多西紫杉醇联合表柔比星新辅助化疗治疗老年局部晚期乳腺癌30例

[目的]观察多两紫杉醇联合表柔比星（TE）新辅助化疗治疗老年局部晚期乳腺癌（LABC）的客观缓解率、手术切除率及毒副反应。[方法]2005年10月至2008年8月,30例经空芯针活检组织学诊断证实的老年LABC行TE方案新辅助化疗,Ⅲa期17例,Ⅲb期11例,Ⅲc期2例,中位年龄74岁;化疗剂量为：多西紫杉醇75mg/m2,d1静滴,表柔比星60mg／m2,d1静滴,每3周为1个周期：2个周期TE方案之后对病灶进行首次评估,以决定是否再给予1～2个周期TE后再接受手术或放射治疗．[结果]30例患者接受2～4个周期TE方案的新辅助化疗,25例降低了临床分期,降期率为75．0％（25／30）：临床完全缓解率（CCR）及临床部分缓解率（CPR）分别为23．3%（7／30）、53.3％（16／30）;手术切除率为96．7％（29／30）。常见毒副反应有：中性粒细胞减少症、轻中度脱发、恶心、呕吐、体液潴留、肌肉关节疼痛等。Ⅲ、Ⅳ度中性粒细胞减少症分别为23．3％（7／30）和3.3％（1／30）。[结论]TE方案新辅助化疗治疗老年LABC患者是安全有效的,可以降低临床分期,提高患者术后的生活质量。     

乳腺癌ＣＯＸ-２表达与紫杉醇脂质体联合表柔比星新辅助化疗疗效关系的研究

目的　研究紫杉醇脂质体联合表柔比星新辅助化疗治疗乳腺癌前后ＣＯＸ-２表达的变化及其与新辅助化疗疗效的关系。方法　对４１例乳腺癌患者行新辅助化疗,方案为：表柔比星８０ｍｇ／ｍ^２,静脉注射,ｄ_１;紫杉醇脂质体１３５ｍｇ／ｍ^２,静脉滴注,３ｈ,ｄ_２,３周为１周期,共２～６个周期。免疫组织化学法检测新辅助化疗前后肿瘤组织ＣＯＸ-２的表达。结果　４１例乳腺癌患者新辅助化疗的有效率为７０.７％（２９／４１）。新辅助化疗前ＣＯＸ-２表达阳性率为６３.４％,化疗后为４３.９％ （Ｐ＜０.０５）。新辅助化疗前ＣＯＸ-２表达阳性者的有效率为６１.５％,ＣＯＸ-２表达阴性者有效率为８６.７％（Ｐ＜０.０５）。结论　ＣＯＸ-２有可能作为预测乳腺癌患者行紫杉醇脂质体联合表柔比星新辅助化疗疗效的分子生物学指标。     

Gemcitabine/epirubicin/paclitaxel as neoadjuvant chemotherapy in locally advanced breast cancer: a phase II trial of the NSABP Foundation Research Group

BACKGROUND: This phase II protocol of neoadjuvant chemotherapy with gemcitabine/epirubicin/paclitaxel (GET) was designed to determine the pathologic complete response (pCR) rate in the breast, clinical response rate, disease-free survival, and overall survival at 2 years as well as toxicity in patients with locally advanced breast cancer. This trial also evaluated the feasibility of tissue collection for gene-expression profiling. PATIENTS AND METHODS: Seventy-six women with stage IIB, IIIA, and IIIB breast cancer were entered into this trial. Patients received a maximum of 6 cycles of neoadjuvant GET chemotherapy every 21 days (gemcitabine 1000 mg/m2 intravenously [i.v.] on days 1 and 4, epirubicin 90 mg/m2 i.v. bolus on day 1, and paclitaxel 175 mg/m2 i.v. on day 1). After chemotherapy, patients underwent surgery and were assessed for pathologic response. RESULTS: The pCR rate among the 74 patients evaluable for efficacy was 23% (95% CI, 14%-34.2%). Adverse events among the 76 patients evaluable for toxicity included anemia requiring transfusion (14.5%), infection with grade 3/4 neutropenia (10.5%), febrile neutropenia (7.9%), and platelet transfusion (6.6%). Infectious complications occurred in 24 patients (31.6%), of whom 18.4% were in the setting of neutropenia. High-quality RNA and successful probe synthesis were obtained from all pretreatment core biopsy specimens that contained tumor cells (n=66; 88%). CONCLUSION: Neoadjuvant GET chemotherapy is an active regimen but with substantial toxicity. Tissue collection for gene-expression profiling is feasible in a multi-institutional setting.     

