对老年乳腺癌术后辅助化疗的再认识

乳腺癌是全球女性最常见的恶性肿瘤。年龄与乳腺癌的发病呈正相关,即随着年龄的增加,女性患乳腺癌的风险逐步增高[1]。在乳腺癌高发的欧美发达国家,每8位平均年龄61岁以上的女性中就有1位患乳腺癌[2]。目前,西方国家早已进入老龄化社会;我国也于2000年进入老龄化社会,据国家统计局2010年第6次人口普查数据[3]显示,我国人口平均预期寿命为74.83岁,而且女性的平均预期寿命更是达到77.37岁。根据2005年Althuis等[4]     

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。     

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。     

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。     

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。     

浸润性乳腺癌分子分型与辅助化疗方案选择

随着基因表达谱与基因芯片技术的开展,乳腺癌在分子水平上表现出的高度异质性也逐渐受到关注。不同分子分型的乳腺癌,其流行病学危险因素、疾病自然进展过程以及对全身或局部治疗的反应性都不尽相同;对于乳腺癌的准确分型能够较为精确地反映肿瘤的生物学行为,对于判断预后、制定更具个体化的治疗策略具有深刻的意义。2011年的St.Gallen共识已针对不同的乳腺癌分子分型给出了原则性的治疗建议,标志着乳腺癌的治疗已逐步进入了在规范化多学科综合治疗模式的基础上,倡导个体化治疗的时代。     

Dose-dense chemotherapy for breast cancer

The concept of dose-dense chemotherapy has emerged and is based on the hypothesis that maximal chemotherapy effectiveness can be achieved by scheduling the interval of chemotherapy to correspond to the period of most rapid tumor growth, as predicted by preclinical models. The granulocyte-colony stimulating factor support has permitted the safe delivery of chemotherapy at shorter ("dose-dense") inter-treatment intervals. Several randomized trials have been conducted to test the feasibility and effectiveness of anthracycline and/or taxanes-based dose-dense strategies. They have been associated with a modest impact on disease recurrence and overall survival of patients with early-stage breast cancer. Subset analyses have suggested increased benefits for specific tumor subtypes such as hormone receptor-negative, highly proliferative or HER2 overexpressing tumors. This review article aims to outline the theoretical framework for dose-dense chemotherapy and summarizes the results of several recent clinical trials addressing this concept within neoadjuvant and adjuvant breast cancer treatment and discuss their implications for clinical practice. Further studies are needed to define the optimal regimen and the patient population that will receive the greatest benefit from dose-dense strategy.     

胆管下段癌术后辅助化疗的效果分析

目的 探讨胆管下段癌行根治性胰十二指肠切除术后辅助化疗效果。方法 回顾性分析自2016年1 月至2019 年1 月宁波市医疗中心李惠利东部院区收治的23 例胆管下段癌行根治性胰十二指肠切除术患者的临床资料,根据术后是否接受化疗分为2 组,其中化疗组[GEMOX方案（吉西他滨1 000 mg/m2,d1,d8;奥沙利铂130 mg/m2,d1;3周1疗程）]10例和未化疗组13例,比较分析两组术后生存状况（中位生存时间、12个月生存率、累积生存率及无复发生存率）。结果 化疗组随访1～30个月,5例死亡,5例存活;未化疗组随访6～28个月,5例死亡,8例存活。化疗组中位生存时间为21个月,未化疗组中位生存时间为22 个月（P＞0.05）。化疗组和未化疗组12 个月生存率分别为80%（8/10）和77%（10/13）。两组累积生存率比较,差异无统计学意义（χ2=0.277,P＞0.05）。化疗组中位无复发生存时间为15个月,未化疗组为13个月,两组无复发生存率比较,差异无统计学意义（χ2=0.002,P＞0.05）。结论 以吉西他滨+奥沙利铂为主要方案的术后辅助化疗不能使胆管下段癌R0切除患者明显获益。     

Impact of adjuvant systemic chemotherapy on postoperative survival in patients with high-risk urothelial cancer

