乳腺癌TAC新辅助化疗与相关不良预后因素的关系分析

目的 探讨乳腺癌紫杉醇+环磷酰胺+吡柔比星（TAC）方案新辅助化疗与相关不良预后因素的关系。方法 分析1561例乳腺癌患者（TAC新辅助化疗180例）同侧淋巴结转移、锁骨上淋巴结转移、残余脉管内肿瘤和肿瘤结节的发生情况。结果 接受TAC新辅助化疗的乳腺癌患者同侧淋巴结转移率、锁骨上淋巴结转移率、残余脉管内肿瘤发生率和肿瘤结节发生率均高于直接手术患者（P﹤0.01）。轻度缓解和部分缓解患者同侧腋窝淋巴结转移率和残余脉管内肿瘤发生率均高于病理学完全缓解（pCR）患者,差异均有统计学意义（P﹤0.01）。结论TAC新辅助化疗可能提高乳腺癌同侧淋巴结转移率、锁骨上淋巴结转移率、残余脉管内肿瘤发生率和肿瘤结节发生率,尤其新辅助化疗效果不佳的患者,可能增加潜在复发与转移风险。     

80例乳腺癌患者新辅助化疗预后影响因素分析

目的探讨乳腺癌患者新辅助化疗预后影响因素。方法回顾性分析2010年4月至2014年4月在昆山市第二人民医院乳腺外科住院进行新辅助化疗治疗的80例乳腺癌患者的临床病理资料。结果单因素分析显示,不同年龄、TNM分期、雌激素受体(ER)表达、孕激素受体(PR)表达、人表皮生长因子受体2(HER-2)表达、淋巴结转移枚数、新辅助化疗(NAC)方案、疗效评价,新辅助化疗乳腺癌患者的无病生存率均有统计学意义(均P<0.05),不同年龄、TNM分期、ER表达、PR表达、HER-2表达、淋巴结转移枚数、疗效评价,新辅助化疗乳腺癌患者的总生存率均有统计学意义(均P<0.05),未发现不同NAC治疗周期、手术方式、术后有无放疗对新辅助化疗乳腺癌患者的无病生存率和总生存率有统计学意义(均P>0.05)。多因素分析显示,TNM分期、ER表达、HER-2表达、疗效评价均为新辅助化疗乳腺癌患者无病生存时间及总生存时间的独立预后因素,差异均有统计学意义(均P<0.05)。结论 TNM分期、ER表达、HER-2表达、疗效评价为新辅助化疗乳腺癌患者预后的影响因素。     

影响年轻乳腺癌患者新辅助化疗后病理完全缓解与预后的因素分析

目的 探讨影响年轻乳腺癌患者新辅助化疗后病理完全缓解(pCR)与预后的因素。方法 回顾性分析行新辅助化疗的145例年轻乳腺癌患者临床资料,分析影响年轻乳腺癌患者新辅助化疗后pCR与预后的因素。结果 145例年轻乳腺癌患者新辅助化疗后pCR率为34.48%。ER阳性、PR阳性、临床N分期、Ki67阳性、化疗方案与pCR有关(P<0.05),HER-2、化疗周期、分子分型、临床T分期与pCR无关(P>0.05);多因素分析显示,Ki67阳性、临床N分期是影响年轻乳腺癌患者新辅助化疗后pCR的独立因素(P<0.05且OR>1)。145例年轻乳腺癌患者新辅助化疗后1年复发率37.93%。ER阳性、PR阳性、临床T分期、临床N分期、pCR与新辅助化疗后预后有关(P<0.05),HER-2、Ki67、化疗方案、化疗周期、分子分型与新辅助化疗后预后无关(P>0.05);多因素分析显示,临床T分期、pCR是影响年轻乳腺癌患者新辅助化疗后预后的独立因素(P<0.05且OR>1)。结论 Ki67阳性、临床N分期是影响年轻乳腺癌患者新辅助化疗后pCR的独立因素...     

