乳腺癌新辅助化疗应该注意的几个问题

从上世纪70年代开始,乳腺癌术前化疗（即新辅助化疗,NACT）应用于临床,经诸多临床试验证实有效、可行,已成为局部晚期乳腺癌（LABC）及元远处转移炎性乳腺癌（IBC）的常规疗法。近10年来,乳腺癌NACT在国内已逐渐推广应用。近30余年,随着医学生物学研究的不断深入,对乳腺癌有了全新的理解,治疗的策略也随之发生了巨大的变化。从广义上讲,乳腺癌是一种全身性疾病,     

NE方案新辅助化疗治疗局部晚期乳腺癌的临床疗效分析

局部晚期乳腺癌（locally advanced breast cancer，LABC）一般是指乳腺原发病灶较大，手术切除较困难，但没有远处转移的临床Ⅲ期乳腺癌，其区域淋巴结转移率在90％以上，预后较差，如何有效治疗LABC，是临床上需引起重视的课题之一。术前化疗设计的生物学基础是癌细胞增殖可使耐药性细胞增多，早期采用无交叉耐药的化疗，有助于抑制耐药细胞的产生，从而提高化疗疗效。化疗可以使LABC降期以便手术治疗，而表阿霉素与诺维苯联合应用是目前对转移陛乳腺癌化疗较有效的方案。我中心2003年8月至2004年10月采用表阿霉索加诺维苯作为LABC的新辅助化疗方案，治疗LABC患者46例，观察治疗后肿瘤的有效率、手术切除率及药物的安全性，结果报道如下。     

乳腺癌介入性新辅助化疗的研究进展

乳腺癌新辅助化疗（New adjuvant chemothempy，NCT）是指对未发现远处转移的乳腺癌患者在局部治疗之前所给予的全身化疗。其应用在局部晚期乳腺癌（Locally advanced breast canceer，LABC）的疗效已得到公认，但随着研究的不断深入，仍有许多问题尚待解决，为此本文就有关问题的研究进展作一综述。     

局部进展期乳腺癌的新辅助治疗

局部进展期乳腺癌(locally advanced breast cancer,LABC)包括进展期原发乳腺癌、区域淋巴结广泛转移和炎性乳癌。虽然经过积极治疗,患者预后仍然很差。综合治疗包括化疗、放疗、外科手术和新靶向药物的应用已显著提高了其临床疗效。但LABC仍然是临床面临的一个难题,尤其在发展中国家和难以普及乳腺癌筛查的国家。LABC的合理治疗方案需要内科、外科和放疗科之间的多学科讨论制定。作者就LABC目前的治疗现状展开讨论。     

乳腺癌新辅助化疗前后Ki67变化对疗效及预后的意义

目的：探讨乳腺癌新辅助化疗（NACT）前后Ki67表达变化对疗效和预后预测的临床意义。方法：回顾性分析汕头大学医学院附属肿瘤医院2009年12月—2013年9月期间收治的104例乳腺癌NACT后手术的患者。采用免疫组织化学评估配对的化疗前穿刺活检标本和手术切除标本中Ki67的表达情况。根据NACT前后Ki67的变化分为Ki67下降组和Ki67未下降（不变或升高）组,并对两组的临床病理学资料进行比较和生存分析。结果：NACT后Ki67下降组占62.5%（65/104）,未下降组占37.5%（39/104）。NACT前高表达Ki67的患者经NACT后Ki67显著下降（63/91,P < 0.01）。Ki67下降组更容易获得有效的临床效果即达到临床完全/部分缓解（59/65,P=0.005）,且NACT后Ki67下降值与临床疗效相关（r=0.302,P=0.002）。NACT后Ki67下降组的无病生存率明显高于Ki67未下降组,差异有统计学意义（P=0.027）;Ki67下降组的总生存率高于Ki67未下降组,但差异无统计学意义（P=0.171）。结论：乳腺癌NACT后Ki67表达下降可能是疗效和预后的预测因子。     

