新辅助化疗对晚期乳腺癌的作用

晚期乳腺癌的治疗在临床上是较为棘手的，尤其是肿瘤巨大、广泛侵犯皮肤和胸壁的情况出现时，难以施行外科手术。近十年来新辅助化疗在临床上的应用越来越广泛，其对晚期乳癌的治疗作用也得到肯定。但对采用何种化疗方案和剂量目前尚无统一的意见。我们近三年来对晚期乳腺癌患者开展了新辅助化疗，现报告如下。     

局部晚期乳癌新辅助化疗疗效分析

目的:评价术前辅助化疗在晚期乳癌治疗中的价值。方法:对15例局部晚期乳癌进行了术前三个疗程CEF方案化疗,对其结果进行分析。结果:完全缓解占多数,部分缓解者少部分,部分无效。结论:证明术前化疗对部分局部晚期乳癌有使病灶缩小、降低TNM分期作用,减少微小转移灶,有利于指导术后化疗方案选择,对术后综合治疗及五年生存率有积极影响。     

乳腺癌的新辅助化疗

随着临床和基础研究的不断深入,乳腺癌新辅助化疗逐渐成为乳腺癌临床研究中十分活跃的领域.理论上,新辅助化疗较辅助化疗有诸多优势,但多个大型临床试验结果表明,新辅助化疗并不能显著改善患者生存.许多因素可能与之有关,例如,以往的研究在最初设计时多仅根据患者临床分期来决定患者是否需要新辅助化疗,而忽视了重要生物学指标雌激素受体(ER)、Her-2等对疗效的影响,且不同研究中生物学指标的检测方法及使用的化疗方案也不一致.本文结合最近的文献资料,就生物学指标对乳腺癌新辅助化疗的影响及其他几个临床上十分关注的问题谈一些个人的体会和看法,与同行探讨.     

乳腺癌的新辅助化疗

本文回顾了有关乳腺癌新辅助化疗的临床研究，认为可使大部分原发性乳腺癌体积明显缩小，进而使80％的可手术治疗的患者能选择保留乳房术式。虽然理论上可更大程度地杀灭亚临床的微小转移灶，减少耐药细胞株的产生，但在提高这部分患者的无复发生存率及总体生存率方面尚无临床定论。     

诺维本加阿霉素在局部晚期乳腺癌新辅助化疗中的应用

目的：了解诺维本加阿霉素的新辅助化疗方案在局部晚期乳腺癌综合治疗中的作用。方法：３１例Ⅱｂ至Ⅲｂ期的乳腺癌病人,术前均经病理或细胞学检查证实。中位年龄４８岁,化疗用药为ＮＶＢ ４０ｍｇ ｄ１,８＋ＡＤＭ ４０ｍｇ ｄｌ,每３周为一疗程,术前用药２疗程,评估新辅助化疗后肿瘤的缓解情况和随访长期生存率。结果：本组总体化疗有效率为６７．７％,肿瘤原发灶完全缓解（ＣＲ）１例,部分缓解（ＰＲ）２０例,无变化（ＳＤ）１０例;腋淋巴结临床ＣＲ１２例,ＰＲ１４例,ＳＤ５例。术后中位随访期３６个月,术后死亡６例,复发９例,健在１６例。结论：诺维本加阿霉素的联合术前化疗能使局部晚期乳腺癌的原发灶和腋淋巴结缩小,肿瘤降期,亦能减少肿瘤复发和远处转移,且不良反应较轻。     

