Mammakarzinom bei alten Patientinnen

Most clinical trials using adjuvant chemotherapy for breast cancer set an age limit of 65 or 70 years for the recruitment of patients. Therefore, little is known about the effect of therapy in elderly patients. Physicians are still constrained to confer knowledge to elderly patients that has been acquired in clinical trials on postmenopausal women of younger ages. In the particular situation of elderly patients, comorbidity conditions have to be considered and balanced with the potential achievable benefit. Analyses of databases have shown that based on these considerations elderly patients are often withheld from chemotherapy. Adjuvant chemotherapy is not indicated in elderly patients without lymph node involvement and with endocrine responsive disease. However, chemotherapy should be applied more often in elderly patients with lymph node involvement and without endocrine responsive disease. Adjuvant radiotherapy may not be indicated for “low risk” tumors (T1–2N0) in women aged 70 years and older, but can be of benefit for patients with “high risk” tumors (T3–T4 or N+), if poor health status or comorbidity are not present.     

淋巴结转移数和淋巴结转移率与乳腺癌预后关系的分析比较

  目的  探讨淋巴结转移率(lymph node ratio, LNR)是否能更优于淋巴结转移数(positive lymph nodes, PLN), 用于评价乳腺癌术后患者的复发风险和总生存时间。  方法  回顾性分析1089例淋巴结清扫数目为10枚或以上、术后经病理证实淋巴结转移阳性的原发性浸润性乳腺癌患者临床病理资料。  结果  单因素生存分析, 肿瘤大小分期, 组织学分级、ER/PR/HER-2状态、PLN、LNR、切检淋巴结总数、结外软组织侵犯、辅助治疗与患者RFS(relapse free survival, RFS)、OS(overall survival, OS)均具有明显的相关性(P < 0.05);多因素生存分析, 当PLN和LNR作为协变量分别进入Cox比例风险模型时, PLN和LNR均为患者RFS和OS的独立预测指标(P < 0.001);当PLN和LNR作为协变量同时进入Cox比例风险模型时, LNR依然是患者RFS和OS的独立预测指标(RFS: P < 0.001.OS: P=0.001), 而PLN不再是其独立预测指标(RFS: P=0.944, 0S: P=0.315)。  结论  相对于PLN而言, LNR能更好的评价乳腺癌术后患者的复发风险和总生存时间, 为乳腺癌危险度分级和临床医生制定辅助治疗方案提供更有力的参考依据。      

Direct comparisons of adjuvant endocrine therapy, chemotherapy, and chemoendocrine therapy for operable breast cancer patients stratified by estrogen receptor and menopausal status

Based on estrogen receptor (ER) and menopausal status, operable breast cancer (UICC stage I, II, III-a) patients were randomized for adjuvant endocrine therapy, chemotherapy, and chemoendocrine therapy, and the effects on the relapse-free survival (RFS) and overall survival (OS) were compared. Tamoxifen (TAM) 20 mg/day was administered orally for 2 years after mastectomy as an adjuvant endocrine therapy in postmenopausal patients. In premenopausal patients, oophorectomy (OVEX) was performed before TAM administration. In the chemotherapy arm (CHEM), patients were given 0.06 mg/kg of body weight of mitomycin C (MMC) intravenously, followed by an oral administration of cyclophosphamide (CPA) 100 mg/day in an administration of a 3-month period and a 3-month intermission. This 6-month schedule was repeated 4 times in 2 years. The chemoendocrine arm (CHEM + TAM) was composed of TAM with MMC + CPA chemotherapy. The patients were randomized according to ER and menopausal status. ER-positive patients were randomized to three arms: OVEX ± TAM, CHEM, and CHEM + TAM. For ER-negative patients there were two arms: CHEM and CHEM + TAM. 1579 patients entered the trial between September 1978 and December 1991, with median follow-up of 8.2 years. In ER-positive, premenopausal patients, there were no significant differences in RFS or OS among OVEX ± TAM, MMC + CPA, TAM + MMC + CPA arms. On the contrary, in ER-positive, postmenopausal patients, the chemoendocrine therapy showed a significantly higher RFS (p = 0.0400) and OS (p=0.0187) as compared with TAM to chemotherapy alone. There were no significant differences in RFS or OS by addition of TAM on the chemotherapy, in both pre- and post-menopausal ER-negative patients. It was concluded that in ER-positive premenopausal breast cancer, endocrine therapy alone may be equivalent in prolonging RFS and OS to chemotherapy or chemoendocrine therapy, and that ER-positive postmenopausal breast cancer may be better controlled with the combination of TAM and chemotherapy, as compared to TAM or chemotherapy alone. The importance of stratification of operable breast cancer by ER and menopausal status, as well as the direct comparisons of different treatments, were stressed.This revised version was published online in October 2005 with corrections to the Cover Date.     