局部晚期乳腺癌的综合治疗（附199例分析）

我们采用诱导化疗-局部治疗-巩固化疗等综合疗法治疗局部晚期乳腺癌（LABC），并与常规疗法对照，取得了满意效果。现就随访5年的病例小结如下。1资料和方法199例LABC为1986年9月～1989年10月我科收治的女性患者。LABC判定标准为TNM分期中Ⅲ期乳腺癌。分两组。常规疗法（局部治疗后辅助化疗）为A组，89例。诱导化疗-手术或加放疗-巩固化疗为B组，110例。体力情况均为Zubrodo级。两组病人年龄，绝经情况，癌组织学类型，肿瘤ER情况，外科治疗术式的分布情况相似。B组诱导化疗用CMF方案86例，FAC方案24例。CMF：环磷酸胺500mg／m…     

survivin与宫颈鳞癌新辅助化疗和放疗敏感性的相关性研究

目的 探讨survivin与宫颈鳞癌新辅助化疗（NACT）和放射治疗（RT）敏感性的相关性。方法新辅助化疗前后采用免疫组化（SABC法）法,检测32例宫颈鳞癌组织中survivin的表达。结果32例患者化疗前后survivin阳性表达率分别为68．8％（22／32）和56．3％（18／32）,差异无统计学意义（P=0．302）。〈45岁与1〉45岁、Ⅰb～Ⅱa期与Ⅱb～Ⅲb期、高中分化癌与低分化癌、化疗前与化疗后survivin阳性表达率比较均无统计学意义（P〉0．05）。化疗前survivin阳性表达患者NACT与NACT＋RT总体疗效比较,差异均有统计学意义（P=0．030,0．009）;survivin（＋）组和（＋＋）组NACT与NACT＋RT的疗效比较,差异均有统计学意义（P≤0．05）;survivin（-）组和（＋＋＋）组NACT与NACT＋RT的疗效比较,差异均无统计学意义（P≥0．05）。结论宫颈鳞癌survivin表达与患者年龄、临床分期和肿瘤分化程度无明显相关性,NACT和NACT＋RT对不同survivin表达程度患者的疗效有显著性差异,治疗前检测患者sat-vivin表达水平可为预测化疗和放疗敏感性提供客观依据。     

局部进展期乳腺癌新辅助化疗43例临床观察

乳腺癌是女性主要恶性肿瘤之一,早期易发生血行播散,多数患者在就诊时可能已发生周身微小转移,治疗上在控制全身亚临床病灶的前提下再行手术,方有更好的临床疗效。我院于2006年9月～2009年9月对43例局部进展期乳腺癌（locally advanced breast cancer,LABC）患者采用吡柔比星、多西他赛术前联合化疗2—4个周期,取得了较好的近期疗效,现报告如下。     

局部进展期乳腺癌趋化因子受体CXCR4的表达与新辅助化疗疗效的相关性及预后研究

背景与目的:目前已经确立新辅助化疗在局部进展期乳腺癌(local advanced breast cancer,LABC)治疗中的地位,达到病理完全缓解者可提高生存率,但仍有大量患者复发、死亡,而无法从中受益。因此,我们迫切需要从分子水平找到可以预测新辅助化疗效果和预后的指标。目前已经证实趋化因子受体CXCR4与乳腺癌的侵袭和转移有关,然而关于CXCR4能否作为LABC患者新辅助化疗中的疗效指标和预后指标,目前却鲜有报道。本研究中,我们采用紫杉醇联合蒽环类的新辅助化疗方案治疗LABC,同时比较CXCR4低表达和高表达与疗效和远期生存的相关性。方法:对接受4个周期紫杉醇联合蒽环类的新辅助化疗方案进行治疗的86例ⅡB～ⅢB期(参照2002年AJCC乳腺癌TNM分期标准)LABC患者资料进行回顾性分析。用免疫组织化学法检测新辅助化疗前后乳腺癌组织CXCR4的表达,分析新辅助化疗对CXCR4低表达和CXCR4高表达患者的临床、病理疗效及其与远期生存的关系。结果:86例患者中58例(67.4%)为CXCR4高表达,28例(32.6%)为CXCR4低表达,新辅助化疗后,CXCR4高表达49例(57.0%),低表达37例(...     