Influence of Neoadjuvant Therapy with Epirubicin and Docetaxel on the Expression of HER2/neu in Patients with Breast Cancer

BACKGROUND: In primary breast cancer, the expression levels of biological markers relevant to the progression of the disease may be altered by administration of anticancer drugs. Since neoadjuvant chemotherapy with epirubicin and docetaxel is increasingly used in advanced breast cancer, our purpose was to assess the influence of this neoadjuvant chemotherapy on the expression of the growth factor receptor HER2/neu. PATIENTS AND METHODS: We investigated changes of HER2/neu status by immunohistochemistry (IHC) and applied additional fluorescence in situ hybridization (FISH) in patients with potential modulation of HER2/neu status after administration of neoadjuvant chemotherapy with docetaxel and epirubicin in 97 breast cancer patients. The influence of neoadjuvant chemotherapy on HER2/neu expression was calculated by correlation of HER2/neu status before and after chemotherapy. RESULTS: The accuracy of HER2/neu assessment before and after neoadjuvant chemotherapy by IHC combined with FISH analysis in selected cases was 100%. The evaluation of HER2/neu status in these patients by IHC alone yielded accuracy of 93%. Neoadjuvant chemotherapy with epirubicin and docetaxel caused no significant modulation of HER2/neu status (p = 0.66). DISCUSSION: The administration of epirubicin and docetaxel in the neoadjuvant setting is not associated with significant changes of HER2/neu status in primary breast cancer. As a consequence, drug resistance or sensitivity is not induced by modulation of HER2/neu expression. Moreover, the time of assessment of the HER2/neu status is not a critical factor under neoadjuvant therapy with epirubicin and docetaxel.     

40例乳腺癌新辅助化疗的疗效观察

目的评价含紫杉类或葸环类药物在乳腺癌术前化疗中的疗效及副作用。方法2005年7月～2007年11月在我院治疗的40例Ⅰ～Ⅲ期原发乳腺癌患者,采用含紫杉类（TP或TE／TEC方案）或葸环类（EC／FEC方案）联合方案,术前化疗2～4个周期,33例患者接受手术,术后完成规定化疗,应用B超结合触诊判断临床疗效,观察近期疗效及毒副作用,应用x^2检验及单因素分析判定相关因素与疗效的关系。结果化疗前后中位肿瘤最大径分别为3．5厘米和2．0厘米（P=0．01）,临床有效率82．5％（33／40）,其中cCR7．5％（3／40）、cPR75％（30／40）、cSD15％（6／40）、cPD2．5％（1／40）。手术治疗33例,术后pCR9．1％（3／33）,tpCR6．1％（2／33）。这些病例中,不同肿瘤大小、受体状况、CerbB-2表达、不同分化程度以及化疗方案之间的肿瘤缓解率并无统计学差异。化疗毒副作用主要为脱发、骨髓抑制、消化道反应、口腔溃疡及外周神经毒性,心脏毒性主要表现为心律增快、心电图改变,肝功损害少见。结论紫杉类及蒽环类药物联合方案用于浸润性乳腺癌的术前化疗,可有效控制肿瘤,毒副作用可耐受。     

Clinical evaluation of effects from neoadjuvant chemotherapy with epirubicin plus paclitaxel in cases of locally advanced breast cancer--comparative study of treatment with 2 and 4 cycles

