乳腺癌新辅助化疗疗效与分子分型的关系

目的探讨乳腺癌分子分型与表柔比星联合多西他赛（TE）方案新辅助化疗疗效的关系。方法根据纳入和排除标准,共纳入我院2011年5月至2012年12月期间至少接受过3周期TE方案治疗的乳腺癌患者共239例,其各项临床指标均完整。根据免疫组织化学雌激素受体（ER）、孕激素受体（PR）、人表皮生长因子受体2（HER-2）及Ki-67表达水平将患者分为4种亚型,分别为luminal A型、luminalB型、HER-2阳性型和三阴型。分析不同亚型乳腺癌患者的各项相关指标,如病理完全缓解（pCR）率、年龄、月经状态等。结果239例患者中,luminalA型67例（28．03％）,luminalB型84例（35．15％）,HER．2阳性型21例（8．79％）,三阴型67例（28．03％）。4型乳腺癌患者的年龄、月经状态、肿瘤大小、淋巴结状态等临床病理指标差异均无统计学意义（P〉0．05）。三阴型对TE方案的新辅助化疗的pCR率（14．93％）最高,其次依次为luminalB型（7．14％）、HER-2阳性型（4．76％）及luminalA型（1．49％）,差异有统计学意义（P=0．027）。结论三阴型相对luminalA型、luminalB型和HER-2阳性型对TE方案的新辅助化疗治疗更敏感,pCR率最高,治疗时需根据患者不同的分子亚型来选用特定的治疗方案。     

肌层浸润性膀胱癌分子分型新辅助化疗敏感性及预后的差异性研究

国内外指南均推荐所有非转移性肌层浸润性膀胱癌(non-metastatic muscle-invasive bladder cancer,MIBC)患者需在根治性膀胱切除术(radical cystectomy,RC)前接受顺铂为基础的新辅助化疗(neoadjuvant chemotherapy,NAC),从而提高患者的生存率,降低患者病理分期、死亡率和复发风险。但MIBC的部分分子亚型预后差,MIBC的不同分子亚型对NAC具有差异反应,因此,部分患者对NAC反应差或无反应,造成错失手术时机,导致肿瘤进展或转移,无生存获益。通过对MIBC分子分型的差异性研究,使膀胱癌的诊断从传统的组织病理学分型上升到分子病理学层次,进一步加强对同一病理类型膀胱癌的异质性、预后判断,从而为精准个体化的新辅助化疗提供了新的依据。本文将对肌层浸润性膀胱癌分子分型对新辅助化疗敏感性及预后差异进行文献综述,推广MIBC分子分型在临床上的常规化应用。     

乳腺癌分子分型时代的新辅助治疗

在过去的20年中,随着对新辅助治疗模式认识的加深,其应用已不仅局限于局部晚期乳腺癌的降期治疗,而是作为认识肿瘤生物学行为、评估新兴治疗方案疗效的平台,广泛应用于早期乳腺癌的治疗。目前对于新辅助治疗的可选方案,在乳腺癌各版临床指南[1-2]中,均简述为:可参考乳腺癌的术后辅助治疗,进行术前全身系统治疗的方案选择。然而不同于术后辅助治疗,病人在接受新辅助治疗时,对于截然不同的肿瘤负荷,治疗的获益可能存     

血脂相与浸润性乳腺癌分子分型的相关性探讨

目的 探讨血脂相与浸润性乳腺癌分子分型的相关性.方法 选取西南医科大学附属医院乳腺外科2018年1月至2019年6月期间收治确诊为原发性浸润性乳腺癌患者375例,检测其血清总胆固醇(total cholesterol,TC)、甘油三酯(triglycerides,TG)、高密度脂蛋白胆固醇(high-density l...     