乳腺癌的新辅助化疗

新辅助化疗是指对非转移性肿瘤在应用局部治疗前进行的全身性的、系统性的细胞毒性药物治疗,目前已成为乳腺癌治疗标准中的重要组成部分。由于各种文献报道中对新辅助化疗的描述的角度不同,这种肿瘤治疗的方式又曾分别被称为术前化疗、首次化疗和诱导化疗。在乳腺癌中,其主要目的在于:①对不适用手术的局部晚期乳腺癌患者降低分期,使手术成为可能;②对部分可手术的早期乳腺癌患者提高保乳手术的可能性和成功率;③获得早期的肿瘤生物学特性及对化疗药物的敏感性资料。     

影响青年乳腺癌患者新辅助化疗后病理完全缓解和预后的病理因素分析

目的:探讨影响青年乳腺癌患者新辅助化疗（neoadjuvant chemotherapy,NAC）后病理完全缓解（pathological complete response,pCR）和预后的临床病理因素。方法:回顾性分析2010年01月至2018年12月我院甲乳外科收治年龄≤35岁行NAC的女性乳腺癌患者的临床病理资料。NAC后依据Miller-Payne评分系统,将患者分为pCR组和非pCR组。探讨临床病理因素对青年乳腺癌患者pCR、复发转移和死亡的影响,同时分析pCR与无病生存期（disease free survival,DFS）与总生存期（overall survival,OS）之间的相关性。结果:168例患者中pCR 37例,pCR率为22.0%。体质量指数(body mass index,BMI)、术前淋巴结状态、雌激素受体（estrogen receptor,ER）、孕激素受体（progesterone receptor,PR）、人类表皮生长因子受体2（human epidermal growth factor receptor-2,HER-2）、Ki-67、p53及分子分型与青年乳腺癌患者NAC后的pCR率关系密切（P＜0.05）。肿瘤大小、术前淋巴结状态、ER、PR、HER-2、p53及分子分型影响患者的复发转移和死亡（P＜0.05）,同时肿瘤大小、术前淋巴结状态、组织学分级、ER、PR、HER-2、Ki-67及分子分型均是DFS和OS的独立影响因素（P＜0.05）。66例复发转移患者中pCR患者7例,占pCR患者的18.9%（7/37）,pCR组和非pCR组DFS比较差异具有统计学意义（P＜0.05）。38例死亡患者中pCR患者3例,占pCR患者的8.1%（3/37）,pCR组和非pCR组OS比较差异具有统计学意义（P＜0.05）。结论:影响青年乳腺癌患者pCR和预后的临床病理因素较多,获得pCR的患者具有更好的远期预后。     

乳腺癌新辅助化疗患者病理完全缓解的影响因素及生存分析*

目的：探讨乳腺癌新辅助化疗患者病理完全缓解的影响因素及病理完全缓解对预后的影响。方法：选择河南省肿瘤医院乳腺科2008年1 月至2014年12月女性乳腺癌新辅助化疗患者267 例作为研究对象,收集患者的临床和病理资料,随访患者的生存情况。结果：单因素分析显示新辅助化疗病理完全缓解患者的体质量、哺乳时间、化疗周期、肿瘤直径和未病理完全缓解患者比较,差异均具有统计学意义（P < 0.05）;病理完全缓解患者ER、PR、HER-2 和分子分型与未病理完全缓解比较,差异均有统计学意义（P < 0.05）。 多因素分析发现体质量和ER是乳腺癌患者新辅助化疗病理完全缓解的独立预测因素（P < 0.05）。 生存分析病理完全缓解患者和未病理完全缓解患者的无病生存期和总生存期比较,差异无统计学意义（P > 0.05）。 结论：乳腺癌患者体质量和ER是新辅助化疗病理完全缓解的独立预测因素,新辅助化疗病理完全缓解对患者生存无显著影响。     