Neoadjuvant chemotherapy of epirubicin plus paclitaxel was administered to 75 patients (including a 2-cycle group of 39 patients and a 4-cycle group of 36 patients) with locally advanced breast cancer (35 cases of stage IIb, 28 of stage IIIa, 12 of stage IIIb) to compare efficacy and toxicity of 2 cycle and 4 cycle regimens. All patients were female. They were treated with epirubicin 60 mg/m2, on day 1, by i.v., followed by paclitaxel 150 mg/m2, by 3 hour continuous infusion on day 2 repeated every 3 weeks. Premedication with dexamethasone, ondansetron, diphenhydramine and cimetidine were administered to prevent gastroenteritic and allergic reactions before chemotherapy. Thirty-nine patients were given 2 cycles and thirty-six were given 4 cycles of this regimen. One of 39 patients had complete response, 28 had partial response and 10 had no change in the 2-cycle group. In addition, 21 of 36 patients had complete response (including 9 who had pathologic complete response), 13 had partial response and 2 had no change. The response rates were 74% (29/39) in the 2-cycle group and 94% (34/36) in the 4-cycle group. There were no progressive disease in these 2 groups. However a higher proportion of PR was observed in stage II patients than in stage III patients. Twelve of 36 patients underwent breast conserving surgery, as tumor size had become smaller and down-staging was realized after neoadjuvant chemotherapy. In addition, axillary lymph nodes were palpable in all 75 patients before neoadjuvant chemotherapy with the ET regimen. But 46% (18/39) in the 2-cycle group and 75% (27/36) in the 4-cycle group became impalpable. Conversely, major toxicities (including leukopenia and gastroenteric reactions) were similar in both groups, but myalgia, arthralgia, neurotoxicity and alopecia were more severe in the 4-cycle group than in the 2-cycle group. In the present study, neoadjuvant chemotherapy with a 4-cycle ET regimen was more effective than with a 2-cycle regimen in down staging locally advanced breast cancer. Although major toxicities were more severe in the 4-cycle group than in the 2-cycle group, the regimen was tolerable and safe.     

LZTS1的表达与乳腺癌化疗药物敏感性关系的研究

目的 探讨亮氨酸拉链肿瘤抑制基因1(leucine zipper tumor suppressor 1,LZTS1)与乳腺癌化疗药物敏感性的关系.方法 对122例乳腺癌手术标本行体外胶滴包埋原代细胞培养药敏检测(collagen gel droplet-embed-ded culture-drug sensitivity test,CD-DST),检测分析LZTS1表达与化疗药物敏感性的关系.免疫组织化学检测278例经新辅助化疗的乳腺癌患者活检样本中LZTS1蛋白表达情况,分析其与临床病理特征的关系.观察LZTS1表达与化疗药物敏感性及化疗反应的关系.结果 122例乳腺癌中LZTS1表达与紫杉醇及长春瑞滨的化疗药物敏感性呈正相关(r=0.311,r=0.206;均P<0.05),与其他药物(表柔比星、氟尿嘧啶及顺铂)敏感性无相关性(r=0.121,r=0.083,r=0.017;均P>0.05).Logistic回归分析显示,含紫杉醇方案(紫杉醇+多柔比星、紫杉醇+表柔比星或紫杉醇+表柔比星+环磷酰胺)化疗的乳腺癌患者的LZTS1表达情况可作为预测病理完全缓解的指标(P<0.01).结论 以紫杉醇为基础化疗方案的乳腺癌中,LZTS1可作为预测化疗反应的新指标.     

survivin—siRNA联合化疗药物对乳腺癌MCF-7细胞凋亡及逆转耐药的研究

目的观察靶向survivin的siRNA联合紫杉醇和表柔比星对乳腺癌MCF-7细胞凋亡及逆转耐药的影响。方法构建靶向survivin的siRNA表达质粒,转染乳腺癌MCF。7细胞,荧光定量聚合酶链反应（PCR）,Westernblot技术检测转染前后survivin基因表达的变化,CCK．8法检测靶向survivin的siRNA联合紫杉醇、表柔比星对MCF-7细胞药物敏感性的影响,利用流式细胞术检测细胞凋亡作用。结果survivin—siRNA-2能有效抑制survivinmRNA（0．30±0．03）和蛋白的表达（0．37±0．09）（P〈0．05）;紫杉醇[24、48h抑制率分别为（38．5±4．0）％、（41．7±6．3）％]、表柔比星[24、48h抑制率分别为（37．0±8．6）％、（40．6±12．1）％1均可抑制MCF-7细胞增殖并诱导部分细胞凋亡;当与survivin—siRNA联合时上述作用显著加强f紫杉醇24、48h抑制率分别为（76．0±2．9）％、（85．1±4．0）％;表柔比星24、48h抑制率分别为（74．6±5．6）％、（82．5±4．8）％1（P〈0．05）,并且细胞抑制率呈现时间、剂量依赖性。结论利用RNA干扰阻断survivin基因表达同时联合相应化疗药物可以显著增强MCF-7细胞对药物敏感性并促进其凋亡,该方法在乳腺癌治疗中具有潜在的临床应用价值。     