局部晚期乳腺癌分子亚型与新辅助化疗疗效关系的研究

Objective To explore the relationship between the four different molecular subtypes of locally advanced breast cancer(LABC) and the clinical effect of neoadjuvant chemotherapy containing docetaxel and anthracyclines on breast cancer. Methods The record of 68 patients with LABC who were treated with the therapeutic scheme was reviewed. Breast cancer molecules were diagnosed by core needle biopsy through IHC and were divided into four subtypes. After 3 to 5 courses of treatment, the relationship of molecular subtype and clinical effects was analyzed. Results Univariate analysis showed that absence of estrogen receptor (ER) expression and size of tumor (≤5cm) were predictive factors for clinical complete response (cCR) (P<0.05).Over expression of HER-2 and molecular subtypes were predictive for pathologic complete response (pCR) (P<0.05). pCR rate of HER2+/ER- subtype in this therapeutic scheme was, higher than that of other subtypes and pCR rate of Luminal A subtype was the lowest. Multivariate analysis showed that molecular subtypes cant be the predictive factors for this therapeutic scheme (P>0.05) and only HER-2 (P<0.05) was the independent variable in predicting pCR for this therapeutic scheme. Conclusion Molecular subtypes can not independently predict pCR for neoadjuvant chemotherapy regimen containing docetaxel and anthracyclines.     

乳腺癌新辅助化疗的研究进展

近年来,新辅助化疗治疗乳腺癌的概念引起了肿瘤学界极大的兴趣。一系列正在进行的临床研究都希望这一新疗法能够从总体上增加疗效。新的化疗药物、新的影像学检查工具及某些生物学因子正日益引起广大学者的密切关注。基因表达谱也有望对新辅助化疗反应作出预测。本文对以上诸方面分别作了介绍。     

乳腺癌新辅助化疗的研究进展

目的探讨乳腺癌新辅助化疗的研究进展。方法从乳腺癌新辅助化疗的理论基础、临床意义、适用范围、常用药物及方案、疗效预测因子及其与保乳手术、前哨淋巴结活检的关系等方面总结乳腺癌新辅助化疗的研究进展。结果新辅助化疗可降低临床分期,增加保乳手术机会,了解化疗药物敏感性,防止远处转移,但对前哨淋巴结活检的影响存在争议。结论新辅助化疗是乳腺癌全身治疗重要的部分,但在如何选择高效的化疗药物、制订个体化方案、预测治疗效果等方面仍需进一步研究。     

新辅助化疗在乳腺癌的临床应用疗效观察

目的探讨分析乳腺癌新辅助化疗的安全性及临床疗效。方法对收治的120例II~III期乳腺癌进行新辅助化疗。120例患者随机分为A组和B组,A组采用表柔比星单用方案,B组采用表柔比星+多西紫杉醇联合用药方案。化疗4个周期后评价其临床疗效。结果 A组4例患者完全缓解,28例患者部分缓解,总有效率为53.33%;B组13例患者完全缓解,32例患者部分缓解,总有效率为75.00%。表柔比星+多西紫杉醇联合应用明显优于单用表柔比星(P0.05)。结论新辅助化疗可使原发病灶及淋巴结明显缩小,为手术切除创造有利条件,提高手术成功率。     

乳腺癌新辅助化疗后手术时机的选择

<正>乳腺癌的新辅助化疗(NAC)及NAC后的手术时机一直是研究和争论的热点,但就乳腺癌NAC而言,其对病人预后影响的认识基本是一致的。几项大型随机临床试验表明,NAC和辅助化疗的病人在无病生存期(DFS)和总生存期(OS)方面没有显著差异,其中规模最大的试验为NSABP B-18和B-27试验~([1-2])。目前最新公布的中位随访时间16年的研究结果,进一步证实了上述结论,但同时也证实了NAC组保乳率较术后辅助化疗组的疗效有显著差异,NAC可提     