老年乳腺癌患者的临床特点及治疗模式的研究

目的：总结老年乳腺癌患者的临床特点,分析其对所采取治疗模式的影响。方法根据患者所处的年龄阶段（60~69岁和≥70岁）将178例接受治疗的老年乳腺癌患者分为A组（103例）和B组（75例）。分析两组患者所采取的治疗方式、疗效及不良反应等差异。结果 A组进行术后辅助化疗的患者比例明显高于B组,差异有统计学意义（P<0.05）;年龄在60~69岁、雌性激素受体阴性及淋巴结转移阳性是术后采取辅助化疗的影响因素（P<0.05）;A组的总有效率高于B组,但差异无统计学意义（P>0.05）;两组均无严重不良反应发生。结论年龄在60~69岁的乳腺癌患者术后宜采取辅助化疗,≥70岁的乳腺癌患者可采取内分泌辅助治疗。     

118例小肿块多腋窝淋巴结转移乳腺癌患者的临床特征和预后分析

目的分析小肿块多腋窝淋巴结转移(肿块直径≤2 cm、腋窝淋巴结转移≥4个)乳腺癌患者的临床特征和预后。方法1993年1月至2003年12月我院共收治小肿块多腋窝淋巴结转移乳腺癌患者118例,对其临床病理特征、辅助治疗进行分析,以发现相关的预后因素。结果全组患者的5年总生存率为75.0%。腋窝淋巴结转移4～9个及≥10个者的5年生存率分别为89.5%和59.8%(P=0.009),术后化疗患者与未化疗患者的5年生存率分别为82.1%和53.3%(P=0.001),术后内分泌治疗者与未行内分泌治疗者的5年生存率分别为89.2%和61.9%(P=0.001)。单因素Kaplan-Merier生存分析显示,肿瘤分期、术后化疗和内分泌治疗是影响患者预后的重要因素。Cox多因素预后分析显示,肿瘤分期、术后化疗和内分泌治疗是影响患者预后的独立因素。结论小肿块多腋窝淋巴结转移的乳腺癌患者具有易于转移的趋势,患者预后较差,尤其是腋窝淋巴结转移≥10个的患者;肿瘤分期、辅助化疗和内分泌治疗是影响患者预后的独立因素;合理的综合治疗有可能改善小肿块多腋窝淋巴结转移乳腺癌患者的预后。     

２９３例乳腺癌患者术后预后因素分析

目的：探讨２９３例乳腺癌患者月经情况、术后Ｔ分期、Ｎ分期、受体、术后放疗、化疗及内分泌治疗等因素对患者无病生存时间及总生存时间的影响。方法：收集我院２００２～２００６年２９３例乳腺癌患者术后的完整随访资料,选择可能对乳腺癌术后患者预后产生影响的非重复特征因素,包括月经情况、术后病理的Ｔ分期、Ｎ分期、受体的免疫组化分型、术后放疗、化疗及内分泌治疗,采用Ｃｏｘ风险回归模型分析影响无复发生存率（ＲＦＳ）和总生存率（ＯＳ）的预后因素。对具有统计学意义的独立预后因素进行分层分析及Ｋａｐｌａｎ Ｍｅｉｅｒ生存曲线分析。结果：本组病例中Ｎ分期是影响患者ＲＦＳ及ＯＳ的独立因素,相对危险度（ＯＲ）分别为１.４５３（９５％ＣＩ：１.０９６～１.９２６,Ｐ＜０.０１）、１.４５８（９５％ＣＩ：１.０９９～１.９９３,Ｐ＜０.０１）。对Ｎ分期进行分层分析及Ｋａｐｌａｎ Ｍｅｉｅｒ生存曲线分析表明,Ｎ０期患者的ＲＦＳ及ＯＳ优于Ｎ１～Ｎ３期患者（Ｐ＜０.０５）,而Ｎ１～Ｎ３期患者之间ＲＦＳ及ＯＳ无差异（Ｐ＞０.０５）。结论：乳腺癌术后患者Ｎ分期与患者的预后有关,淋巴结阴性患者的预后好于淋巴结阳性患者预后,建议对淋巴结阳性患者加强术后辅助治疗。     