乳腺癌新辅助化疗残余肿瘤组织病理信息与预后分析

目的探讨乳腺癌新辅助化疗前后肿瘤组织病理信息的变化及对预后的影响。方法对2014年1月—2016年5月就诊于辽宁省肿瘤医院乳腺外科并行规范乳腺癌新辅助化疗的177例患者回顾性分析,探讨乳腺癌新辅助化疗前后肿瘤组织病理信息的变化,并分析残余肿瘤组织病理信息对无病生存期(DFS)和总生存期(OS)的影响。结果 177例乳腺癌患者中位随访时间为37个月,37个月无病生存率和总生存率分别为84.0%和95.0%,4年无病生存率和总生存率分别为79.7%和81.1%。新辅助化疗后乳腺癌患者的DFS独立危险因素为原始T分期、原始N分期、存在脉管侵袭、新辅助化疗后Ki-67增加。OS的独立危险因素为原始T分期、原始N分期。而新辅助化疗前后ER状态的改变、PR状态的改变、HER-2状态的改变与患者预后无关(P>0.05)。结论乳腺癌新辅助化疗前后分子生物学指标ER、PR、HER-2、Ki-67可以发生改变,但与乳腺癌患者预后无关。原始肿瘤T分期、原始肿瘤N分期、存在脉管侵袭和Ki-67增加是影响乳腺癌患者DFS的危险因素。原始肿瘤T分期、原始肿瘤N分期是影响乳腺癌患者OS的危险因素。     

Ⅲ期乳腺癌的新辅助化疗

报告Ⅲ期乳腺癌经新辅助化疗后的治疗结果。从１９８４年１月～１９８９年１月，应用新辅助化疗的方法治疗Ⅲ期乳腺癌３０例．其５年生存率为７３．４％，非新辅助化疗的Ⅲ期乳腺癌患者的５年存活率为４０．０％。临床观察发现术前化疗后原发肿瘤明显变小。光镜下见肿瘤组织明显坏死，炎细胞浸润，肿瘤区域内见血管内皮增生、管壁增厚、透明变性和管腔闭塞．癌巢间胶原纤维增生及纤维化改变。提示：应用新辅助化疗治疗Ⅲ期乳腺癌能够改善病人的预后。     

乳腺癌新辅助化疗的研究进展

乳腺癌是一种在肿瘤生物学及临床征象上呈多样性的全身性疾病。新辅助化疗(neoadjuvant chemotherapy,NCT)作为乳腺癌综合治疗的一部分,在局部晚期乳腺癌中的地位已经确立,在可手术乳腺癌治疗中的作用也越来越重要。它可使乳腺癌原发肿瘤及淋巴结转移灶明显缩小,提高进展期乳腺癌的手术切除率,增加乳腺癌保留乳房的机会,获得了至少等同术后辅助化疗一样的疗效,同时可获得体内的药敏试验,其临床疗效可能成为预测治疗结果,指导综合治疗方案制定以及判断预后的重要标志。     

Neo-Bioscore评分在乳腺癌新辅助化疗预后评估中的价值

摘 要：［目的］ 探讨Neo-Bioscore评分系统对比临床分期系统、病理分期系统以及CPS+EG评分系统在乳腺癌新辅助化疗预后评估的价值。［方法］ 收集2010年1月至2017年6月乳腺癌新辅助化疗198例患者资料,随访时间为期5年,分别通过4个不同的分期系统进行预后评估,计算5年总体生存率。 ［结果］ 全组198例患者5年总生存率为72%;不同病理分期之间生存情况存在较多的交叉(P>0.05),而Neo-Bioscore评分系统变化区间最大（P<0.05）。Neo-Bioscore高分值（>3分）与低分值组（≤3分）组生存率比较差异有统计学意义（χ2=17.353,P<0.05）。［结论］ Neo-Bioscore分期系统显示出较好的预后评估价值,能更全面地预测乳腺癌新辅助化疗患者的预后。     