局部进展期乳腺癌新辅助化疗后保乳手术31例报告

目的探讨局部进展期乳腺癌新辅助化疗降期后保乳手术治疗的可行性。方法2002年1月-2005年6月我院接受新辅助化疗后行保乳治疗的31例局部进展期乳腺癌。化疗方案：①TE：表阿霉素60mg／m^2，紫杉醇150mg／m^2，21d为1个周期；②CEF：表阿霉素60mg／m^2，环磷酰胺600mg／m^2，5-FU600mg／m^2，21d为1个周期，共3～4周期。在新辅助化疗完成后，临床体检、B超和钼靶乳房x线检查评估新辅助化疗疗效，符合保乳条件且病人有保留乳房的愿望可接受保乳治疗。手术方式为象限切除或肿块局部广泛切除联合腋窝淋巴结清扫。术后常规行辅助放疔、化疗和内分泌治疗。结果新辅助化疗总有效率（overaul response rate，ORR）90．3％（28／31）；临床完全缓解（complete response，CR）25．8％（8／31），其中病理完全缓解（pathologic complete response，pCR）4例（12．9％，4／31），临床部分缓解（partial response，PR）20例（64．5％，20／31），无进展病例。经过34个月中位随访期（4～46个月），局部复发率6．5％（2／31）；3例术后发生远处转移，转移部位分别为肺、肝脏、脑膜和骨，远处转移率9．7％（3／31），其中1例死亡。对保乳综合治疗结束后满1年的25例进行乳腺外形的评估，外形优16．0％（4／25），良40．0％（10／25），差44．0％（11／25）。结论经新辅助化疗降期后的局部进展期乳腺癌进行保乳手术治疗效果满意，规范化的切除和术后放疗、全身综合治疗是保乳治疗成功的关键。     

新辅助化疗对乳腺癌腋淋巴结及结外侵犯的影响

目的 旨在观察局部进展期乳腺癌新辅助化疗时腋淋巴结及结外侵犯的临床病理学改变.方法 2002年6月-2009年8月南京大学附属第二医院收治的肿块大于5 cm伴同侧腋淋巴结肿大但不融合的86例患者,以患者是否愿意行新辅助化疗分组,A组患者46例,不愿行新辅助化疗,穿刺确诊后行手术治疗,术后病理证实,腋淋巴结转移40例,转移腋淋巴结结外侵犯17例.B组患者40例,自愿行新辅助化疗,穿刺确诊后平均行3个周期新辅助化疗,再行手术治疗,术后病理证实,腋淋巴结转移26例,转移腋淋巴结结外侵犯6例.结果 A组患者淋巴结转移率为86.9%,转移淋巴结并结外侵犯率为36.9%;B组患者淋巴结转移率为65%,转移淋巴结结外侵犯率为15%,两组病例在淋巴结转移率及转移淋巴结结外侵犯率之间存在显著差异,P<0.05.结论 新辅助化疗对于患者的腋淋巴结转移灶有明显作用,减少了淋巴结转移率及转移淋巴结结外侵犯率.     

Accuracy of ultrasonography and mammography in predicting pathologic response after neoadjuvant chemotherapy for breast cancer

Background

Neoadjuvant chemotherapy reduces tumor size before surgery in women with breast cancer. The aim of this study was to assess the ability of mammography and ultrasound to predict residual tumor size following neoadjuvant chemotherapy.

Methods

In a retrospective review of consecutive breast cancer patients treated with neoadjuvant chemotherapy, residual tumor size estimated by diagnostic imaging was compared with residual tumor size determined by surgical pathology.

Results

One hundred ninety-two patients with 196 primary breast cancers were studied. Of 104 tumors evaluated by both imaging modalities, ultrasound was able to size 91.3%, and mammography was able to size only 51.9% (χ²P < .001). Ultrasound also was more accurate than mammography in estimating residual tumor size (62 of 104 [59.6%] vs 33 of 104 [31.7%], P < .001). There was little difference in the ability of mammography and ultrasound to predict pathologic complete response (receiver operating characteristic, 0.741 vs 0.784).

Conclusions

Breast ultrasound was more accurate than mammography in predicting residual tumor size following neoadjuvant chemotherapy. The likelihood of a complete pathologic response was 80% when both imaging modalities demonstrated no residual disease.     

