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。     

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。     

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。     

新辅助化疗对局部晚期乳腺癌的疗效分析

目的探讨新辅助化疗对局部晚期乳腺癌的疗效。方法对56例行新辅助化疗的局部晚期乳腺癌患者的临床资料进行总结分析。56例患者中ⅢA期30例，ⅢB期15例，ⅢC期11例。采用AC方案（环磷酰胺600mg/m^2静脉滴注，阿霉素60mg/m^2或表阿霉素90mg/m^2静脉滴注，第1日，21d为1个周期）或ET方案（表阿霉素90mg/m^2静脉滴注，第1日；多西他塞75mg/m^2静脉滴注，第2日；地塞米松16mg/d，第1-3日口服，21d为1个周期）。化疗3-4个周期后观察疗效，结果全部患者临床有效率（完全缓解＋部分缓解）为71.5%（40/56例），临床获益率（完全缓解＋部分缓解＋病情稳定）为95.4%，病理完全缓解率8.9%（5/56例）。38例（67.9%）重获根治手术机会，中位随访时间40个月，总生存率为62.5%（35/56例），无瘤生存率为39.3%（22/56例）。结论新辅助化疗能降低局部晚期乳腺癌术前TNM分期，使部分患者重获根治性手术机会。     

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     

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悸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。虽然理论上可更大地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生存率方面尚无临床定论。     

乳腺癌新辅助化疗后腋窝淋巴结的变化

目的评价新辅助化疗对乳腺癌腋窝淋巴结的影响。方法45例Ⅱ、Ⅲ期乳腺癌接受新辅助化疗后手术(新辅助化疗联合手术组),根据体检、B超及钼靶像计数腋窝淋巴结总数和阳性、阴性淋巴结数,与未行新辅助化疗直接手术治疗的79例乳腺癌(直接手术组)比较,观察腋窝淋巴结的变化。结果新辅助化疗联合手术组检出腋窝总淋巴结和阳性淋巴结为(16.9±5.9)枚和(2.5±2.2)枚,显著低于直接手术组的(20.8±8.0)枚和(3.9±3.0)枚(t=-2.856,P=0.005;t=2.790,P=0.006),2组阴性淋巴结分别为(14.4±5.4)枚和(16.7±7.0)枚,无统计学差异(t=-1.904,P=0.055)。新辅助化疗联合手术组40例随访6~19个月,平均10个月;直接手术组67例随访7~21个月,平均12个月,2组各有4例复发。结论乳腺癌经新辅助化疗后行腋窝淋巴结清扫所检出的淋巴结总数和阳性淋巴结数减少。     

乳腺癌新辅助化疗进展

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、制定个体化治疗方案、预测治疗效果仍需进一步研究。笔者将从新辅助化疗的意义和适应人群、病理完全缓解作为预后指标的标记物、药物和方案的选择、不同分子分型的新辅助化疗4个方面进行综述。

     

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肿瘤的综合治疗是指医师根据肿瘤的特点和病人的特征 ,合理地应用多种治疗措施 ,以提高肿瘤治疗效果和 (或 )改善病人的生活质量。综合治疗模式在现代乳腺癌的治疗中得到了淋漓尽致的发挥。上世纪 70年代Fisher提出了“乳腺癌一开始就是一个全身性的疾病”的观点 ,从而为乳腺癌全身辅助治疗以及缩小范围的手术治疗提供了理论基础。不久乳腺癌术后辅助化疗和保留乳房治疗的疗效相继被美国外科辅助乳腺计划(简称NSABP)以及欧洲的大样本临床试验所证实 ,从而标志着乳腺癌综合治疗时代的来临。在这场变革中 ,受益最多的还是可手术乳腺癌病人…     

Sentinel node biopsy after neoadjuvant chemotherapy for breast cancer

BACKGROUND: After neoadjuvant chemotherapy, while results of sentinel node biopsy (SNB) are encouraging, conditions that may affect sentinel node (SN) detection and false negative rates with respect to clinical and pathological tumor response after neoadjuvant therapy require investigation. METHODS: Thirty-four patients with clinical stage I, II and IIIA invasive breast cancer underwent neoadjuvant chemotherapy with doxorubicin/cyclophosphamide or doxorubicin/cyclophosphamide and docetaxel/segmental resection, SNB, and axillary node dissection (AND). RESULTS: SNs were found in 31 of 34 patients (91.2%). SNs were found in 20 of 21 patients (95.2%) with complete clinical tumor response, it was positive in 40% and no false negatives occurred. SNs were found in 11 of 13 patients (84.6%) with partial or no clinical tumor response; in four patients (33%) the SN was positive and no false negative nodes were found. Seven patients had complete pathological tumor response. SNs were found in six of these patients (85.7%). The SN was positive in 1 of 6 patients (16.7%) with no false negative. In 25 of 27 patients (92%) with partial or no pathological tumor response, the SN was identified. Eleven of these patients (44%) had positive nodes with no false negatives. CONCLUSIONS: SN identification rate and accuracy after neoadjuvant chemotherapy for breast carcinoma were extremely good however there is potential for inaccuracy after less than complete pathological tumor response. Further evaluation of SNB in larger clinical trial is warranted prior to accepting this approach as a standard care.     