乳腺癌分子分型与治疗策略

随着乳腺癌早期诊断及综合治疗水平的提高,乳腺癌发病率日趋升高,其病死率虽有所下降,但仍是女性病死率最高的致死性疾病。相同病理类型及相同临床分期的乳腺癌,即使经历相同的治疗过程其预后仍然有较大差异,表明乳腺癌存在高度的异质性。作为分子高度异质性疾病,沿用的解剖学分期和组织学分类已不能满足其目前的临床诊治需求,尤其缺少能够标志肿瘤生物学行为并对临床治疗提供指导作用的乳腺癌组织学分类方法。分子水平联合组织学分类研究乳腺癌的发病机制、治疗及预后成为当前的研究热点,标志着乳腺癌的治疗进入到个体化治疗的时代。     

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…     

不同分型浸润性乳腺癌与腋窝淋巴结转移的相关性

目的:研究不同分型浸润性乳腺癌与腋窝淋巴结转移的相关性。方法:收集2013年1月—2015年1月于上海新华医院崇明分院接受乳腺癌手术治疗的102例患者。将所有受试者按照免疫组织化学及HER2荧光原位杂交结果的不同分为Luminal A型、Luminal B型、HER2阳性型及三阴性乳腺癌。比较不同分型乳腺癌患者的腋窝淋巴结转移情况、病理参数及预后情况。并以Logistic分析法明确乳腺癌患者预后不良的影响因素。结果:102例乳腺癌患者腋窝淋巴结转移率为34.65%,其中Luminal A型、Luminal B型、HER2阳性型及三阴性乳腺癌的腋窝淋巴结转移率分别为24.00%、41.46%、45.45%及14.29%。不同分型乳腺癌患者的腋窝淋巴结转移率差异无统计学意义(均P>0.05)。肿瘤直径≥5 cm的乳腺癌患者腋窝淋巴结转移率高于<5 cm的患者(P<0.05)。三阴性乳腺癌患者局部复发率高于其他分型乳腺癌患者,且HER2阳性型、三阴性乳腺癌患者的远处转移率均高于LuminalA型、LuminalB型,而三阴性乳腺癌患者存活率均低于其他分型乳腺癌患者(均P&l...     

老年乳腺癌术后辅助化疗对预后的影响

目的探讨老年乳腺癌的术后辅助化疗对预后的影响。方法收集80例Ⅰ~Ⅲ期≥65岁乳腺癌患者的资料,其中接受辅助化疗有47例,未接受辅助化疗有33例,分析两组的临床病理特点和预后特征。结果与未接受术后辅助化疗的患者比较,接受辅助化疗年龄轻的患者较多(P=0.005)、伴有合并症较少(P=0.040)、腋窝淋巴结转移率高(P0.001)、ER/PR阴性率高(P=0.029)、接受放疗概率高(P=0.005);而在肿瘤组织学分级、肿瘤大小、HER2表达、手术方式、内分泌治疗无明显区别(P0.05)。中位随访期为73个月,辅助化疗组与未辅助化疗组相比,无病生存率(DFS)无明显区别(78.7%vs 90.9%,P=0.147),总生存率(OS)也无明显区别(83.0%vs93.9%,P=0.098)。结论老年乳腺癌患者术后辅助化疗的获益不明显,但对于年纪较轻、伴有合并症较少且伴有腋窝淋巴结转移、ER/PR阴性等高风险因素的患者,应全面综合评估患者的耐受性和获益程度选择术后辅助化疗。     

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.     

Magnetic resonance imaging patterns of tumor regression in breast cancer patients after neo‐adjuvant chemotherapy,and an analysis of the influencing factors

