterion 2). Sensitivity analyses were then performed to assess the robustness of the results to (i) discount rate, (ii) cost of FISH, and (iii) tissue fixation technique. RESULTS: The strategy using IHC at diagnosis was dominated by the four other strategies. Among these approaches, the only efficient strategy for both criteria was IHC used alone at metastatic relapse; strategies using FISH, or IHC followed by FISH on IHC2+ cases were efficient for Criterion 1, whereas IHC followed by FISH on IHC2+ and 3+ cases was efficient for Criterion 2. CONCLUSIONS: Determining HER2 status at diagnosis, as an indication for trastuzumab at metastatic relapse, incurs substantial incremental costs, which do not appear to be justified. No other strategy can be excluded at first.     

Combination of epitope-optimized DNA vaccination and passive infusion of monoclonal antibody against HER2/neu leads to breast tumor regression in mice

HER2/neu is an oncogene amplified and over-expressed in 20-30% of breast adenocarcinomas. Treatment with the humanized monoclonal antibody trastuzumab has shown efficacy in combination with cytotoxic agents, although resistance occurs over time. Novel approaches are needed to further increase antibody efficacy. In this study, we provide evidence in a mouse breast cancer therapeutic tumor model that the combination of active immunization with a modified HER2/neu DNA vaccine and passive infusion of an anti-HER2/neu monoclonal antibody leads to significant regression of established tumors. Our data indicate that combination therapy with a HER2/neu DNA vaccine and trastuzumab may have clinical activity in breast cancer patients.     

曲妥珠单抗辅助治疗早期HER2阳性乳腺癌的药物经济学评价

目的:从医疗保障部门角度对曲妥珠单抗辅助治疗早期HER2阳性乳腺癌进行药物经济学评价,为推进乳腺癌规范诊疗和医保政策制定提供依据和参考。方法:基于HERA临床试验,运用Markov模型模拟乳腺癌的发展,比较早期乳腺癌曲妥珠单抗1年辅助治疗组与观察组的成本效用,并进行经济学分析。结果:若采用曲妥珠单抗辅助治疗,患者的期望生存年、质量调整生命年将分别延长4.30年、2.86年,延长1年所需增加的医疗费用分别为96 334元、144 936元。结论:在湖北省使用曲妥珠单抗辅助治疗早期HER2阳性乳腺癌具有较好的成本效用,湖北省或经济发展水平相当及较高的省市医保部门可以考虑将曲妥珠单抗纳入到医保目录。     

对比HER-2及性激素受体在乳腺癌原发灶及配对复发转移灶之间的表达

目的研究ER、PR、HER-2受体表达在乳腺癌原发灶和复发转移灶之间是否存在着差异及其相应的临床意义。方法采用免疫组织化学染色方法检测42例复发转移乳腺癌病例中ER、PR、HER-2受体在原发灶及复发转移灶之间的表达差异。结果ER和HER-2受体在原发灶及复发转移灶表达的不一致率分别为28．6％（P〈0．05）和38．1％（0．005〈P〈0．01）．而PR的表达不一致率为33．3％,统计学上无显著性差异;原发灶ER表达缺失及HER-2受体过表达具有良好的预测价值。结论进展期乳腺癌中,原发灶同复发转移灶性激素受体及HER-2受体表达存在显著性差异,在临床实践中应该考虑这些差别。     

Experience and results of acute lymphoblastic leukaemia treatment in children between 1989-2005 in Navarre