生存素乳腺癌耐药蛋白和人表皮生长因子受体2基因的表达与乳腺癌新辅助化疗疗效的关系

目的 探讨生存素(Survivin)、乳腺癌耐药蛋白(BCRP)以及人表皮生长因子受体2(HER-2)基因表达对乳腺癌TE方案新辅助化疗疗效的预测价值.方法 对56例乳腺癌患者行TE方案新辅助化疗,应用RT-PCR法检测TE方案化疗前后Survivin、BCRP和HER-2 mRNA的表达差异,并结合化疗疗效进行相关性分析.结果 56例乳腺癌患者经TE方案新辅助化疗后的总有效率为71.4％.全组完全缓解5例,病理完全缓解4例,部分缓解35例,稳定13例,进展3例.Survivin mRNA的阳性表达率由化疗前的60.7％降至化疗后的35.7％ (P =0.008);BCRP mRNA的阳性表达率由化疗前的37.5％降至化疗后的19.6％(P=0.036);HER-2 mRNA的阳性表达率由化疗前的41.1％降至化疗后的21.4％ (P =0.025).Survivin或BCRP单独阴性表达的患者化疗的有效率均较阳性表达者高(均P＜0.05).HER-2 mRNA的单独表达状况与化疗疗效无关(P =0.144).Survivin、BCRP和HER-2 mRNA均为阴性表达的患者化疗疗效高于其他各组(P =0.003).在乳腺癌组织中,Survivin、BCRP和HER-2 mRNA的表达之间不存在相关关系(P＞0.05).结论 联合检测Survivin、BCRP和HER-2的表达可作为预测乳腺癌TE方案新辅助化疗敏感性的分子生物学指标.     

紫杉醇脂质体与紫杉醇联合表阿霉素在乳腺癌新辅助化疗中的对照研究

目的　比较紫杉醇脂质体与普通紫杉醇联合表阿霉素两种方案在乳腺癌新辅助化疗中的临床疗效和安全性。方法　本试验采用开放式、随机、对照的方法进行研究。５６例需新辅助化疗的女性乳腺癌患者随机分为紫杉醇脂质体联合表阿霉素组（Ａ组）和普通紫杉醇联合表阿霉素组（Ｂ组）。Ａ组每周期予以紫杉醇脂质体１７５ｍｇ／ｍ^２,Ｂ组每周期予以紫杉醇１７５ｍｇ／ｍ^２,每周期两组表阿霉素均为７５ｍｇ／ｍ２。２１天为１周期,每周期评价毒性反应,２周期化疗后评价疗效。结果　入组病例中Ａ组完成２８例,Ｂ组完成２７例。Ａ组和Ｂ组的总有效率（ＣＲ＋ＰＲ）分别为５３.６％和４８.１％（Ｐ＞０.０５）。两组毒副反应中皮疹、皮肤潮红发生率具有明显差异,以Ａ组较低（Ｐ＜０.０５）;其他如血液学毒性、呕吐、腹泻及发热等基本一致（Ｐ＞０.０５）。结论　紫杉醇脂质体与普通紫杉醇联合表阿霉素方案在乳腺癌新辅助化疗中的疗效相当,但紫杉醇脂质体过敏反应发生率明显低于紫杉醇。     

Clinical evaluation of effects from neo-adjuvant chemotherapy with epirubicin plus paclitaxel in cases of locally advanced breast cancer

