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。     

可手术乳腺癌系统性辅助化疗

从上个世纪50年代Fisher等提出乳腺癌是一种全身性疾病开始,乳腺癌系统性辅助治疗在乳腺癌治疗中的地位就开始 得到广泛的重视,乳腺癌辅助性化疗的研究结果显示,辅助性 化疗可使乳腺癌死亡率下降约25%,这些研究结果奠定了辅助 性治疗在乳腺癌治疗中的重要地位,乳腺癌的治疗重点已从以 往的单纯性手术治疗向含系统性治疗在内的综合性治疗发展。 一、新辅助化疗 新辅助化疗指对非转移性的肿瘤,在应用局部治疗前进行 的系统性的辅助性细胞毒性药物治疗。由于各种文献报道中 对新辅助化疗的描述角度不同,这种…     

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。     

淋巴结阴性乳腺癌的辅助化疗

淋巴结阴性乳腺癌是否需要辅助化疗或什么样病人应给予化疗 ,这是乳腺癌综合治疗的热点问题 ,现就有关的几个方面谈一些个人的体会。一、淋巴结阴性乳腺癌的自然病程及影响其预后的因素综合文献资料 ,在淋巴结阴性的乳腺癌病人中有约 70 %单纯通过局部治疗 (手术或加放疗 )而治     

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。     

乳腺癌新辅助化疗进展

１概述全身性化疗用于乳腺癌的综合治疗已有４０多年历史，最初被用于杀灭由于手术操作引起的播散的癌细胞，故只在术后短期使用。７０年代以后，随着概念的更新，认为乳腺癌是一种全身性疾病，乳腺癌在诊断时可能已存在亚临床的微小转移而导致手术治疗的失败。辅助化疗的...     

循环肿瘤细胞在乳腺癌新辅助化疗中的应用进展

·综 述·     

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。     

Late effects of adjuvant chemotherapy adumbrate dormancy complexity in breast cancer

BackgroundDormant avascular micrometastases and single, or small groups of, non-proliferating cells are currently assumed to explain the multipeak dynamics of distant metastases (DM) following primary breast cancer surgical removal.MethodsThe hazard rate pattern for DM was analysed in 1518 premenopausal node-positive patients, enrolled in a series of randomized clinical trials on early breast cancer, which were carried out in Italy and Belgium. Patients underwent surgery alone (n = 397) or surgery plus adjuvant chemotherapy (n = 1121) and the minimal follow up was 15 years.ResultsThe DM hazard rate for patients undergoing surgery alone displayed two early sharp peaks at 9 and 33 months, a wide intermediate one spanning from about 50 to 90 months and a late peak at 115–120 months. Adjuvant chemotherapy was associated with a prominent reduction of the two early peaks leaving a residual one at about 18 months and a reduction of the intermediate peak leaving two small peaks at about 50 and 80 months. The late peak remained unchanged.ConclusionsPresent results reveal the ability of adjuvant chemotherapy to reduce not only the rate of early relapses, but also the rate of intermediate relapses at about the sixth year of follow up. Adjuvant chemotherapy is not impacting on the development of metastases underlying the late peak detected at the tenth year. These findings suggest the existence of a previously unknown dormancy state that, at the primary tumour surgical removal, results in evolving chemo-sensitive metastatic processes, and, moreover, of a later chemo-refractory dormancy state.     

Randomized trial of adjuvant chemotherapy after curative resection for gastric cancer

BACKGROUND: The aim of the study was to evaluate the efficacy of adjuvant chemotherapy on survival after resection for gastric cancer. METHODS: Patients were enrolled if they underwent resection of gastric cancer but had lymph node or serosal involvement or both. Surgical resection was either total or partial gastrectomy according to the site of the tumor, and surgeons were allowed to perform either D1 or D2 gastrectomy. The subjects were random assigned in two treatment groups as follows: surgery alone as the control group, or surgery and adjuvant chemotherapy. Nine cycles of 5 days protocol every 4 weeks was proposed to the patients of the chemotherapy group. The protocol included a daily administration of 200 mg/m(2) of folinic acid, 5-fluorouracil (375 mg/m(2) during the first session increasing 25 mg by session until reaching 500 mg/m(2)) and CDDP 15 mg/m(2). Two hundred patients were required. Kaplan-Meier survival curves were compared according to the log-rank and the Mantel-Haenszel methods. RESULTS: In all, 205 patients were enrolled in the study; 104 had surgery alone and 101 had surgery and adjuvant chemotherapy. The patients' characteristics were similar except for the mean age, which was 4 years less in the control group. Because of toxicity, 54% of the patients stopped the protocol before the end of the nine courses, and 46% of the patients received the nine courses including 32% with a decreased dose and 14% with a full dose. The 5-year survival rate was 39% in the control group and 39% in the chemotherapy group. CONCLUSIONS: This protocol of adjuvant chemotherapy failed to improve the 5-year survival after resection for gastric cancer.     