新辅助化疗对局部进展期乳腺癌的临床疗效以及细胞和血管组织学的影响

目的 研究采用TEF方案的新辅助化疗对局部进展期乳腺癌的临床疗效和细胞增殖、微血管密度和组织学分级的影响。方法 24例局部进展期乳腺癌患者接受TEF新辅助化疗二个疗程后进行手术切除,应用免疫组化S-P染色法分别检测24例行新辅助化疗的患者和24例对照组患者手术切除的乳腺癌标本的增殖细胞核抗原(Proliferating cellnuclear antigen,PCNA标记指数以及肿瘤组织的微血管密度(Microvessel Density,MVD),对两组患者的HE染色标本进行组织学分级,并对临床疗效进行分析。结果 新辅助化疗组中临床CR2例,PR21例,NR 1例,病理CR 1例,PR 22例,NR1例。两组比较PCNA标记指数有显著差异(P<0.01),MVD和组织学分级也均有显著差异(P<0.05)。结论 采用TEF新辅助化疗方案近期临床疗效明显,可以显著地抑制乳腺癌细胞的增殖,减少新生血管的生成,降低组织学的分级。     

Ki67预测乳腺癌新辅助化疗效果的临床研究

目的检测接受新辅助化疗的乳腺癌组织化疗前Ki67(细胞增殖核抗原)的表达,探讨其与新辅助化疗效果的关系。方法接受含蒽环类药物新辅助化疗的乳腺癌患者46例,化疗前空心针穿刺获取标本,免疫组化SP法检测乳腺癌组织中Ki67的表达,利用百分数定量Ki67的表达水平,统计学分析Ki67的表达水平与临床病理特征以及新辅助化疗临床效果的关系。结果在Ki67高表达(25%的癌细胞阳性)和低表达(≤25%的癌细胞阳性)的乳腺癌患者中,两组的临床病理特征相似,Ki67高表达组和低表达组的术前化疗临床缓解率分别为85.0%和46.15%,ki67的表达水平与化疗效果有显著相关性(χ2=9.787,P=0.027)。结论新辅助化疗前乳腺癌组织Ki67的表达水平可作为预测乳腺癌新辅助化疗效果的分子指标。     

Breast-conserving surgery using supine magnetic resonance imaging in breast cancer patients receiving neoadjuvant chemotherapy

BACKGROUND: Success of breast-conserving surgery (BCS) following neoadjuvant chemotherapy (NAC) depends on accurate assessment of the initial lesion. We developed a new procedure (NIPR) in which initial naked magnetic resonance images are projected onto the skin before BCS. METHODS: Thirty-five breast cancer patients underwent supine oblique MRI of the operative area. In 20 DCIS patients, the metallic clips were reproduced by projection on the skin using NIPR, and discrepancies between the projection site and clip were measured on X-rays. Fifteen patients (T1;3,T2;8,T3;4 cases) treated with NIPR were compared to 20 (T1;5 , T2;15 cases) treated using the conventional method with regard to excision area and additional excision rate of BCS after NAC. RESULTS: The median discrepancy (linear distance) was 2.6 mm. NIPR significantly reduced the excision area and additional excision rate in T1 and T2 compared to the conventional method (P<0.05). CONCLUSIONS: NIPR is a reliable technique for BCS following NAC with significant reductions in excision area and additional excision rate and superior cosmetic results.     