Neo-adjuvant chemotherapy of epirubicin plus paclitaxel was administered to 23 patients with locally advanced breast cancer (including 13 cases of stage IIb, 6 of stage IIIa, and 4 of stage IIIb). All patients were female. They were treated with epirubicin 60 mg/m2, on day 1, by i.v. followed paclitaxel 150 mg/m2 by 3 hours continuous infusion on day 2 and every 3 weeks repeatedly. Premedication with dexamethasone, ondansetron, diphenhydramine and cimetidine were administered to prevent gastroenteric and allergic reactions before chemotherapy. Two to 4 cycles were used. Ten out of 23 patients had a complete response, 10 had partial response, and 3 had no change. The response rate was 87% (20/23). Six out of 23 patients underwent breast conserving surgery as tumor size had become smaller and downstaging was realized after neo-adjuvant chemotherapy. The major toxicities included neutropenia, myalgia, arthralgia, nephrotoxicity, gastroenteric reactions, alopecia and flushing to the face. However, these were well tolerated in these patients.     

不同分子亚型局部晚期乳腺癌的新辅化疗反应率的临床研究(英文)

Objective: The aim of this study was to evaluate the impact of different molecular subtypes defined by immunohistochemistry (IHC) staining on the response rate for patients with locally advanced breast cancer received neoadjuvant chemotherapy. Methods: One hundred and seven breast cancer patients admitted from 2007 to 2011 who received 4 cycles of docetaxel/epirubicin-combined (TE) neoadjuvant chemotherapy were retrospectively reviewed, the patients were classified into 4 subtypes: luminal A, luminal B, HER-2 and triple negative breast cancer (TNBC) according to different combination patterns of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor-2 (HER-2) expression defined by IHC method. The correlation between response rate and the molecular subtypes were analyzed. Results: The pathological complete response (PCR), clinical complete response (CCR), clinical partial response (CPR), and clinical stable disease (CSD) rate of whole group was 15.89% (17/107), 22.43% (24/107), 63.55% (68/107), 14.02% (15/107), respectively, and the overall response rate (ORR) was 85.98% (92/107). The PCR rate and ORR of luminal A, luminal B, HER-2 and TNBC subtypes was 4.76% and 73.81%; 16.67% and 83.33%;17.65% and 100.00%; 30.00% and 96.67%, respectively. The PCR and ORR rate of HER-2/TNBC subtypes was higher than that of luminal A/B subtypes (P = 0.019, P = 0.002, respectively). Conclusion: Different molecular subtypes display different response rate for patients with locally advanced breast cancer received neoadjuvant TE chemotherapy, HER-2/TNBC subtypes have a higher PCR and ORR rate than that of luminal A/B subtypes.     

TE方案与TEC方案在乳腺癌新辅助化疗中的疗效比较

[目的]对比分析多西他赛联合表柔比星加/不加环磷酰胺（TEC/TE）两种新辅助化疗方案治疗乳腺癌的近期疗效。[方法]回顾性分析2006~2009年收治的Ⅱ~Ⅲ期乳腺癌新辅助化疗患者108例的临床病理资料,分别术前接受新辅助化疗的TE方案（n=62）及TEC方案（n=46）,两组患者均在术前接受2~4个周期化疗。TE方案：多西他赛75mg/m2,第1天静脉滴注;表柔比星（EPI）60mg/m2,第1天静脉滴注。[结果]全组108例患者均可评价疗效,CR 10例（9.25%）,PR 75例（69.44%）。TE组有效率为75.81%,而TEC组有效率为82.61%,两组有效率无统计学差异（χ2=0.729,P=0.392）。Ⅱ期患者28例均生存。Ⅲ期患者80例3年生存率为82.4%,其中TE组44例3年生存率为74.6%;而TEC组36例3年生存率为91.8%,差异有统计学意义（χ2=4.149,P=0.042）。[结论]在Ⅱ~Ⅲ期乳腺癌患者新辅助化疗中,TE与TEC方案近期疗效相似,TEC组3年生存率较佳,有待于进一步加大样本量进行研究。     

Her-2/neu expression in locally advanced breast carcinomas: pre- and post-neoadjuvant chemotherapy

