铂类药物用于三阴性乳腺癌的新辅助化疗

三阴性乳腺癌(triple-negative breast cancer,TNBC)作为乳腺癌的一个亚型,其复发率较高而总生存率低。尽管其对于包含蒽环类和紫衫类药物为基础的新辅助化疗方案反应显著,但预后较差。目前尚未发现专门的分子及化疗药物作用靶点。铂类并非是治疗三阴性乳腺癌的常规用药,本文对铂药物用于三阴性乳腺癌新辅助化疗的现状进行综述。     

乳腺癌组织p53表达与新辅助化疗疗效相关性Meta分析

目的评价乳腺癌组织p53的表达与新辅助化疗疗效的相关性,为乳腺癌的规范化和个体化治疗提供依据。方法计算机检索Cochrane、PubMed、Embase、中国知网、万方和维普等数据库2000-04-2013-11乳腺癌组织p53表达与新辅助化疗的临床研究,按照一定的入排标准将研究方法相似的文献归类整理,原始数据汇总后进行Meta分析和统计处理。结果共纳入22篇相关临床研究,p53表达阳性762例,其中有效478例;p53表达阴性1 094例,其中有效762例。Meta分析结果显示,乳腺癌组织p53表达阳性组与阴性组新辅助化疗的有效率差异无统计学意义,OR=0.69,95%CI:0.44~1.09,P=0.11。亚组分析显示,在蒽环类基础化疗(OR=0.65,95%CI:0.24~1.76,P=0.40)和紫杉类联合化疗(OR=0.70,95%CI:0.40~1.25,P=0.23)中,p53表达的阳性与阴性组间乳腺癌新辅助化疗疗效的差异均无统计学意义;但统一免疫组化阳性标准p53≥10%,则发现p53表达的阳性与阴性组间乳腺癌新辅助化疗有效率差异有统计学意义,OR=0.49,95%CI:0.29~0.82,P=0.006。结论 p53作为乳腺癌新辅助化疗疗效敏感性的指标,只有统一免疫组化阳性标准p53≥10%后,对乳腺癌新辅助化疗疗效才可能有预测作用。     

三阴性乳腺癌表柔比星和环磷酰胺联合紫杉醇周疗新辅助化疗临床观察

目的观察表柔比星和环磷酰胺联合紫杉醇周疗在三阴性乳腺癌(triple-negative breast cancer,TNBC)新辅助化疗中的疗效和安全性。方法2010-01-01-2012-10-31河南省肿瘤医院经空芯针活检结合免疫组化检查诊断为TNBC患者67例,术前接受紫杉醇80mg/m2(静脉滴入,d1、d8和d15)、表柔比星75mg/m2(静脉滴入,d1)和环磷酰胺600mg/m2(静脉推注,d1)化疗,21d为1个周期,共4个周期。根据RECIST实体瘤疗效评价标准及术后病理组织学检查评价疗效,按照WHO抗癌药物不良反应分度标准评价不良反应。结果总有效率为91.0%,临床完全缓解(cCR)43.3%(29/67),部分缓解(PR)47.7%(32/67),疾病稳定(SD)9.0%(6/67),无疾病进展(PD)病例;病理完全缓解(pCR)率为41.8%(28/67)。Ⅲ~Ⅳ度中性粒细胞减少发生率为28.4%(19/67),2例(3.0%)出现中性粒细胞减少性发热。Ⅲ~Ⅳ度贫血、血小板减少、恶心呕吐、腹泻及口腔黏膜炎的发生率分别为14.9%(10/67)、3.0%(2/67)、7.5%(5/67)、4.5%(3/67)和4.5%(3/67)。治疗期间未发生严重心脏毒性病例。3年无病生存率和总生存率分别为73.6%和88.9%。结论表柔比星和环磷酰胺联合紫杉醇周疗用于TNBC的新辅助化疗,近期疗效较好,不良反应可耐受。     

Ki-67与乳腺癌临床病理特征及新辅助化疗疗效的相关性

目的：分析Ki-67与乳腺癌临床病理特征对新辅助化疗（neoadjuvant chemotherapy,NCT）疗效和预后的影响,探讨NCT疗效的预测因素。方法用免疫组化法检测320例局部晚期乳腺癌患者癌组织中ER、PR、HER-2及Ki-67表达状况。进行NCT 4～6个周期后手术。分析临床病理特征与病理完全缓解率（patho-logic complete response,pCR）之间的关系。临床病理参数与疗效分析用χ2检验,影响预后因素用Cox多因素回归分析。结果 Ki-67表达与ER（r=－0.174,P=0.002）和PR（r=－0.132,P=0.019）呈负相关,与HER2（r=0.140, P=0.012）和乳腺肿瘤大小（r=0.132,P=0.019）呈正相关;ER阴性组pCR率显著高于ER阳性组（26.9%vs 7.4%,χ2=22.761,P=0.000）;PR阴性组pCR率显著高于阳性组（22.7%vs 10.9%,χ2=7.950,P=0.005）;Ki-67高表达组pCR率18.0%（41/228）优于Ki-67低表达组8.6%（8/92）（χ2=4.552,P=0.033）;化疗后Ki-67表达下降组pCR率19.8%（48/243）优于未下降组1.3%（1/77）（χ2=15.356,P=0.000）;各分子亚型间化疗疗效差异显著,Luminal A型pCR率为1.4%（1/71）,Luminal B型pCR率为15.3%（25/163）,HER2过表达型pCR率为31.3%（14/45）,三阴性型pCR率为22.0%（9/41）（χ2=20.639,P=0.000）;用Kaplan-Meier法进行生存分析,Ki-67低表达组无病生存时间（DFS）和总生存时间（OS）均优于Ki-67高表达组,两者均为P=0.034。结论 Ki-67高表达患者对化疗更敏感,但预后较差。化疗前Ki-67的表达和化疗后Ki-67变化是影响DFS独立的预后因素。ER、PR、Ki-67指数及分子分型可以作为NCT疗效的预测指标,Ki-67指数与ER、PR、HER2之间存在相关性。     