Prognosis of node-positive breast cancer patients who underwent parasternal lymph node biopsy during surgery followed by doxorubicin- or mitoxantrone-containing adjuvant chemotherapy

The authors examined the survival rates of 60 patients with breast cancer who underwent parasternal lymph node biopsy during surgery with axillary lymph node dissection and had histologically confirmed axillary node metastasis followed by adjuvant doxorubicin- or mitoxantrone-containing combination chemotherapy to ascertain whether administration of anthracycline or its analogue improved the prognosis of both axillary and parasternal node-positive patients. The overall survival rate (OS) for the parasternal node-positive patients (n=13, 21.7%) was 30.6%, and relapse-free survival rate (RFS) fell to 0% at the 104-month follow-up. Although the survival rate for all axillary node-positive patients was similar to those in previous reports, the OS and RFS for both axillary and parasternal node-positive patients were significantly worse than that for axillary node-positive and parasternal node-negative patients, despite treatment with adjuvant doxorubicin- or mitoxantrone-containing combination chemotherapy. Other intensive adjuvant treatment strategies are needed to reduce distant metastases for high-risk breast cancer patients having both axillary and parasternal nodes positive.     

Prognosis of Node-Positive Breast Cancer Patients Who Underwent Parasternal Lymph Node Biopsy During Surgery Followed by Doxorubicin- or Mitoxantrone-Containing Adjuvant Chemotherapy

Abstract

The authors examined the survival rates of 60 patients with breast cancer who underwent parasternal lymph node biopsy during surgery with axillary lymph node dissection and had histologically confirmed axillary node metastasis followed by adjuvant doxorubicin- or mitoxantrone-containing combination chemotherapy to ascertain whether administration of anthracycline or its analogue improved the prognosis of both axillary and parasternal node-positive patients. The overall survival rate (OS) for the parasternal node-positive patients (n=13, 21.7%) was 30.6%, and relapse-free survival rate (RFS) fell to 0% at the 104-month follow-up. Although the survival rate for all axillary node-positive patients was similar to those in previous reports, the OS and RFS for both axillary and parasternal node-positive patients were significantly worse than that for axillary node-positive and parasternal node-negative patients, despite treatment with adjuvant doxorubicin- or mitoxantrone-containing combination chemotherapy. Other intensive adjuvant treatment strategies are needed to reduce distant metastases for high-risk breast cancer patients having both axillary and parasternal nodes positive.     

A randomized study of adjuvant treatments for operable breast cancer patients stratified by estrogen receptor and menopausal status

According to estrogen receptor (ER) and menopausal status, operable breast cancer patients were randomized for adjuvant endocrine therapy with tamoxifen (TAM) in premenopausal patients, after oophorectomy (OVEX), chemotherapy, CHEM (mitomycin C+ oral cyclophosphamide), or chemo-endocrine therapy (TAM + CHEM). Some 1579 patients were entered in the trial between 9, 1978 and 12, 1991, with a median follow-up of 10 years. In ER-positive, premenopausal patients there were no significant differences in relapse-free (RFS) or overall survival (OS) among the OVEX + TAM, CHEM, and CHEM + TAM arms. On the contrary, in ER-positive, post-menopausal patients, the chemoendocrine therapy showed a significantly better OS (p = 0.0254) with a trend of better RFS (p = 0.0674), as compared with TAM or CHEM groups. ER-negative, premenopausal patients showed no significant differences in RFS or OS between CHEM and CHEM + TAM arms. In ER-negative, postmenopausal patients, there was a non-significantly better RFS (p = 0.0888) and a significantly better OS (p = 0.0332) in CHEM + TAM group than in the CHEM alone group. These results suggest that ER and menopausal status are important criteria to select early breast cancer patients for adjuvant treatments.     