新辅助化疗BPF方案对食管癌微血管密度及血管内皮生长因子的影响

[目的]评价新辅助化疗（NACT）对食管癌微血管密度（MVD）及血管内皮生长因子（VEGF）的影响。[方法]67例Ⅱb～Ⅲb期经胃镜病理证实的食管鳞状细胞癌患者，随机分两组，新辅助化疗组（NACT组）：42例患者行术前新辅助化疗（BPF方案：氟尿嘧啶500mg／m^2，d1-5,iv；顺铂20mg／m^2，d1-5,iv；平阳霉素8mg，d1、3、5、7、9，im）；25例患者行单纯手术作为对照。应用免疫组化方法检测胃镜活检标本和手术后大体切除标本中MVD及VEGF的表达。[结果]NACT组总有效率（CR＋PR）为69．04％，手术切除率为95，23％。NACT组化疗前与对照组的VEGF阳性率分别为73．80％、68．00％，MVD值分别为46．82±19．07、47．12±16．15（x^2=0．260，P=0．610）；化疗后两者（33.33％，29．06±13．05）与化疗前比较均呈显著下降趋势（P〈0．05）。临床有效病例中，新辅助化疗前21例VEGF表达阳性者，新辅助化疗后仅余8例阳性（x^2=4．461，P=0．035）；MVD值化疗前后比较也有显著性差异。[结论]BPF术前化疗方案可有效提高中晚期食管癌的手术切除率，MVD值和VEGF可作为NACT疗效的评价指标。     

Management of locally advanced breast cancer: evolution and current practice

Locally advanced breast cancer (LABC) accounts for a sizeable number (30-60%) of breast cancer cases and is a common clinical scenario in developing countries. The treatment of LABC has evolved from single modality treatment, consisting of radical mutilating surgery or higher doses of radiotherapy in inoperable disease to multimodality management, which along with the above two included systemic therapy. Neoadjuvant chemotherapy (NACT) has made a tremendous impact on the management of LABC. NACT was initiated to institute systemic therapy upfront at the earliest in this group of patients with a high risk of micrometastasis burden. While NACT did not yield a survival advantage, it has however made breast conservation possible in selected group of cases. Large number of studies and many randomised trials have been done in women with LABC in order to improve the therapeutic decisions and also the local control and survival. With this background we have reviewed various treatment options in patients with LABC which should possibly help in guiding the clinicians for optimal management of LABC.     

MRI技术在乳腺癌诊断中的应用进展

乳腺癌作为女性恶性肿瘤的常见病，其发病率和发病人数表现出逐年递增趋势。伴随诊治技术及方案的改进，乳腺癌的诊治方式、疗效监督及预后评估等各方面都有了显著提升，从而也对乳腺癌临床早期诊断的检出率及分期的准确率有了较高的要求。医学影像技术尤其是 MRI检查在乳腺疾病诊治方面不断取得新突破和新应用，乳腺MRI检查技术的角色和作用显得越发重要。MRI基础及功能序列扫描等多种辅助检查，多角度、全方位提供病灶相关解剖、血流动力学、功能及代谢等信息。因而需要全方面熟悉MRI检查技术在乳腺癌诊治中的应用现状，才能使之合理高效的运用于临床诊断、术前分期、治疗方案选取及疗效评估等各方面。     

多模态超声技术在乳腺癌新辅助化疗疗效评估中的应用

随着诊疗技术的发展，乳腺癌进入多种模式相结合的综合治疗时代，新辅助化疗因具有使乳腺癌降期、提高保乳率等优势，应用日渐广泛。早期准确评估疗效对乳腺癌个体化治疗和预后至关重要。目前常见的超声诊断方式包括常规超声、彩色多普勒超声、超声造影、超声弹性成像、自动乳腺全容积成像等技术，因安全无创、操作简单及重复性强等众多优势，被广泛用于乳腺癌治疗前后的疗效评估。本文主要针对多模态超声成像技术在乳腺癌新辅助化疗疗效评估中的应用进行综述。     