Achieving optimal dose intensity with adjuvant chemotherapy in elderly breast cancer patients: a 10-year retrospective study in a UK institution

The study was to determine if breast cancer patients aged 65 and above could be given adjuvant chemotherapy safely while achieving an acceptable relative dose intensity of at least 85%. We identified all patients aged 65 and over who received adjuvant chemotherapy over the 10 year period, November 1999 to October 2009, and determined the proportion that achieved a relative dose intensity of at least 85% as well as the tolerability of their treatment. A total of 101 patients were identified, with a median age of 69 years (range 65-78).Of these, 25.7% of patients had at least one major comorbidity, 84.2% had a tumor size of 5 cm or less, 73.3% were node positive and 58.4% were hormone receptor positive. The chemotherapy regimens used were AC (Doxorubicin and Cyclophosphamide), FEC (Fluorouracil, Epirubicin, and Cyclophosphamide), CMF (Cyclophosphamide, Methotrexate, and Fluorouracil) and ECMF (Epirubicin followed by CMF). Seventy-nine patients (78.2%) achieved the relative dose intensity of at least 85%. With respect to toxicity, 11.9% of patients developed febrile neutropenia and 23.8% of patients required hospital admission during the treatment period, but there were no treatment-related deaths in the group. A significant proportion of patients aged 65 and above achieved the intended dose intensity of at least 85% over this 10-year period, with manageable toxicity levels. This supports the use of these regimens as adjuvant chemotherapy for breast cancer in this age group.     

绝经前乳腺癌术后辅助治疗对月经的影响

目的探讨乳腺癌术后辅助治疗对月经的影响。方法回顾性分析2014年9月至2015年2月在我院乳腺外科门诊随诊的216例绝经前乳腺癌患者资料。探讨不同的术后辅助治疗(仅接受化疗、仅接受他莫昔芬治疗、化疗联合他莫昔芬治疗)对月经状态的影响,并对接受术后辅助化疗患者出现化疗诱导闭经的相关因素进行探讨。结果术后接受辅助化疗的患者中超过半数(58.3%)出现闭经;仅接受他莫昔芬治疗的患者极少(3.6%)出现闭经,但近半数(43.9%)出现月经不规律;化疗诱导闭经的发生与年龄、化疗方案及是否同时接受他莫昔芬内分泌治疗有关(P0.05),年龄40岁、蒽环为主的化疗方案及接受他莫昔芬治疗均增加化疗诱导闭经的发生率(P0.05);月经能否恢复与年龄有关(P0.05),年龄40岁增加化疗诱导长期性闭经的发生率(P0.05),而与化疗方案、是否接受他莫昔芬治疗无关(P0.05);短暂性闭经患者月经恢复时间平均为(8.0±2.5)个月,超过12.9月者几乎不再恢复月经。结论术后辅助化疗可能导致闭经,年龄越大、蒽环为主化疗及同时接受他莫昔芬治疗者越容易发生;仅接受他莫昔芬内分泌治疗患者极少出现闭经。     

Four cycles of docetaxel and cyclophosphamide as adjuvant chemotherapy in node negative breast cancer: A real-world study

IntroductionThe optimal number of cycles of adjuvant docetaxel and cyclophosphamide (DC) in patients with node negative breast cancer is not known. We aimed to analyse the survival outcomes of patients with node negative and human epidermal growth factor receptor (HER2)-negative breast cancer treated with four cycles of DC.MethodsPatients with node negative and HER2-negative breast cancer treated with four cycles of DC after surgery in a large Canadian province from 2008 to 2012 were identified. We analysed the 4-year and 9-year invasive disease free survival (iDFS) and overall survival (OS). Cox regression models were constructed to examine the associations of clinical characteristics with survival outcomes.ResultsA total of 657 patients were eligible for the current analysis. The median age was 53 years and 71.2% of patients had hormone receptor-positive breast cancer. Approximately three-fourths of patients had grade III tumours. At a median follow-up of nine years, the 4-year iDFS and OS were 91.0% and 95.5% and the corresponding 9-year rates were 80.5% and 88.0%, respectively. On multivariable Cox regression analysis, grade III tumour predicted worse iDFS (hazard ratio [HR], 2.15; 95% confidence interval [CI], 1.09–4.21; P = 0.026) and OS (HR, 3.15; 95% CI, 1.18–8.45; P = 0.022).ConclusionsAdjuvant chemotherapy with four cycles of DC in a select population of node negative breast cancer was associated with encouraging long-term survival. In the absence of a randomized comparison between four and six cycles of DC, this study presents real-world evidence to consider four cycles of DC as a reasonable option.     