可手术乳腺癌的新辅助化疗

新辅助化疗已被广泛用于局部晚期乳腺癌,早期可手术乳腺癌的新辅助化疗应用价值还在探讨之中。本文综述了新辅助化疗治疗可手术乳腺癌基础及临床方面的最新进展,认为新辅助化疗应用于早期可手术乳腺癌,可明显消退肿瘤,提高乳房保留治疗率,可获得至少与辅助化疗同样的总生存率。     

Prognostic significance of a complete pathological response after induction chemotherapy in operable breast cancer

Only a few papers have been published concerning the incidence and outcome of patients with a pathological complete response after cytotoxic treatment in breast cancer. The purpose of this retrospective study was to assess the outcome of patients found to have a pathological complete response in both the breast and axillary lymph nodes after neoadjuvant chemotherapy for operable breast cancer. Our goal was also to determine whether the residual pathological size of the tumour in breast could be correlated with pathological node status. Between 1982 and 2000, 451 consecutive patients were registered into five prospective phase II trials. After six cycles, 396 patients underwent surgery with axillary dissection for 277 patients (69.9%). Pathological response was evaluated according to the Chevallier's classification. At a median follow-up of 8 years, survival was analysed as a function of pathological response. A pathological complete response rate was obtained in 60 patients (15.2%) after induction chemotherapy. Breast tumour persistence was significantly related to positive axillary nodes (P=5.10(-6)). At 15 years, overall survival and disease-free survival rates were significantly higher in the group who had a pathological complete response than in the group who had less than a pathological complete response (P=0.047 and P=0.024, respectively). In the absence of pathological complete response and furthermore when there is a notable remaining pathological disease, axillary dissection is still important to determine a major prognostic factor and subsequently, a second non cross resistant adjuvant regimen or high dose chemotherapy could lead to a survival benefit.     

Prognostic value of residual node involvement in operable breast cancer after induction chemotherapy

The purpose of this retrospective study was to evaluate the influence of axillary disease on patients' survival after neoadjuvant chemotherapy and to assess patient and tumor characteristics associated with post-chemotherapy axillary involvement.After six induction cycles, 277 patients with operable breast cancer (stage II–III) underwent surgery with axillary dissection, followed by radiotherapy (n = 267) or additional chemotherapy (n = 63) and adjuvant tamoxifen therapy (n = 138). At a median follow-up of 8.5 years, overall survival (OS) and disease-free survival (DFS) were analyzed as a function of node involvement.The differences in OS and DFS according to the number of positive nodes were highly statistically significant with a decreased survival associated with the increasing number of nodes (p = 5 × 10^–6 and 9 × 10^–7, respectively). Upon multivariate analysis, the node number after chemotherapy appeared as the most significant prognostic factor (p = 7 × 10^–4 for OS and p = 3 × 10^–5 for DFS). All the other classical prognostic factors were insignificant, except post-chemotherapy Scarff–Bloom–Richardson (SBR) grading for OS (p = 8 × 10^–4) and adjuvant hormonotherapy for DFS (p = 1 × 10^–2).Although constituting a different parameter from primary surgery data, the number of positive nodes after chemotherapy could still remain a valuable prognostic factor at secondary surgery, raising the question for high risk patients of a second non-cross-resistant adjuvant regimen, or high dose chemotherapy with peripheral blood stem cells support.     