多西紫杉醇联合卡铂或卡培他滨一线治疗乳腺癌肺转移的疗效对比

目的:回顾性对比分析多西紫杉醇分别联合卡铂或卡培他滨一线治疗乳腺癌肺转移的临床效果。方法:收集我院2014年1月至2017年6月间符合乳腺癌切除术后、经蒽环类和／或紫杉类辅助化疗后出现肺转移患者的临床资料，共筛选出65例。其中25例行多西紫杉醇联合卡铂(A组)作为一线解救治疗，40例行多西紫杉醇联合卡培他滨(B组)作为一线解救治疗。每2个疗程后进行效果评价，比较两类不同解救治疗方案对乳腺癌肺转移患者的近期疗效及远期预后。结果:65例乳腺癌肺转移患者中，A组和B组客观有效率（ORR）分别为68.0%和42.5%，差异有统计学意义（P=0.045）。A组和B组平均化疗周期(5.0 vs 4.8)、疾病控制率（DCR）(88.0% vs 82.5%)、中位PFS(13.3 vs 12.2个月)、中位OS(51.4 vs 51.0个月)、肺转移后2年PFS(28.0% vs 24.8%)、5年OS(76.0% vs 43.4%)比较差异均无统计学意义(P=0.577、P=0.377、P=0.978、P=0.989、P=0.955、P=0.672)。两组均出现血液学毒性以及恶心、呕吐、腹泻、手足综合征等不良反应，A组患者中白细胞减少、手足综合征的发生率明显低于B组，差异有统计学意义(P=0.049、P<0.001)。结论:乳腺癌肺转移的预后较差，采用多西紫杉醇联合卡铂化疗方案一线解救治疗乳腺癌肺转移的患者近期疗效较好，不良反应小，是值得推荐的一线化疗方案。但从患者的远期预后来看，两组化疗方案并没有明显改善乳腺癌肺转移患者的预后。     

Breast conservation in locally advanced breast cancer in developing countries: wise or waste

Breast conservation as an additional benefit was beyond the initial expectations of the investigators who pioneered neoadjuvant chemotherapy (NACT). In recent years an increasing number of patients with locally advanced breast cancer (LABC) are being treated with NACT, followed by breast conservation surgery with axillary dissection and radiation as a part of the multimodality management. Breast conservation has not been the standard of care for women with LABC, owing to concerns of increased chances of local recurrence, and possible survival disadvantage and psychological trauma from experiencing a recurrence of malignancy.LABC is still a common form of presentation of breast cancer in developing countries. Strict adherence to treatment protocols and regular follow-ups for years may not be practical for a large majority of patients hailing from the regions most affected by LABC. Defaulters often thus have a heavy price to pay.Hence lies the importance of carefully selecting LABC patients for a breast conservation approach from others that would have a higher risk of locoregional recurrence. Can we extrapolate the lessons learnt in early breast cancer to LABC and offer selected patients with LABC breast conservation therapy? Would the local control and survival results with conservative therapy be comparable to those obtained using mastectomy, or does the increased tumor burden in LABC necessitate ablative surgery in all women? This review aims to address these important questions.     