Time to initiation of neo‐adjuvant chemotherapy for breast cancer treatment does not influence patient survival: A study of US breast cancer patients

Delays in the initiation of adjuvant chemotherapy or radiation therapy are associated with worse outcomes in patients undergoing treatment for breast cancer. However, the impact of the time to initiation of neo‐adjuvant chemotherapy (NAC) on patient outcomes has not previously been studied. The purpose of this study was to determine whether delays in NAC initiation impact patient survival. The National Cancer Database was queried for women ≥ 18 years old who underwent NAC within 6 months of being diagnosed with stage I‐III invasive breast cancer in 2010‐2011. ER+ or PR+, Her2? cancers were excluded from analysis. Multivariable Cox proportional hazard modeling was used to evaluate the relationship between time to NAC, sociodemographic, diagnosis, and treatment factors with patient survival. The median age of the 12 806 women included in this study was 52 (range 21‐90) with 62% presenting with cT2 disease and 62% with nodal involvement. Half of the women (50%) had triple negative, 30% ER/PR+Her2+ and 20% ER?PR?Her2+ cancers. The median time to starting NAC was 4 weeks (range 0‐26) for all subtypes. Time to NAC initiation was not associated with a difference in survival for triple negative or Her2+ cancers. Delays from diagnosis to starting NAC are not associated with worse survival for patients with Her2+ or triple negative breast cancer. This study demonstrates that the majority of women in the modern era start NAC in a timely fashion and delays in starting NAC within 6 months of diagnosis do not impact long‐term patient outcomes.     

辅助化疗对乳腺癌患者骨密度的影响

目的观察辅助化疗对乳腺癌患者骨密度的影响。方法选取2015年3月至2016年3月就诊宣武医院普外科并行辅助化疗的乳腺癌患者71名,绝经前32人,绝经后39人,根据疾病采用不同化疗方案(EC、FEC、TC、EC-T),患者化疗前均进行骨密度的检查,同时在化疗结束后再进行骨密度的检查。结果在绝经前患者,化疗导致患者腰椎骨密度下降,且患者基础BMI越高,骨密度下降越快;在绝经后患者,化疗导致患者股骨骨密度的下降,与患者的基础BMI关系不大。结论化疗使乳腺癌患者骨密度下降,骨健康受损,且与绝经前患者的BMI相关。     

Concurrent versus sequential adjuvant chemo-endocrine therapy in hormone-receptor positive early stage breast cancer patients: a systematic review and meta-analysis

BackgroundAlthough in clinical practice adjuvant chemotherapy (CT) and endocrine therapy (ET) are administered sequentially in patients with hormone-receptor positive breast cancer, the optimal timing, i.e. concurrent or sequential administration, of these treatments has been scarcely investigated. To better clarify this issue we conducted a systematic review and meta-analysis of randomized studies comparing these two modalities of administrations in terms of disease-free survival (DFS) and overall survival (OS).MethodsRelevant studies were identified by searching PubMed, Web of Knowledge and the proceedings of the major conferences with no date restriction up to March 2016.The summary risk estimates (pooled hazard ratio [HR] and 95% confidence intervals [CI]) for DFS and OS were calculated using random effect models (DerSimonian and Laird method).ResultsA total of three randomized studies were eligible including 2021 breast cancer patients. Overall, 755 DFS events were observed, 365 in the sequential arm and 390 in the concomitant arm, with a pooled HR of 0.95 (95% CI = 0.76 to 1.18, P = 0.643).No association between timing of treatment and OS was observed (HR = 0.95; 95% CI = 0.80 to 1.12, P = 0.529).ConclusionOur pooled analysis showed no association between the timing of administration of adjuvant CT and ET and DFS and OS in breast cancer patients candidates for both adjuvant treatments. Because of the small number of published trials, the lack of data on the timing with modern adjuvant treatments, i.e. taxane-containing CT and aromatase inhibitors, this topic remain still controversial and requires further studies to be clarified.     

乳腺癌治疗的新进展

【摘要】〓乳腺癌是女性常见的恶性肿瘤。随着医学技术的发展以及乳腺癌早期诊断率的提高,乳腺癌的治疗由最早的乳腺癌根治术(包括全乳切除)发展为以保乳手术为主的手术治疗,同时辅助以化疗、内分泌治疗、放疗、靶向治疗及免疫治疗等综合治疗。本文将对乳腺癌的治疗进展进行综述。     

The incidence of symptomatic thromboembolism in patients receiving adjuvant anthracycline-based chemotherapy for early stage breast cancer

Thromboembolism is a well recognised complication of systemic chemotherapy and cancer. Its incidence is frequently not reported in clinical trials of adjuvant chemotherapy for early stage breast cancer. Our own experience suggested that thromboembolic complications were common and we undertook a retrospective review of consecutive patients receiving adjuvant chemotherapy to determine the incidence and morbidity/mortality of this complication.A total of 280 consecutive patients were identified who had received adjuvant ECMF chemotherapy between January 2001 and February 2007. Thromboembolic events occurred in 21 patients (7.5%). Events were distributed across chemotherapy cycles, but were more common during CMF chemotherapy (18 cases vs 3 cases). Patients over the age of 60 years appeared to be at particular risk of thromboembolism with an event rate of 27% (15/56 patients). Thromboembolic events were associated with dose delays and cessation of chemotherapy in some patients. With a median follow up of 28 months there is no significant difference in the incidence of breast cancer recurrence (16.7% vs 14.3%, p = 0.9) or overall survival (89.5% vs 89.9%, p = 0.8) between patients who experienced a thromboembolic event during adjuvant chemotherapy and those who did not. Based on the incidence of thromboembolism in our unselected patient population we believe that further prospective studies are indicated seeking to identify those patients at increased risk of this important complication who might benefit from thromboprophylaxis.