65岁以上中国老年女性原发性乳腺癌临床病理特征及治疗分析：多中心10年回顾性研究

[目的]研究65岁以上老年女性原发性乳腺癌的风险暴露因素、临床病理特征以及治疗特征,为老年女性乳腺癌的诊治提供依据.[方法]回顾性分析全国7个不同地区具有代表性的7家医院收集的4211例乳腺癌患者信息,将65岁以上患者作为研究对象(老年组),50～64岁年龄组作为对照组.统计学方法为卡方检验和Fisher精确检验,P＜0.05具有统计学意义.[结果]65岁以上老年乳腺癌患者占同期乳腺癌患者的8.33％(351/4211).平均诊断年龄和平均绝经年龄分别为70.2岁(65～86岁)和49.59岁(32～58岁).与对照组相比,老年组具有以下特征:以体力工作、生育大于一胎、低学历、结婚早和初次生育年龄早者显著;临床病理特征方面,老年患者区域淋巴结转移少、分期早(即更多的0+Ⅰ+Ⅱ期患者)、激素受体阳性率高、Hey2低表达、Her-2亚型和三阴性亚型少.在侵袭性治疗方面,老年患者较少接受改良根治术、保乳术、放疗、化疗,更多的是接受乳腺单纯切除术.两组间内分泌治疗无显著差异.[结论]老年乳腺癌患者有较好的临床病理特征和生物学行为;接受侵袭性治疗少;内分泌治疗需要加强.     

Correlation of vascular endothelial growth factor content with recurrences, survival, and first relapse site in primary node-positive breast carcinoma after adjuvant treatment.

PURPOSE: To determine the predictive value of vascular endothelial growth factor (VEGF) for relapse-free survival (RFS) and overall survival (OS) in primary node-positive breast cancer (NPBC) after adjuvant endocrine treatment or adjuvant chemotherapy. MATERIALS AND METHODS: VEGF was quantitatively measured in tumor cytosols from 362 consecutive patients with primary NPBC using an enzyme immunoassay for human VEGF(165). Adjuvant treatment was given to all patients, either as endocrine therapy (n = 250) or chemotherapy (n = 112). The median follow-up time was 56 months. RESULTS: Univariate analysis showed VEGF to be a significant predictor of RFS (P =.0289) and OS (P =.0004) in the total patient population and in patients who received adjuvant endocrine treatment (RFS, P =.0238; OS, P =.0121). In the group of patients who received adjuvant chemotherapy, no significant difference was seen in RFS, but a difference was seen in OS (P =.0235). Patients with bone recurrences tended to have lower VEGF expression (median, 2.17 pg/microg DNA) than patients with visceral metastasis (4.41 pg/microg), brain metastasis (8.29 pg/microg), or soft tissue recurrences (3.16 pg/microg). Multivariate analysis showed nodal status (P =.0004), estrogen receptor (ER) status (P <.0001), and tumor size (P =.0085) to be independent predictors of RFS. VEGF was found to be an independent predictor of OS (P =.0170; relative risk [RR] = 1.82), as were ER (P <.0001; RR = 5.19) and nodal status (P =.0002; RR = 2.58). For patients receiving adjuvant endocrine treatment, multivariate analysis showed VEGF content to be an independent predictor of OS (P =.0420; RR = 1.90) but not of RFS. CONCLUSION: The results suggest that VEGF(165) content in tumor cytosols is a predictor of RFS and OS in primary NPBC. VEGF content might also predict outcome after adjuvant endocrine treatment, but further studies in a prospective setting with homologous treatments are required.     

青年老年乳腺癌临床病理资料与预后的探讨

目的 探讨青年和老年女性乳腺癌患者的临床特征与预后的关系。方法回顾性研究2005年1月至2007年1月新疆肿瘤医院和新疆奎屯农七师医院收治的83例青年女性乳腺癌患者（≤35岁）及92例老年女性乳腺癌（≥65岁）的临床和病理资料,比较无瘤生存率（DFS）的差异。两组临床数据（淋巴结转移、浸润性导管癌、ER、PR、C—erbB-2、P53、手术方式、是否放、化疗、内分泌治疗）比较采用）（。检验;肿瘤直径、肿瘤分期采用秩和检验;生存分析采用Kaplan．Meier法,以P〈0．05为差异有统计学意义。结果两组患者在肿块大小、腋窝淋巴结转移情况、ER、C—erbB-2的差异均有统计学意义（P〈0．05）;两组患者的病理类型、PR、P53比较差异无统计学意义（P〉0．05）;两组患者治疗方式无明显差别,青年组5年的DFS低于老年,且差异具有统计学意义（P〈0．05）。结论青年乳腺癌恶性程度高并且预后差,而老年乳腺癌恶性程度较低,预后较好。     

Prognosis of a series of 763 consecutive node-negative invasive breast cancer patients without adjuvant therapy: analysis of clinicopathological prognostic factor.