Short-term Intensive Neoadjuvant Chemotherapy Improving 10-year Survival for Patients with Stage Ⅱ and Operable Stage Ⅲ Breast Cancer

Objective To evaluate the 10-year curative effects of short-term intensive neoadjuvant chemotherapy for operable breast cancer. Methods A total of 510 patients with stagell and operable stagelll breast cancer were divided into group A (preoperative neoadjuvant chemotherapy 251 cases) and group B (postoperative adjuvant chemotherapy 259 cases). The patients in group A received short -term and intensive neoadjuvant chemotherapy for 4 weeks followed by modified radical mastectomy two weeks after the chemotherapy. The postoperative adjuvant chemotherapy began within two weeks after surgery. The same chemotherapeutic regimen was used for both groups. Results For stage III in group A the 5-year overall survival rate (OS) and disease-free survival rate (DFS) were 59.2% and 54.9% respectively which were higher than those in group B (28.3% and 20.8% respectively,P<0.05). The 10-year OS and DFS were 78.1% and 73.5% respectively for stage II in group A which were higher than those in group B (68.4% and 60.7%,P< 0.05). The 10-year OS and DFS were 42.3% and 40.4% respectively for stage III in group A which were higher than those in group B (20.4% and 18.4% respectively,P<0.05). Conclusion The results showed that intensive neoadjuvant chemotherapy can improve the 10-year survival for patients with stage II and operable stage III breast cancer.     

High prognostic significance of residual disease after neoadjuvant chemotherapy: a retrospective study in 710 patients with operable breast cancer

Summary Prognostic factors are used to help clinical decision-making in selecting the appropriate treatment for individual patients. The purpose of this retrospective study was to identify one or more factors associated with overall survival (OS) and disease-free survival (DFS), in 710 patients with operable breast cancer, subjected to neoadjuvant chemotherapy followed by surgery, radiotherapy and adjuvant treatments. At a median follow-up of 7.6 years, univariate analysis showed that pathological complete response (pCR) was significantly related to survival (p < 0.003), as well as accepted prognostic factors, as SBR and MSBR grades, hormonal receptors or node involvement at surgery, who remained significant in our study (p < 0.001). The revised Nottingham prognostic index (NPI) and related indices (BGI, MNPI and MBGI) were also significantly associated to survival (p < 0.003). In multivariate analysis, node involvement and MSBR grade remained prognostic factors for OS and DFS (p < 0.0003 and p < 0.02, respectively). The MNPI and pCR were significantly related with OS (p = 0.04) and pts with hormonal receptor-positive tumours had a better DFS than others (p = 0.004). Among all clinical and pathological parameters, axillary dissection after neoadjuvant chemotherapy is still important to determine node involvement, a major prognostic factor. Moreover, MSBR grade seemed to be more accurate and predictive of long-term outcome than the standard SBR grade. It is concluded that, outside any other ‘biological’ factor, residual disease in breast and nodes must be strongly considered after an induction chemotherapy so as to choose adjuvant treatment for the individual patient. Address for offprints and correspondence: Sophie Amat, Centre Jean Perrin, Bureau de Recherche Clinique, 58 rue Montalembert, BP 392, 63011 Clermont-Ferrand Cedex 1, France; Tel.: +33-4-73-27-80-05; Fax: +33-4-73-27-80-29; E-mail: sophie.amat@libertysurf.fr An erratum to this article can be found at     

Prognostic value of persistent node involvement after neoadjuvant chemotherapy in patients with operable breast cancer

Neoadjuvant chemotherapy is able to reduce the size of the majority of breast tumours and down-stage axillary-node status. The aim of this study was to assess the prognostic value of persistent node involvement after neoadjuvant chemotherapy. A total of 488 patients with T2-T3, N0-N1 breast cancer treated by neoadjuvant chemotherapy followed by tumour excision and axillary lymph-node dissection between 1981 and 1992 were selected from the Institut Curie database. Median follow-up was 7 years. Overall objective response rate before local treatment was 52% and breast tumour size was reduced in 83% of patients. No pathologic nodal involvement was observed in 46. 5% of patients. Patients with > or = eight positive nodes had a very poor median disease-free survival of only 20 months. Their 10-year disease-free survival rate was 7%, while the 10-year disease-free survival rate for patients with no node involvement was 64%. Median survival for patients with > or = eight nodes positive was 48 months and the 10-year survival rate was 26% (P < 0.0001). On multivariate analysis, outcome was strongly correlated with pathological nodal status, tumour grade, hormonal receptor status and clinical response of the tumour. In conclusion, patients with extensive nodal involvement after neoadjuvant chemotherapy have a very poor outcome. Second-line treatment should be considered in this population.     