Neoadjuvant chemotherapy: early response as a guide for further treatment: clinical, radiological, and biological

Neoadjuvant chemotherapy (NACT) was initially developed as a treatment strategy for patients with locally advanced breast cancer to improve operability and locoregional control. Today, NACT has become an equivalent option along with adjuvant treatment, and it is regarded as standard treatment approach for patients with locally advanced cancer because it enables breast-conserving therapy to these patients. In addition, there is increasing information on NACT in operable breast disease that supports its use in routine practice for operable tumor stages. According to the German S3 and AGO guidelines, NACT is indicated for every patient with breast cancer, who would need adjuvant chemotherapy after evaluation of radiological, histological, and clinical prognostic factors. Based on a broad range of clinical studies during the last 10 years, it has been demonstrated that NACT leads to an increasing rate of breast-conserving operations, reduced mortality, and less toxicity. A very important issue is to obtain early information about the responsiveness of the primary tumor to chemotherapy, so that individualized therapeutical strategies can be developed. The decision to proceed with NACT is depending on several considerations including surgical aspects, pretreatment diagnostic evaluations, and efficacy monitoring as well as biological aspects to predict response.     

Taxane and Anthracycline Based Neoadjuvant Chemotherapy for Locally Advanced Breast Cancer : Institutional Experience

Background: The aim of this study was to assess the response rates (clinical and pathological ) with docetaxeland epirubicin combination chemotherapy and its effect on outcome. Materials and Methods: We retrospectivelyanalysed locally advanced breast cancer (LABC) patients who received NACT from January 2008 to December2012 in our tertiary care centre. LABC constituted 37% of all breast cancer cases and 120 patients fulfilled theeligibility criteria. The regimens used for NACT were, six cycles of DEC (docetaxel 75 mg/m2, epirubicin 75 mg/m2, cyclophosphamide 500 mg/m2 on Day 1, 3 weekly) and a sequential regimen (4 cycles of FEC, 5-flurouracil600 mg/m², epirubicin 75 mg/m², cyclophosphamide 600 mg/m² followed by 4 cycles of docetaxel 85 mg/m2).Results: The median age was 47 years (range 23-72). Ninety six ( 80 %) had T4 disease and 90% had clinicallypalpable lymph nodes at diagnosis. The median size of primary tumor at presentation was 5.9 cm. Hormonereceptor positivity was seen in 55% and HER2/neu positivity, in 25%. Triple negative breast cancers constituted25 % of the cases. The overall clinical response rate ( complete or partial ) was 85% and pathological completeresponses were obtained in 15%. Four cases defaulted, 5 patients died of treatment related toxicity and 15%developed febrile neutropenia on DEC. The median duration of follow up was 22 months. The median time torelapse was 20 months and the 3 year relapse free and overall survival rates were 50% and 70% respectively.Conclusions: LABC constituted 37% of all breast cancer cases at our institute. With NACT, pCR was seenin 15% of the cases. Sequential chemotherapy was better tolerated than concurrent anthracyline and taxanechemotherapy with a similar pCR.     

Predicting Response to Neoadjuvant Chemotherapy Using 18F FDG PET-CT in Patients with Locally Advanced Breast Cancer

Objective: The study was aimed to find the utility of 18F FDG PET CT in assessing response to neoadjuvant chemotherapy (NACT) in female patients with locally advanced breast cancer (LABC). Methods: All willing women with biopsy proven LABC, following clinical evaluation underwent baseline 18F FDG PET CT along with mammosonograpy and contrast enhanced computerized chest radiography (CECT). The response was assessed clinically before each cycle of chemotherapy using RECIST criteria. Those who were progressing clinically were offered alternate chemotherapy or radiation or surgery. Clinical responders were re-evaluated with 18F FDG PET CT, mammosonogram and CT chest before surgery. The pathological response as assed with residual cancer burden score was used as gold standard. Results: Of the 30 women eligible, 26 women underwent repeat evaluation and surgery. The mean age was 49 years, 16 women were postmenopausal and 15 tumors were receptor positive. On final histopathology 15 % had completer response and 46 % were non responders. Using a cut off value of 50% of the baseline SUVmax, PET-CT had sensitivity, specificity, positive predictive value, negative predictive value and accuracy of 64%, 75%, 75%, 65%, and 69%, respectively in differentiating pathological responders from non-responders. Conclusion: 18F FDG PET-CT predicted the response with greater accuracy than CT or clinical examination. Hence it can be used to identify non responders early in the course and alternate treatment can be offered to patients.     