BACKGROUND AND OBJECTIVES: The objectives of this study were to confirm the favorable outcome of Japanese invasive breast cancer patients without lymph node metastasis, after treatment with surgery alone, and to evaluate clinicopathological prognostic factors in this population. METHODS: The subjects were 763 consecutive node-negative invasive breast cancer patients who underwent surgery without adjuvant therapies between 1988 and 1993 at our hospital. Disease-free survival (DFS) and overall survival (OS) rates were analyzed by clinicopathological factors. RESULTS: The median age of the patients at surgery was 52 years and the median follow-up period of patients was 74 months. At 5 years, the respective DFS and OS rates of all patients were 90.8% and 93.9%. Patients with a pathological tumor size of invasive component of more than 2 cm (319 patients) had a significantly lower DFS than those with tumors measuring 2 cm or less (361 patients) (P = 0.045). Patients with positive hormone receptor status (280 patients) (estrogen and/or progesterone receptor positive) tended to have a better OS than those negative for both hormone receptors (92 patients) (P = 0.078). Meanwhile, patients with tumors of histological grade 3 (328 patients) had a much poorer prognosis than those with tumors of histological grade 1 or 2 (413 patients) (P = 0.008 for OS and P = 0.042 for DFS). The respective 5-year DFS and OS rates of patients with histological grade 3 tumors larger than 2 cm in pathological tumor size of invasive component (195 patients) were 85.5% and 87.6%, indicating that these node-negative patients form a high risk group. CONCLUSIONS: Japanese invasive breast cancer patients without lymph node metastasis tended to show a survival advantage compared with their Caucasian counterparts. Histological grade was the most useful prognostic factor in this population.     

70岁以上老年女性乳腺癌患者的特点和预后分析

目的 分析70岁以上老年女性乳腺癌患者的临床及病理特点、生存率和影响预后的因素。方法收集1980年1月至2003年12月收治的280例70岁以上老年乳腺癌患者的临床资料,观察患者长期生存率,分析其临床特点及影响预后的因素。结果全组280例老年乳腺癌占同期收治乳腺癌患者的2．9％。92．5％的患者以乳房肿块为首发症状,中位就诊时间为4个月,58．9％的患者合并有其他疾病。主要病理类型为浸润性导管癌（74．3％）。免疫组化分析显示,雌、孕激素受体阳性者占72．9％。全组患者5、10年总生存率分别为69．9％和40．6％。单因素分析显示,肿瘤大小、淋巴结状态、分期、脉管瘤栓和内分泌治疗是影响预后的因素;多因素分析显示,淋巴结状态和脉管瘤栓是影响预后的独立因素。结论老年乳腺癌具有独特的临床和病理特点,手术和内分泌治疗是主要和有效的治疗方式。影响预后的独立因素是淋巴结状态和脉管瘤栓。     

Prognostic value of lymph node ratio in poor prognosis node‐positive breast cancer patients in Saudi Arabia

Aim: Women in Saudi Arabia develop breast cancer at a young age with high prevalence of poor prognostic features. Because of such features, it is necessary to examine prognostic factors in this population. One such factor is the prognostic role of lymph node ratio (LNR). Methods: We performed retrospective analyses of patients with invasive non‐metastatic breast cancer who underwent axillary lymph node dissection and had one or more positive axillary lymph nodes. Results: Two hundred and seventeen patients were considered eligible for the analysis. The median age was 46 years. At a median follow‐up of 39.8 months, the median disease‐free survival (DFS) was 67.3 months (95% CI, 50.4 to 84.3 months). Neither the classification of patients based on positive lymph node (pN) staging system, nor the absolute number of pN prognosticated DFS. Conversely, age ≤ 35 years at diagnosis, grade 3 tumors and the intermediate (>0.20 to ≤0.65) and high (>0.65) LNR categories were the only variables that were independently associated with adverse DFS. Using these variables in a prognostic model allowed the classification of patients into three distinctive risk strata. The overall survival (OS) in this series was 92.5 months (95% CI, 92.1–92.6). Only ER negative tumor adversely influenced OS. Conclusion: Analysis of survival outcome of mostly young patients with early breast cancer identified adverse prognostic variables affecting DFS. If the utility of the derived model including LNR is proven in a larger patient population, it may replace the use of absolute number of positive axillary lymph nodes.     

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.     