The objective of this study was to analyze the patterns of breast tumor shrinkage in patients after neo‐adjuvant chemotherapy (NAC) based on magnetic resonance imaging (MRI), and to evaluate the influential factors. Preoperative breast dynamic contrast‐enhanced MRI was performed on 88 patients before NAC, every 2 weeks during their chemotherapy treatment, and the week before their surgery. The MRI enhancement pattern of the primary tumors was classified into one of four categories based on BI‐RADS‐MRI: type I (postcontrast mass image), II (multiple small masses image), III (postcontrast mass image with peripheral non‐mass enhancement image), and IV (nonmass enhancement image). Multivariate regression and χ² test analyses were employed to establish significant associations. Two kinds of tumor regression patterns were observed: concentric shrinkage was observed in 39 lesions of 88 patients (44.3%), and nests or dendritic shrinkage was observed for the other 49 lesions (55.7%). ER+/HER2?, HER2+, and type I lesions were observed in 23 (62.2%), 21 (63.6%), and 29 (60.0%) patients, respectively, out of 49 nest or dendritic shrinkage pattern lesions. Triple negative breast cancer lesions, and type II, III, and IV lesions were observed in 13 (72.2%), 9 (81.8%), 10 (62.5%), and 10 (76.9%) patients, respectively, out of 39 lesions with a concentric shrinkage pattern. Molecular subtypes (χ²=7.171, P<.05) and the MRI schedule of enhancement (χ²=11.244, P<.05) were significantly associated with the tumor regression patterns. Multivariate analysis showed molecular subtypes (P<.05) and MRI pattern enhancement (P<.05) were significant predictive factors. Molecular subtypes and the MRI enhancement patterns of the primary tumors were significant predictive factors for tumor regression patterns of breast cancer after NAC.     

三阴性乳腺癌综合治疗中化疗方案选择及评价

三阴性（雌激素、孕激素受体与HER-2均为阴性）乳腺癌（TNBC）是具有特殊的生物学行为及临床病理特征的一个乳腺癌亚型。TNBC 对化疗敏感,化疗是可手术以及晚期TNBC病人的主要治疗方法,紫杉类和铂类药物方案可能更为有效,但尚无标准化疗方案。近年来,靶向药物成为TNBC治疗研究的热点,也是未来的研究方向。     

Retrospective comparison of two consecutive cohorts of adjuvant chemotherapy regimens of cyclophosphamide with either docetaxel or paclitaxel in older patients with early breast cancer

Adjuvant chemotherapy with docetaxel/cyclophosphamide (TC) is adopted worldwide as a valuable option for elderly patients with high‐risk early breast cancer. Some studies suggest that paclitaxel may have a better therapeutic ratio than docetaxel. Therefore we have implemented an adjuvant chemotherapy in which docetaxel was replaced by paclitaxel. We report here the retrospective analysis of that cohort and make a safety comparison with an earlier TC cohort in the same target population. This retrospective analysis demonstrates the feasibility of paclitaxel/cyclophosphamide as an alternative, better tolerated adjuvant regimen for elderly patients. Further evaluation and assessment of noninferiority to TC is warranted.     

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。     

Pathologic Tumor Response of Invasive Lobular Carcinoma to Neo‐adjuvant Chemotherapy

Abstract: Neo‐adjuvant chemotherapy is used for locally advanced breast cancer patients with significant variation in tumor response. Our objective is to determine the clinicopathologic effect of neo‐adjuvant chemotherapy on invasive lobular carcinoma. A review of a single‐institution data base of women diagnosed with breast cancer identified 30 patients from 1999 to 2009 with operable invasive lobular carcinoma who received neo‐adjuvant chemotherapy. Patient demographics and clinicopathologic data were reviewed. Cases were reviewed by a single pathologist (NNE). Residual cancer burden class was determined for each case. Median patient age was 50 years (range 25–79). All tumors were hormone receptor positive and clinical stage II or III carcinomas. Most patients (53.3%) had combination anthracycline‐ and taxane‐based chemotherapy. Therapy‐related changes were noted within the tumor bed in 25 (83.3%) patients. Six (30%) of 20 patients with residual axillary disease had therapy‐related nodal changes. There were 11 patients with moderate residual disease (class II) and 18 (60%) with extensive (class III); there were no complete pathologic responses (class 0). Only one patient (3.3%) converted from mastectomy to breast‐conserving surgery. Four (13.3%) patients developed distant metastases; all had pleomorphic‐type, clinical stage III tumors with residual cancer burden III classification and developed distant disease in the 2 years after surgery (range 0–26 months). Median follow‐up time was 29.5 months (range 7–132). Patients with locally advanced pleomorphic‐type lobular carcinoma appear to develop early post‐treatment metastatic disease. Neo‐adjuvant chemotherapy did not appear to have significant impact on the surgical treatment of patients with invasive lobular 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.     

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.     

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.