In vivo detection of resistance to anthracycline based neoadjuvant chemotherapy in locally advanced and inflammatory breast cancer with technetium-99m sestamibi scintimammography

Neoadjuvant chemotherapy (NACT) is the treatment of choice in patients (pts) with locally advanced (LABC) and inflammatory breast cancer (IBC). To evaluate the role of Tc-99m sestamibi imaging in the prediction of response to NACT and in the in vivo functional detection of intrinsic or acquired chemoresistance, 24 female pts with LABC (n=21) or IBC (n=3) were prospectively studied. Tc-99m scintimammography was performed 1-3 days before treatment (first) and 2-5 days after the completion (second) of NACT (epirubicin and cyclophosphamide for LABC and doxorubicin and vinorelbine for IBC). Three planar images (2 lateral prone and one anterior supine, 10 min/each) were obtained 10 min postinjection and a lateral prone image (10 min) of the affected breast (B) was obtained at 4 h. To calculate the tumor to normal B ratio (TBR), 2 identical irregular regions of interest (ROIs) were drawn around the tumor (T) and in adjacent ipsilateral normal B on both early (E) and delayed (D) prone lateral images. The TBR was obtained as the ratio of the mean counts per pixels in the 2 ROIs. Then Tc-99m sestamibi retention index (RI) in the T was determined by dividing the D-TBR by the E-TBR. Afterwards, NACT response was assessed pathologically or clinically in inoperable disease. Scintigraphic sensitivity for correct prediction of T presence after NACT was 81% (17/21), whereas specificity for correct prediction of T absence was 100% (3/3). In LABC, 3 patients had a pathological complete response: first RI was high (>0.56) in all 3, while no T uptake was visible on the second scintigraphy. Eighteen patients did not show a pathological complete response: in 5, both first and second RI were low (相似文献   

卡培他滨节拍化疗在晚期三阴性乳腺癌维持治疗中的疗效观察北大核心

目的:探讨卡培他滨节拍化疗在晚期三阴性乳腺癌患者维持治疗中的近远期疗效、生活质量以及不良反应。方法:将经联合化疗有效的58例晚期三阴性乳腺癌患者随机分为卡培他滨节拍化疗组和卡培他滨常规剂量组两组,每组患者各29例。节拍化疗组患者给予卡培他滨节拍化疗,常规剂量组患者给予常规剂量卡培他滨化疗。治疗2个月后评价近期疗效,每个月评价不良反应,并统计两组患者的中位疾病进展时间、中位生存时间、1年生存率、2年生存率和生活质量的变化。结果:58例患者均可评价疗效。节拍化疗组患者中CR 0例,PR 5例,SD 22例,PD 2例,客观缓解率(ORR)和疾病控制率(DCR)分别为17.2%和93.1%;常规剂量组患者中CR 0例,PR 6例,SD 20例,PD 3例,客观缓解率(ORR)和疾病控制率(DCR)分别为20.7%和89.7%。两组患者的ORR和DCR相比差异无统计学意义(P>0.05)。节拍化疗组患者的中位肿瘤无进展生存时间(PFS)为7.1个月,与常规剂量组患者(6.9个月)比较,差异无统计学意义(P>0.05);节拍化疗组患者的1年、2年生存率分别为72.4%、58.6%,与常规剂量组患者(69.0%、55.2%)比较,差异无统计学意义(P>0.05)。生活质量改善方面,节拍化疗组患者显著优于常规剂量组患者(P<0.05);节拍化疗组患者的主要不良反应为骨髓抑制、消化道反应和手足综合征等,均以Ⅰ-Ⅱ度为主,均可耐受,常规剂量组患者的消化道反应、骨髓抑制、手足综合征等不良反应的发生率和严重程度均显著高于节拍化疗组(P<0.05)。结论:卡培他滨节拍化疗作为晚期三阴性乳腺癌患者的维持治疗,其近远期疗效与常规剂量维持化疗相当,同时可提高患者生活质量,不良反应轻且发生率低,值得临床推广应用。