Clinical studies have shown a correlation of HER-2/neu amplification/over-expression and favorable response to neoadjuvant chemotherapy and anti-HER-2/neu antibody treatment. However, contradictory findings also have been reported. Some tumors may develop resistance to neoadjuvant chemotherapy after an initial period of sensitivity. Our study attempts to evaluate the effects of neoadjuvant chemotherapy on HER-2/neu status in locally advanced breast cancer. Thirty-nine patients with locally advanced breast cancers established by core needle biopsy received neoadjuvant chemotherapy and were compared with 60 patients with breast cancers who did not receive neoadjuvant chemotherapy. IHC for HER-2/neu was performed on paraffin sections of the core biopsy before treatment and the excised specimen following chemotherapy and scored as Negative (0-1+), 2+ and 3+. The results of the study and the controls were compared and analyzed using Fisher's exact test. HER-2/neu IHC scores decreased in 28.5% (15/39) of patients receiving neo-adjuvant chemotherapy compared to 11.7% (7/60) of patients in the control (p < 0.013). HER-2/neu IHC status changed from strongly positive to negative (3+ to 0) in five of 39 (12.5%) in the study group and in 2 of 60 (3.3%) in control group (p = 0.104). For patients receiving neoadjuvant chemotherapy in whom the tumor becomes refractory to chemotherapy or recurs, repeat testing for HER-2/neu status may be necessary. Elimination of HER-2/neu positive tumor cells may account for the changes in the IHC scores and the development of resistance to neoadjuvant chemotherapy.     

A prospective randomized pilot study to evaluate predictors of response in serial core biopsies to single agent neoadjuvant doxorubicin or paclitaxel for patients with locally advanced breast cancer.

INTRODUCTION: Response to neoadjuvant chemotherapy for locally advanced breast cancer can be correlated with long-term outcomes. Surrogate end-point biomarkers may be used to assess response to the treatment. Most reported studies assessed the effects of combination chemotherapy. We assessed the feasibility of obtaining serial core breast biopsies, and correlated rates of apoptosis, proliferation, and expression of related proteins at baseline, during, and after neoadjuvant single agent chemotherapy for locally advanced breast cancer with response. EXPERIMENTAL DESIGN: Women with a histologically confirmed unresected T(3) or T(4) infiltrating carcinoma of the breast were eligible. The first 20 patients received three cycles of doxorubicin 90 mg/m(2) followed by three cycles of paclitaxel 250 mg/m(2), or the reverse. Nine women received four cycles of each (doxorubicin 60 mg/m(2) and paclitaxel 175 mg/m(2)). Cycles were administered 14 days apart with filgastrim. End points included: (a). clinical and pathological response; (b). serial apoptotic [terminal deoxynucleotidyl transferase (Tdt)-mediated nick end labeling] and proliferation (immunohistochemistry, IHC) rates; and (c). expression (IHC) of estrogen receptor, HER2, bcl2, and p53. RESULTS: From April 1997 to June 2001, 29 women were randomized. Twelve patients (42%) had a clinical complete response (cCR), and 16 (55%) had a clinical partial response. Five women (17%) had a pathological complete response, 7 (24%) had microscopic residual disease, and 17 (58%) had macroscopic residual disease. Higher baseline apoptosis and proliferation were associated with an improved pathological response (P = 0.006 and 0.003, respectively). Among 14 evaluable patients, apoptosis increased in women who had a cCR to the first agent but not in women without a cCR. Estrogen receptor-positive patients had a worse pathological response (P = 0.004). CONCLUSIONS: The selected regimen is efficacious. It is feasible to obtain serial core biopsies that are informative for studies of apoptosis and IHC. This clinical design can serve as a model for combining standard chemotherapy and novel agents.     

Neoadjuvant gemcitabine therapy for breast cancer

Neoadjuvant chemotherapy has become a standard treatment in the management of locally advanced breast cancer. Patients with earlier-stage disease may also benefit from neoadjuvant treatment in terms of improved rates of breast-conserving surgery and thus better quality of life. Gemcitabine is a pyrimidine analogue that has shown activity in a variety of solid tumors, a good toxicity profile, and nonoverlapping toxicity with other chemotherapeutic agents. Several phase II/III studies are assessing gemcitabine combined with anthracyclines, taxanes, and/or vinorelbine both in the neoadjuvant and metastatic disease settings. This article reviews developments in neoadjuvant use of gemcitabine in combination with anthracyclines and taxanes. Several phase II trials of gemcitabine combined with doxorubicin/epirubicin or with doxorubicin/paclitaxel have been carried out. Preliminary findings demonstrate increased complete response rates and good tolerability of these regimens in patients with breast cancer.     