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。     

Time-varying effect and long-term survival analysis in breast cancer patients treated with neoadjuvant chemotherapy

Background:

Recent studies have indicated the prognostic value of tumour subtype and pathological complete response (pCR) after neoadjuvant chemotherapy (NAC). However these results were reported after a short follow-up and using a standard Cox model which could be unsatisfactory for time-dependent factors. In the present study, we identified the prognostic factors for long-term outcome after NAC, considering that they could have an inconstant impact over time.

Methods:

Prognostic factors from 956 consecutive breast cancer patients treated with NAC were identified and associated with long-term outcomes. We estimated survival by a time function multivariate Cox model regression and stratified by follow-up length.

Results:

The prognostic value of tumour histological grade and hormone receptors status varied as distant recurrence-free interval (DRFI) increased. The multivariate analysis identified the following significant prognostic factors: tumour size, N stage, clinical and pathological response to NAC, hormone receptors (HR) status and histological tumour grade. The ‘prognostic benefit'' of low-grade and positive-HR status decreased over the years. Thus, in the early years after cancer diagnosis, the hazard ratio of distant recurrences in patients with positive-HR status increased from 0.26 (95% CI 0.1–0.4) at 6 months to 2.2 (95% CI 1.3–3.7) at 120 months. The histological tumour grade followed a similar trend. The hazard ratio of grade III patients compared with grade I was 1.83 (95% CI 1.1–2.8) at 36 months and diminished over time to 0.70 (95% CI 0.4–1.3) at 120 months. This indicates that the risk of recurrence for positive-HR patients was 74% lower at 6 months compared with the negative-hormone receptor group, but 30% higher at 5 years and more than double at 10 years. High-grade tumours presented a risk of 83% in the earlier years decreasing to 30% at 10 years versus the low-grade group.

Conclusion:

From the present study, we conclude the importance of identifying time-dependent prognostic factors. Distant recurrence-free interval within women who receive NAC are influenced by achieving pCR and breast cancer subtype. Tumours with more aggressive biology have poorer survival during the first 5 years, but if they exceed this point their prognostic impact is no longer significant. Conversely, positive-HR patients remain at risk for distant recurrence for many years.     

Phase II trial combining docetaxel and doxorubicin as neoadjuvant chemotherapy in patients with operable breast cancer.

BACKGROUND: This study was conducted to assess the antitumour activity of docetaxel in combination with doxorubicin for neoadjuvant therapy of patients with breast cancer. PATIENTS AND METHODS: Forty-eight women were treated with intravenous doxorubicin 50 mg/m(2) over 15 min followed by a 1-h infusion of docetaxel 75 mg/m(2) every 3 weeks for six cycles. Dexamethasone or prednisolone premedication was allowed. Granulocyte colony-stimulating factor was not allowed as primary prophylaxis. The primary end point was the pathologically documented complete response rate (pathological response). RESULTS: The mean relative dose intensity calculated for four or more cycles was 0.99 for doxorubicin and 0.99 for docetaxel. Overall, the pathological response rate was 13%. There were 11 complete and 29 partial clinical responses for an overall response rate of 85% [95% confidence interval (CI) 75% to 95%] in the evaluable population (n = 47). Disease-free and overall survival rates were 85% (95% CI 71% to 94%) and 96% (95% CI 85% to 99%), respectively, after a median follow-up of 36.6 months. Grade 3/4 neutropenia was observed in 65% of patients and 17% reported grade 4 febrile neutropenia. CONCLUSIONS: Docetaxel and doxorubicin is an effective and well-tolerated combination in the neoadjuvant therapy of breast cancer. Future controlled trials are warranted to investigate the best schedules and to correlate response with biological factors.