观察FOLFOX新辅助化疗方案治疗不能切除的进展期胃癌的疗效

目的 研究奥沙利铂联合氟尿嘧啶和亚叶酸钙(FOLFOX)方案术前进行新辅助化疗对术前评估难以进行根治性手术的进展期胃癌患者的临床疗效及不良反应.方法 入组患者均为兰州军区兰州总医院2008年4月-2009年10月收治的16例晚期胃癌而无法行根治手术.新辅助化疗方案为:奥沙利铂130 mg/m~2第1天;氟尿嘧啶500 mg/m~2、亚叶酸200 mg/m~2第1～5天,每3周为1个周期,共2个周期.观察新辅助化疗后原发病灶的变化情况及用药后的不良反应.结果 新辅助化疗后13例患者获得肿瘤减期,疗程结束后4～6周11例进行根治性手术切除.临床完全缓解(CR)2例,部分缓解(PR)10例,疾病稳定(SD)3例,进展(PD)1例,总有效率为75.0%(12/16).不良反应主要为骨髓抑制、腹泻、恶心呕吐、外周神经感觉异常,经对症治疗后均能缓解.结论 奥沙利铂联合氟尿嘧啶及亚叶酸钙的新辅助化疗方案在不能手术切除的进展期胃癌的治疗中,显著提高手术切除率,耐受性良好,值得推广.     

进展期胃癌新辅助化疗后手术时机的选择

进展期胃癌的同手术期化疗、尤其新辅助化疗（NAC）的效果备受瞩目。美国、英国和日本开展的诸多NAC试验结果显示．NAC能够使肿瘤和转移淋巴结缩小．降低T分期和N分期,使不能切除的肿瘤在NAC后实现R0切除,具有良好的改善生存的效果。由于NAC及其方案对不同个体的影响不同,手术时机、手术方案及治疗目标也有所不同。选择低毒、无不良反应及不增加手术风险的NAC方案同然重要,但在充分熟悉了解药物的药理和药代动力学及对人体组织细胞学影响的基础上．对于NAC后的外科手术应谨慎选择和严格质控。     

The effect of neoadjuvant chemotherapy on estrogen and progesterone receptor expression and hormone receptor status in breast cancer

BACKGROUND: Neoadjuvant chemotherapy may decrease tumor volume to allow breast conservation surgery. Its effect on estrogen and progesterone receptor (ER/PR) expression and hormone receptor (HR) status is controversial. METHODS: From February 2001 to July 2002, 56 breast cancer patients treated with neoadjuvant chemotherapy and 56 non-neoadjuvant therapy (control) patients with adequate tissue samples were identified. Quantitative ER/PR expression was analyzed in preneoadjuvant or preoperative core biopsies and final surgical specimens. Changes between the two groups were compared to determine if alterations were due to neoadjuvant chemotherapy or tissue sampling. RESULTS: The ER/PR expression changed in 34 (61%) neoadjuvant chemotherapy patients and 27 (48%) control patients. These expression changes resulted in HR status (positive/negative) alterations in 3 patients (5%) in both groups. Age, histology, chemotherapy regimen, and neoadjuvant response did not predict change. CONCLUSIONS: Hormone receptor status changed in 5% of neoadjuvant chemotherapy and control groups due to tissue sampling. As these changes may impact treatment, HR expression reanalysis in final surgical specimens is recommended.     

High-resolution axillary ultrasound is a poor prognostic test for determining pathologic lymph node status in patients undergoing neoadjuvant chemotherapy for locally advanced breast cancer

BACKGROUND: The purpose of this study was to evaluate the efficacy of high-resolution axillary ultrasound in detecting axillary lymph node metastases after neoadjuvant chemotherapy in patients with locally advanced breast cancer. METHODS: Fifty-three patients with stage II or III breast cancer undergoing neoadjuvant chemotherapy who had a physical examination, high-resolution axillary ultrasound, and axillary lymph node dissection from January 1999 to September 2003 were included in this study. RESULTS: The positive predictive value of the postchemotherapy ultrasound for predicting pathologic nodal involvement was 83%, but the negative predictive value was only 52%. Postchemotherapy physical examination was also poor at predicting pathologic nodal involvement with a positive predictive value of 93% and a negative predictive value of only 58%. CONCLUSIONS: A negative post-neoadjuvant chemotherapy high-resolution axillary ultrasound or physical examination does not predict pathologic node status, and this test has limited value in this setting.