如何提高乳腺癌新辅助化疗的效果

乳腺癌新辅助化疗的兴起与发展不仅使不可手术的局部晚期乳腺癌(locally advanced breast cancer，LABC)和炎性乳腺癌(IBC)变为可手术切除．而且能使可手术的乳腺癌降低临床分期，缩小了乳腺癌手术切除的范围，提高了保乳手术的成功率。这在乳腺癌外科治疗发展史上所起的作用具有划时代意义，在乳腺癌化疗史上是一新的里程碑。     

Sentinel lymph node mapping following neoadjuvant chemotherapy for breast cancer

The purpose of this study was to evaluate the feasibility of sentinel lymph node mapping in patients undergoing neoadjuvant chemotherapy for breast carcinoma prior to lumpectomy or mastectomy and sentinel lymph node mapping followed by complete axillary dissection. A retrospective analysis of 14 patients from February 1998 to July 2000 with stage I to stage IIIB breast cancer diagnosed by core biopsy underwent neoadjuvant chemotherapy (doxorubicin/cyclophosphamide) prior to definitive surgery, including lumpectomy or mastectomy and sentinel lymph node mapping, followed by full axillary dissection. Thirteen of 14 patients had successful sentinel lymph node identification (93%), and all 14 underwent full axillary dissection. An average of 2.2 sentinel nodes and a median of 16 axillary lymph nodes (including sentinel nodes) were found per patient. Of the 13 patients in whom a sentinel lymph node was identified, 10 were positive for metastases (77%). Only 4 of the 10 had further axillary metastases (40%). Three patients had negative sentinel lymph nodes shown by hematoxylin and eosin and cytokeratin stainings and had no axillary metastases (0% false negative). The single patient in whom a sentinel lymph node could not be identified had stage IIIA disease with extensive lymphatic tumor emboli. Sentinel lymph node mapping is feasible in neoadjuvant chemotherapy breast cancer patients and can spare a significant number of patients the morbidity of full axillary dissection. Further study to evaluate sentinel lymph node mapping in this patient population is warranted.     

乳腺癌新辅助化疗后前哨淋巴结活检术的研究

目的 探讨乳腺癌病人新辅助化疗后前哨淋巴结活检的可行性。方法对2003年11月至2004年10月住院治疗中的57例Ⅱ、Ⅲ期乳腺癌病人行新辅助化疗后，临床检查腋窝淋巴结阴性行前哨淋巴结活检术（SLNB）。结果57例中检出前哨淋巴结（SLN）53例，检出率93．0％。SLN对腋窝淋巴结状况预测的敏感性为89．7％，特异性为100．0％，准确性为94．3％，阳性预测值为100．0％，阴性预测值为88．9％，假阴性率为5．7％。肿瘤对化疗反应为CR（完全缓解）、PR（部分缓解）和SD（稳定）的SLN检出率分别为100．0％、96．7％和70．0％（P〈0．01）。SLN假阴性3例均为腋窝淋巴结转移数〉4个者。结论Ⅱ、Ⅲ期乳腺癌实施新辅助化疗后。行SLNB可获得与早期乳腺癌SLNB相似的效果。     

Ultrasound-based prediction of pathologic response to neoadjuvant chemotherapy in breast cancer patients

BackgroundAccuracy in predicting pathologic response to neoadjuvant chemotherapy (NACT) in breast cancer is essential for the determination of therapeutic efficacy and surgical planning. This study aimed to assess the precision of ultrasound (US) for predicting pathologic complete response (pCR = ypT0) after NACT.MethodsThis retrospective mono-center study included 124 invasive breast cancer patients treated with NACT. Patients received US before and after NACT with documentation of clinical partial response (cPR) and clinical complete response (cCR). Post-operatively, the pathologic response was defined as absence of tumor cells (ypT0), presence of non-invasive tumor cells (ypTis) or invasive tumor cells (ypTinv). Sensitivity and specificity of US as well as false negative rate (FNR), negative predictive value (NPV) and positive predictive value (PPV) were analysed for receptor subtypes. A multivariable logistic regression model assessed the influence of patient- and tumor-associated covariates as predictors for pCR.Results50 patients (40.3%) achieved pCR, 39 (78.0%) had a corresponding cCR. Overall sensitivity was 60.8% and specificity 78.0% for US-predicted remission. NPV and FNR differed substantially between subtypes. NPV was highest (75.0%) in triple negative (TN) subtype, while FNR was low (37.5%). Therefore, pathological response was most accurately predicted for TN cancers. NPV for human-epidermal-growth-factor-receptor-2-positive/hormone-receptor-positive (HER2+/HR+) was 55.6%, for HER2+/HR- 64.3% and for HER2-/HR+ 16.7%, FNRs were 40.0%, 71.4% and 32.3%, respectively. Receptor subtypes impacted pCR significantly (p-value: 0.0033), cCR correlated positively with pCR (p-value: 0.0026).ConclusionUS imaging is insufficient to predict pCR with adequate accuracy. Receptor subtypes, however, affect diagnostic precision of US and pathologic outcome.