Cyclin-E is a strong predictor of endocrine therapy failure in human breast cancer

Recently, cyclin-E was reported to be the most prominent prognostic factor for breast cancer outcome described so far, even surpassing axillary nodal involvement. Earlier studies on the prognostic value of cyclin-E in breast cancer, however, yielded heterogeneous results. Therefore, we set out to confirm and extend these results by quantitative Taqman RT-PCR of cyclin-E levels in 277 resectable breast cancers. Cyclin-E levels were not associated with relapse-free survival (RFS) or overall survival (OS) in the total cohort of patients, or in the subset of patients without involved lymph nodes that were not treated with adjuvant systemic therapy. Besides several classical clinicopathological factors, the interaction between cyclin-E and adjuvant endocrine therapy (P=0.01, HR=3.04, 95% CI: 1.30-7.09) was found to contribute significantly in multivariate analyses. Cyclin-E levels were associated with poor RFS specifically in patients treated with adjuvant endocrine therapy (n=108, P=0.001, HR=4.01, 95% CI: 1.76-9.12), independent of estrogen receptor status. In conclusion, cyclin-E is not a pure prognostic factor in breast cancer, but rather a predictor of failure of endocrine therapy. Differences in literature on the presumed prognostic value of cyclin-E may be due to differences in treatment. Assessment of cyclin-E levels can aid in improving adjuvant treatment selection.     

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.     

Worse survival for TP53 (p53)-mutated breast cancer patients receiving adjuvant CMF.

BACKGROUND: TP53 has been described as a prognostic factor in many malignancies, including breast cancer. Whether it also might be a predictive factor with reference to chemo- and endocrine therapy is more controversial. PATIENTS AND METHODS: We investigated relapse-free (RFS), breast cancer-corrected (BCCS) and overall survival (OS) related to TP53 status in node-positive breast cancer patients that had received polychemotherapy [cyclophosphamide, methotrexate, 5-fluorouracil (CMF)] and/or endocrine therapy (tamoxifen). Sequence analyses of the whole TP53 coding region was performed in 376 patients operated on for primary breast cancer with axillary lymph node metastases between 1984 and 1989 (median follow-up time 84 months). RESULTS: TP53 mutations were found in 105 patients (28%). We found 90 (82%) of the 110 mutations in the more frequently analysed exons 5-8, while the other 20 (18%) were located in exons 3-4 and 9-10, respectively. Univariate analyses showed TP53 to be a significant prognostic factor with regard to RFS, BCCS and OS in patients who received adjuvant CMF. CONCLUSIONS: TP53 mutations might induce resistance to certain modalities of breast cancer therapy. Sequence-determined TP53 mutation was of negative prognostic value in the total patient population and in the CMF treated patients.     

Validation and problems of St-Gallen recommendations of adjuvant therapy for node-negative invasive breast cancer in Japanese patients.

BACKGROUND: The objectives of this study were to confirm the favorable outcome of invasive breast cancer in Japanese patients without lymph node metastasis who did not receive adjuvant therapies and to validate the St-Gallen recommendations in this population. METHODS: The subjects were a consecutive series of 920 node-negative invasive breast cancer patients who underwent surgery between 1987 and 1994 at our hospital. These patients did not receive adjuvant chemotherapy. Ten-year disease-free (DFS) and overall survival (OS) rates were analyzed by the St-Gallen risk categories (Minimal/Low, Intermediate, High). RESULTS: The median age of the patients at surgery was 52 years and the median follow-up period of patients was 10.2 years. At 10 years, the respective DFS and OS rates of all patients were 84.6 and 86.7%. The DFS and OS of patients in the Minimal/Low risk category (25 patients) both showed 100%. The DFS and OS of patients in the Intermediate risk category (356 patients) showed 92.0 and 93.1%, respectively. The DFS and OS of patients in the High risk category (539 patients) showed 79.4 and 82.2%, respectively, indicating a significant difference between those in the Minimal/Intermediate risk category (381 patients) (p < 0.001, p < 0.001, respectively). The DFS and OS of patients who had one pathological lymph node metastasis (775 patients) showed 72.7 and 75.2%, respectively, which indicated a non-significant difference between those in the High risk category (381 patients) (p = 0.10). These data support the validation of adjuvant therapy for high-risk node-negative breast cancers in Japanese patients. However, quality control is needed to define the histological grade included in the risk categories. CONCLUSION: Japanese patients with invasive breast cancer without lymph node metastasis showed a survival advantage compared with their Caucasian counterparts. However, patients in the High risk group as defined by St-Gallen recommendations should be indicated for adjuvant therapy.