BACKGROUND: The objective of this study was to retrospectively investigate the effectiveness of adjuvant combination chemotherapy for locally advanced urothelial cancer. METHODS: Between 1987 and 1998, 56 patients with locally advanced bladder (n = 27) or upper urinary tract (n = 29) cancer (pathological stage T3, T4 or N1, N2 and M0) were treated by radical cystectomy or radical nephroureterectomy and regional lymphadenectomy. Thirty-one patients had lymph node-positive disease and 25 patients did not. Twenty patients underwent adjuvant chemotherapy and 36 patients were observed after surgery. Cox proportional hazards models were used to determine the impact of numerous clinicopathological findings on survival. A subgroup analysis of patients with lymph node-positive disease was conducted to evaluate disease-free survival and overall survival rates. RESULTS: In this series, the median follow-up period was 39 months (range, 4-163) after surgery. Disease-free and overall survival rates of all 56 patients were 45% and 58%, respectively, at 3 years. Only lymph node status was significantly associated with disease-free and overall survival in the multivariate analyses. In a subgroup analysis of patients with lymph node-positive disease, 16 patients who underwent adjuvant chemotherapy had superior disease-free survival compared to 15 patients with no adjuvant chemotherapy (P = 0.0376). CONCLUSION: These findings show that the prognosis of advanced urothelial cancer is significantly associated with nodal status. Furthermore, adjuvant combination chemotherapy has a positive impact on survival in patients with lymph node-positive disease.     

Tubular carcinoma of the breast: prognosis and response to adjuvant systemic therapy

Background : Tubular carcinoma of the breast is an uncommon and usually small tumour, and is thought to have a favourable prognosis. The present study examined the long‐term prognosis of patients with tubular breast carcinoma and the roles of axillary dissection and adjuvant therapy. Methods : Eighty‐six tubular cases were identified from a large worldwide database of 9520 breast carcinoma patients entered into randomized adjuvant therapy trials run by the International Breast Cancer Study Group from 1978 to 1999. These patients were followed for a median of 12 years. Results : Forty‐two (49%) cases were node‐positive, of which 33 (79%) had 1–3 nodes involved. Ten (32%) of the 31 smaller tumours (≤ 1 cm in size) were node‐positive. Patients with node‐positive tubular carcinoma had a significantly better 10‐year relapse‐free survival (P = 0.006) and survival (P < 0.0001) compared with non‐tubular node‐positive cases. Overall survival was similar for node‐positive and node‐negative tubular carcinoma. Overall, 71 patients (83%) received some form of adjuvant systemic therapy. Of the 86 cases, 43 (50%) received more than one course of chemotherapy. There was an 85% decrease in the risk of death for patients who received more than one course of chemotherapy compared to those who did not (hazard ratio 0.15, 95% confidence interval (CI): 0.03–0.82; P = 0.03). Conclusions : Compared to other histological types of breast cancer, tubular carcinoma has a better long‐term prognosis. Adjuvant chemotherapy may further improve prognosis and involvement of axillary nodes may not be an indicator for early death due to breast carcinoma.     

Single Institution trial of anthracycline‐ and taxane‐based chemotherapy for operable breast cancer: The ASTER study

The efficacy of anthracycline‐ and taxane‐based chemotherapy for perioperative treatment of breast cancer (BC) has been established. No superiority of a cytotoxic regimen has been demonstrated, provided that administration of an anthracycline and a taxane is warranted. The ASTER study was designed to investigate the safety of 6 months of perioperative chemotherapy with Doxorubicin and Paclitaxel, followed by Cyclophosphamide, Methotrexate, and 5‐Fluorouracil. ASTER enrolled patients with cT2‐3 N0‐1 or pT1‐2 N1‐3 BC, from November 2008 to August 2011. Treatment consisted of Doxorubicin 60 mg/sm, Paclitaxel 200 mg/sm q21 (AT) for three cycles followed by Cyclophosphamide 600 mg/sm, Methotrexate 40 mg/sm, 5‐Fluorouracil 600 mg/sm d1,8 q28 (CMF) for three cycles, in either neo‐adjuvant or adjuvant setting. All HER‐positive patients received targeted therapy with Trastuzumab for 1 year. Disease‐free and overall survival (DFS and OS, respectively) were estimated according to Kaplan‐Meier method. Three hundred and thirty patients were enrolled, where 77.9% of cases were treated in an adjuvant setting; 65.5% received breast conservative surgery, 72.4% axillary dissection. 75.5% of cases presented estrogen receptor positivity, 66.7% progesterone receptor positivity; 18.5% of patients presented HER2‐positive BC, 16.1% triple negative disease. Twenty‐eight (8.5%) developed grade III‐IV hematologic toxicity; nine patients (2.7%) developed grade III neurological toxicity. Loco‐regional DFS was 99.6% at 1 year, 97.1% at 5 years, 95.9% at 7 years. Corresponding distant DFS was 98.4%, 90.2%, and 88.8%. One, 5, and 7‐year OS was 99.6%, 94.9%, and 91.2%, respectively. Chemotherapy with ATx3→CMFx3 is confirmed safe and effective at 6.7 years follow‐up. These results appear comparable to those reported in regulatory trials of most commonly prescribed anthracycline and taxane‐based regimens.     