ER,PgR, HER-2, Ki-67, topoisomerase IIα, and nm23-H1 proteins expression as predictors of pathological complete response to neoadjuvant chemotherapy for locally advanced breast cancer

The purpose of this study was to evaluate the importance of biological markers to predict pathologic complete response (pCR) to neoadjuvant chemotherapy (NCT) in patients with locally advanced breast cancer (LABC) One hundred and twelve consecutive patients with clinical stage III LABC who had received NCT with docetaxel and epirubicin from March 2006 to March 2009 were included in this retrospective study. The pre-NCT treatment expression levels of Ki-67 proliferation index, estrogen receptor (ER), progesterone receptor (PgR), epidermal growth factor receptor 2 (HER-2), Topoisomerase II alpha (Topo-II), and nm23-H1 were detected by immunohistochemistry (IHC). A total of 361 cycles were administered with the median number of three cycles per patient (range, 2–6). The pCR rate was 9.8% (95% CI, 4.3–15.3%). In univariate analysis, poor tumor differentiation, both negative of ER/PgR, negative Topo-II, and positive nm23-H1 were found to be significantly predictive of a pCR. ER/PgR status and nm23-H1 were significant for pCR on multivariate analysis (P = 0.006 and 0.025, respectively). ER/PgR status and nm23-H1 are independent predictive factors of pCR to neoadjuvant docetaxel plus epirubicin combination chemotherapy in patients with LABC.     

Gemcitabine/anthracycline combinations in metastatic breast cancer

Gemcitabine has demonstrated single-agent efficacy in the treatment of advanced breast cancer, with response rates of up to 42%. The agent is well tolerated, with relatively mild side effects, and has limited overlapping toxicities with other drugs used in combination chemotherapy for breast cancer. It is, therefore, a good candidate for inclusion in multidrug regimens for the treatment of this disease. This article reviews results of gemcitabine/anthracycline-containing double- and triple-drug combinations used to treat patients with early-stage and advanced breast cancer. Results from phase I and II trials were promising, with good tolerability and overall response rates ranging from 33%-89% in advanced disease and up to 95% in the neoadjuvant treatment of early-stage disease. A phase III trial is currently comparing gemcitabine/epirubicin/paclitaxel and 5-fluorouracil/epirubicin/cyclophosphamide in patients with advanced breast cancer. Preliminary toxicity data on 78 patients show that both regimens were well tolerated, with similar incidences of treatment-related effects. Additional comparative studies of gemcitabine-containing drug regimens in breast cancer are warranted.     

A multicentre phase II pilot study of epirubicin and Taxol (paclitaxel) in patients with advanced breast cancer

Anthracyclines are the gold standard monotherapy for metastatic breast cancer. Higher response rates are seen with drug combinations, especially with newer agents such as taxanes. The purpose of this study was to evaluate the toxicity and activity of the combination of paclitaxel and epirubicin in patients with advanced breast cancer. Thirty-five women with locally advanced or metastatic breast cancer (first and second relapse) were treated with epirubicin 75 mg/m2 and paclitaxel 200 mg/m2 3-weekly. Six centres recruited 35 patients; 34 (97%) were assessable for response. Eighteen had undergone prior chemotherapy, including six (17%) with anthracycline-containing regimens. Grade 4 neutropenia was found in 33 patients (94%), which was of 4 days' average duration; however, infective complications were rare, with only nine cycles (6%) complicated by neutropenic sepsis. There were two sepsis-related deaths. Symptomatic cardiotoxicity was infrequent, although a >15% decline in cardiac function was recorded in five patients (14%). Grade 3 peripheral neuropathy occurred in three patients (9%). The overall response rate was 50% (95% confidence interval 33-67) (complete response 12%; partial response 38%), with a median duration of response of 31 weeks. The median time to progression was 27 weeks, with a median survival of 48 weeks. This regimen appears to be a relatively safe, tolerable and effective treatment for advanced breast cancer. A United Kingdom Co-ordinating Committee for Cancer Research Phase III trial (AB-01) comparing this combination of epirubicin and paclitaxel with cyclophosphamide and paclitaxel completed accrual in November 1999.