Accuracy of ultrasound for predicting pathologic response during neoadjuvant therapy for breast cancer

Early assessment of response to neoadjuvant chemotherapy (NAC) for breast cancer allows therapy to be tailored; however, optimal response assessment methods have not been established. We estimated the accuracy of ultrasound (US) to predict pathologic complete response (pCR) using common response criteria and pCR definitions, and estimated incremental accuracy over known prognostic variables. Participants undergoing US after two cycles in the GeparTrio trial randomised to no change in NAC were eligible. US response by World Health Organisation (WHO) criteria (1D or 2D) and Response Evaluation Criteria In Solid Tumours (RECIST) was assessed. Four pCR definitions were applied. Sensitivity (correct prediction of pCR), specificity (correct prediction of no‐pCR) and diagnostic odds ratios (DORs) were calculated. Areas under the curve (AUCs) were derived from logistic regression including patient variables with and without US. In 832 patients, DORs decreased as pCR definitions became less stringent (p = 0.01). For WHO‐2D, DORs were as follows: 4.07 (ypT0,ypN0), 3.75 (ypT0/is,ypN0), 3.14 (ypT0/is,ypN+/?) and 2.65 (ypT0/is/1a,ypN+/?). DORs did not differ between US criteria (p = 0.60). High sensitivity and lower specificity were found for WHO‐2D and RECIST; WHO‐1D was highly specific with low sensitivity. Sensitivity was highest for WHO‐2D predicting ypT0,ypN0 (sensitivity = 81.7%, specificity = 47.6% vs. 42.3% and 80.4% for WHO‐1D). Adding US to models including patient variables (age, T‐stage, histology and subtype) improved AUCs for predicting pCR by 2–3%. In conclusion, US accuracy is highest for predicting ypT0,ypN0, shown to be most prognostic of long‐term survival. WHO‐2D and RECIST maximise sensitivity; WHO‐1D maximises specificity. US modestly improves the prediction of pCR by patient characteristics.     

Effect of adjuvant trastuzumab among patients treated with anti-HER2-based neoadjuvant therapy

Purpose:

To study the impact of adjuvant trastuzumab among patients achieving a pathologic complete response (pCR) after trastuzumab-based neoadjuvant systemic therapy (NST).

Patients and methods:

Patients with primary HER2-positive breast cancer treated with trastuzumab-based NST were categorised according to adjuvant trastuzumab administration and pCR status. Adjuvant trastuzumab became standard of care in 2006, this was the main reason patients in our cohort did not receive adjuvant trastuzumab. Kaplan–Meier was used to estimate survival. A test for interaction between adjuvant trastuzumab and pCR was completed.

Findings:

Of 589 patients, 203 (34.5%) achieved a pCR. After surgery, 109 (18.5%) patients in the entire cohort did not receive adjuvant trastuzumab. Among patients achieving a pCR, 31.3% received adjuvant trastuzumab compared with 68.8% among those who did not achieve a pCR (P=0.0006). Among patients achieving pCR, adjuvant trastuzumab did not further improve overall survival (OS) or relapse-free survival (RFS) (P=0.35 and P=0.93, respectively). Any benefit of adjuvant trastuzumab in OS and RFS among patients without a pCR did not achieve statistical significance (P=0.3 and P=0.44, respectively).

Conclusions:

In this cohort, patients treated with trastuzumab-based NST who achieved a pCR have excellent outcome regardless of whether they received adjuvant trastuzumab.     

奥沙利铂联合卡培他滨新辅助化疗方案在ⅡB～ⅢC期胃癌中的应用

目的：观察奥沙利铂联合卡培他滨方案新辅助化疗治疗进展期胃癌患者的临床疗效、毒副作用及生存状况。方法回顾性分析2011年7月—2012年9月该医院收治的65例局部进展期可切除胃腺癌患者的临床资料。其中33例患者（实验组）完成新辅助化疗后接受开放手术治疗,32例患者（对照组）入院后直接行手术,分析比较两组患者的根治效果、术后并发症情况及生存情况等。结果实验组患者R0切除32例、R1切除1例,对照组患者R0切除24例、R1切除8例,两组比较,差异有统计学意义（χ2＝4．861,P＜0．05）;阳性淋巴结检出数目分别为（4．55±1．48）枚和（6．38±2．27）枚（t＝－3．838,P＜0．05）;淋巴结清扫数目分别为（21．24±2．67）枚和（20．19±2．71）枚及术后并发症发生数分别为3例和3例,两组差异均无统计学意义（P＞0．05）。实验组平均术中失血量（434．29±86．64）mL,对照组为（190．97±47．91）mL,差异有统计学意义（P＜0．05）。实验组患者的中位总生存时间为23．5个月,对照组为17．7个月（P＝0．138）。结论奥沙利铂联合卡培他滨新辅助化疗化疗毒副作用可耐受,可提高进展期胃癌R0切除率,降低淋巴结转移率,延长患者的生存时间。