Sentinel lymph node biopsy after neo-adjuvant chemotherapy in breast cancer

The timing of sentinel node biopsy in the setting of neo-adjuvant chemotherapy for breast cancer is controversial. Sentinel node biopsy performed after neo-adjuvant chemotherapy may save patients with a nodal response the morbidity of an axillary lymph node dissection. A retrospective review of prospectively collected data compared sentinel node biopsies performed after patients had received neo-adjuvant chemotherapy with patients who had not received neo-adjuvant chemotherapy. Demographic factors, tumor characteristics, and the results of the sentinel node biopsies and completion lymph node dissections (when applicable) were compared. A total of 231 axillary procedures (224 patients) were evaluated. The patients who received neo-adjuvant chemotherapy (NEO; N=52) were younger, had higher grade tumors, were more likely to have a mastectomy, and were more likely to have ER-negative and HER-2/neu positive tumors than the patients who did not receive neo-adjuvant chemotherapy (NON; N=179). The mean clinical tumor size in the neo-adjuvant group was 4.5cm (±1.8) prior to chemotherapy; the post-chemotherapy pathologic size was 1.4cm (±1.3). A sentinel node was identified in all cases. There were no significant differences between the groups in the mean number of sentinel nodes removed (NEO=3.3; NON=3.1; p=0.545), the percentage of positive axillae (NEO=24%; NON=21%; p=0.776) or the mean number of positive sentinel nodes (NEO=1.3; NON=1.5; p=0.627). There was no difference in the percentage of completion lymph node dissections with additional positive nodes (NEO=20%; NON=35%; p=0.462); there was a difference in the number of nodes removed in the completion lymph node dissections (mean NEO=12.0; NON=16.4; p=0.047). Sentinel node biopsy performed after neo-adjuvant chemotherapy appears to be an oncologically sound procedure and may save some patients the morbidity of a complete lymph node dissection.     

Modern surgical treatment of breast cancer

Since the 1950's the treatment of breast cancer has changed substantially. This related surgery has become less disfiguring without either impairing survival or increasing recurrences. Adjuvant chemotherapy has also contributed.     

紫杉类与蒽环类药物联合治疗三阴性乳腺癌疗效分析

目的：比较紫杉类和蒽环类药物联合与单纯蒽环类药物治疗三阴性乳腺癌的疗效。方法：585例三阴性乳腺癌患者中,术后行紫杉联合蒽环类辅助化疗228例,蒽环类辅助化疗357例,分析其复发、转移和生存情况。结果：紫杉联合蒽环类组与蒽环类组患者复发率、转移率与死亡率分别为7.9%与13.2%、21.9%与35.9%、18.0%与28.6%（P＜0.05）,与蒽环类方案相比,紫杉联合蒽环类方案延长了临床II、III期、非特殊型浸润性癌、淋巴结阳性患者的总生存期,提高了总生存率。结论：紫杉类与蒽环类药物联合辅助化疗,对于具有晚临床分期、非特殊型浸润性癌及淋巴结阳性特征的三阴性乳腺癌有显著的治疗效果。     

The effect of adjuvant therapy with or without tamoxifen on the endocrine function of patients with breast cancer

The ovarian and pituitary functions of 64 operable breast cancer patients undergoing adjuvant therapy with cytotoxic chemotherapy and/or tamoxifen were investigated. The post menopausal patients, divided into 3 treatment groups, one with tamoxifen alone, one with tamoxifen and chemotherapy and the other with chemotherapy alone had serum estradiol 17-β (E2) and progesterone levels lower than the evaluable limits. Although there was no significant difference in the level of estrone sulfate (E1-S) between these three groups, the level of lutainizing hormone (LH) and follicle stimulating hormone (FSH) in the patients treated with tamoxifen alone and tamoxifen and chemotherapy were significantly lower than those treated with chemotherapy alone. The decrease in gonadotropin levels induced by tamoxifen treatment was reversible as it appeared after the initiation of tamoxifen and recovered after its cessation. In the premenopausal patients, a group treated with tamoxifen and chemotherapy had significantly higher E1-S, E2 and progesterone levels and significantly lower gonadotropin levels than a group treated with chemotherapy alone or one treated with a cyclophosphamide regimen. These increases in the levels of estrogen and progesterone were also reversible, and induced by tamoxifen. Thus, adjuvant endocrinochemotherapy causes profound alteration in the hypothalamo-pituitary-ovarian axis and therefore, monitoring a variety of hormonal levels is thought to be necessary for assessing the consequences of adjuvant therapy in breast cancer patients, especially in premenopausal patients using tamoxifen.