BACKGROUND. The determination of prognostic factors in acute lymphoblastic leukaemia (ALL) is increasingly important in establishing a correct treatment. We analyse the overall survival (OS), event free survival (EFS) and prognostic factors in our 16 years experience of treating acute lymphoblastic leukaemia. METHODS. We performed univariate and multivariate analyses of the prognostic factors we considered most significant in our serie of patients. RESULTS. From January 1989 to December 2005, 50 cases of ALL were reported in 58 patients with LA. We analysed a subgroup of 41 patients with LLA as they were included in standard protocols. In this group the EFS was 78% and OS 87.8%. Inmunophenotype is a predictor of prognosis when we compare Common with Others, with a HR of 13.82 (CI95%: 1.019-166.008) p<0.05; Protocol of Treatment of the Paediatric Haematology Oncology Society (SHOP) (94-99/89) with HR of 0.065 (CI95%: 0.005-0.008) p<0.02; and Age (>120 months/12-120 months) with a HR of 13.82 (CI95%: 0.58-329.48) p=0.1. CONCLUSIONS. The OS in our series is similar to that reported in the literature. Inmunophenotype and protocols of treatment are the most significant prognostic factors.     

Surgical treatment of early stage cervical carcinoma at Leids University Medical Center, 1984-1996: depth of invasion, number and bilaterality of metastatic lymph nodes prognostic for recurrence

OBJECTIVE: To analyse local tumour parameters of early cervical cancer that might be of prognostic significance for tumour relapse in the pelvis. DESIGN: Retrospective. METHOD: Data were collected from 308 patients who underwent radical hysterectomy and pelvic lymphadenectomy in the years 1984-1996 in the Leiden University Medical Centre, the Netherlands. Treatment policies and operating staff were the same during the study period. The existence of relapse was studied by physical, gynaecological, laboratory and, if indicated, radiological examination. RESULTS: Data on 294 patients were available for analysis. Their mean age was 45 years (range: 21-82). Postoperative radiation treatment was given to 119 patients (40%). Mean follow-up duration was 36 months (range: 1-136). Recurrences had developed in 46 patients (15.6%), 29 of whom had died. The calculated overall 5-year survival rate was 83%; 91% for those with negative and 53% for those with positive pelvic nodes. The calculated recurrence-free-5-year survival rate was 75% for the entire group, 83% for the patients without and 47% for those with lymph node metastases. When more than one lymph node region was affected, 5-year disease free survival was 19% and when lymph node metastasis occurred bilaterally, it was 22%. Multivariate analysis revealed that lymph node involvement (hazard ratio: 4.4), parametrial involvement (5.5), tumour size > 30 mm (4.6) and depth of invasion > 10 mm (5.1) were independent factors of prognostic significance for disease free survival. The current indications for adjuvant treatment might be extended with infiltration depth. The number and the bilaterality, if any, of affected lymph node stations might be indication for additional adjuvant therapy.     

Survival from breast cancer in relation to access to tertiary healthcare, body mass index, tumor characteristics and treatment: a Hellenic Cooperative Oncology Group (HeCOG) study

Apart from tumour, treatment and patient characteristics at diagnosis, access to healthcare delivery may as well play a significant role in breast cancer prognosis. This study aimed to assess the additional impact exerted on survival by travel burden—a surrogate indicator of limited access to healthcare- expressed as geographical distance and/or time needed to reach the tertiary healthcare center from the patient’s residence. Between 1997 and 2005, 2,789 women participated in therapeutic clinical trials conducted by the Hellenic Cooperative Oncology Group. The effect of geographical distance and travel time between patient’s residence and treating hospital on survival was estimated using Cox proportional hazards regression adjusting for age, menopausal status, tumour size/grade, positive nodes (number), hormonal receptor status, HER2 overexpression, surgery type/treatment protocol as well as for body mass index >30?kg/m². More aggressive tumour features, older treatment protocols and modifiable patient characteristics, such as obesity (HR: 1.27) adversely impacted on breast cancer survival. In addition, less studied indicators of access to healthcare, such as geographic distance >350?km and travel time >4?h were independently and significantly associated with worse outcomes (HR?=?1.43 and 1.34 respectively). In conclusion, to address inequalities in breast cancer survival, improvements in access to healthcare services related to increased travel burden especially for patients of lower socioeconomic status should be considered, more than ever at times of financial crisis and independently of already known modifiable patient characteristics.