生物学因子预测乳腺癌新辅助化疗疗效新进展

乳腺癌新辅助化疗已成为治疗乳腺癌的重要手段之一,但其疗效缺乏有效的预测方法。本文从生物学因子角度总结了预测乳腺癌新辅助化疗疗效的因素,发现HER-2/neu、BRCA1/2、p53、ER/PgR等生物学因子对于新辅助化疗的疗效有一定的预测价值,并且对于不同的化疗方案的预测价值可能不同。这对乳腺癌新辅助化疗的选择有一定的参考价值。     

乳腺癌患者新辅助化疗后ER、PR、HER2、Ki67表达变化及临床意义

目的:研究乳腺癌患者在新辅助化疗后ER、PR、HER2、Ki67的变化及临床意义。方法:选择2012年1月-2017年12月至我院进行乳腺癌新辅助化疗的患者176例进行临床研究。所有患者化疗前及术后行经B超引导下核芯针穿刺取病理活检,检测ER、PR、Ki67、HER2的表达,分析其变化情况。结果:176例乳腺癌患者新辅助化疗前ER阳性为57例,新辅助化疗后ER阳性为69例,新辅助化疗前ER阴性为119例,新辅助化疗后ER阴性107例;新辅助化疗前后状态改变了34例(19.32%),其中12例新辅助化疗前ER阴性转变为ER阳性,22例新辅助化疗前ER阳性转变为新辅助化疗后ER阴性,化疗前后患者ER表达变化有统计学差异(x~2=8.044,P=0.037);176例乳腺癌患者新辅助化疗前PR阳性为83例,新辅助化疗后PR阳性为89例,新辅助化疗前PR阴性为93例,新辅助化疗后PR阴性87例;新辅助化疗前后状态改变了82例(46.59%),其中45例新辅助化疗前PR阴性转变为PR阳性,37例新辅助化疗前PR阳性转变为新辅助化疗后PR阴性,化疗前后患者PR表达变化有统计学差异(x~2=6.311,P=0.049);176例乳腺癌患者新辅助化疗前HER2阳性为31例,新辅助化疗后HER2阳性为30例,新辅助化疗前HER2阴性为145例,新辅助化疗后HER2阴性146例;新辅助化疗前后状态改变了3例(1.70%),其中1例新辅助化疗前HER2阴性转变为HER2阳性,2例新辅助化疗前HER2阳性转变为新辅助化疗后HER2阴性,化疗前后患者HER2表达变化无统计学差异(x~2=0.522,P=0.945);176例乳腺癌患者新辅助化疗前Ki67阳性为104例,新辅助化疗后Ki67阳性为95例,新辅助化疗前Ki67阴性为72例,新辅助化疗后Ki67阴性81例;新辅助化疗前后状态改变了109例(61.93%),其中54例新辅助化疗前Ki67阴性转变为Ki67阳性,55例新辅助化疗前Ki67阳性转变为新辅助化疗后Ki67阴性,化疗前后患者Ki67表达变化有统计学差异(x~2=2.936,P=0.048),经过新辅助化疗后,Ki67出现上调表达最高,为23.86%,同时也是下调表达最高,为38.07%。HER2表达保持不变最高,为98.30%。结论:新辅助化疗会对乳腺癌患者ER、PR、Ki67的表达造成影响,其中对Ki67的影响最为显著。     

乳腺癌新辅助化疗疗效评价体系

目前新辅助化疗已广泛应用于乳腺癌的治疗,可降低肿瘤分期,提高手术切除率和增加保乳手术的机会。恰当的新辅助化疗疗效评价不仅可以指导患者治疗方案和预测预后,还可对不同药物的疗效提供可靠的评估。目前新辅助化疗评估主要采用临床检查如触诊、超声、钼靶X线、计算机断层显像、磁共振成像及病理学检查确定肿瘤体积变化,可分为临床评估和病理学评估。两者均有多种体系标准,未形成统一公认的标准。临床试验中采用较多的标准有WHO和RECIST等临床评价标准以及MP标准和JBCS标准等病理学评价标准。本文就乳腺癌新辅助化疗疗效评估体系进行总结。     

新辅助化疗配合手术治疗中晚期乳腺癌的临床效果分析

目的:观察新辅助化疗配合手术治疗中晚期乳腺癌的临床效果,为临床研究提供参考。方法:选取我院2009年5月-2011年4月收治的中晚期乳腺癌患者107例,根据治疗方法的不同,将患者分为新辅助化疗组和对照组。新辅助化疗组采取术前辅助化疗,而对照组术前不接受化疗。观察新辅助化疗组患者的近期临床疗效、毒副反应发生率;比较两组患者的手术时间、术中出血量等;术后随访三年,记录两组患者的肿瘤局部复发率及远处转移率。结果:新辅助化疗组患者治疗的总有效率为79.66%,毒副反应的发生率为33.89%;新辅助化疗组的平均手术时间、术中出血量均低于对照组,差异具有统计学意义(P0.05)。新辅助化疗组患者的局部复发率为5.08%,远处转移率为6.78%;对照组患者局部复发率为12.50%,远处转移率为18.75%。新辅助化疗组患者的肿瘤复发转移率低于对照组,差异具有统计学意义(P0.05)。结论:在中晚期乳腺癌的临床治疗中,术前对患者实施新辅助化疗具有明显的效果,患者近期疗效良好,毒副反应可耐受,且手术后的复发转移率相对较低,值得推广应用。     

探究新辅助化疗对胃癌细胞Bcl-2和p53基因表达的影响

胃癌在中国的发病率和死亡率居恶性肿瘤前列,现在胃癌的治疗主要以手术和化疗为主的综合治疗,新辅助化疗是胃癌综合治疗的重要组成部分,通过新辅助化疗能够有效抑制癌细胞增殖、缩小肿瘤体积等优点,从而为手术切除创造条件。本研究用新辅助化疗处理患胃癌的小鼠,并检测了新辅助化疗处理前后胃癌细胞内p53和Bcl-2 (细胞凋亡相关因子)基因在组织内的表达变化情况,以及与对照相比新辅助化疗对肿瘤大小的影响。结果表明,新辅助化疗可以减缓肿瘤的增长,显著上调小鼠胃癌组织内细胞凋亡因子p53的表达,并且显著下调Bcl-2抗凋亡因子的表达,从而有效地抑制胃癌细胞的增殖。这一结果可能为新辅助化疗对胃癌的治疗分子机制提供一些理论支持。     

NM-23、COX-2在胃腺癌FOLFOX新辅助化疗前后表达变化及其临床意义

目的:研究NM-23,COX-2在胃癌FOLFOX方案新辅助化疗前后的变化,探讨其作为新辅助化疗预测因子的可能性。方法:对95例局限进展期胃癌患者行FOLFOX-4方案新辅助化疗。新辅助化疗应用4个周期,共有85例患者完成新辅助化疗并接受了根治性或姑息性手术。免疫组织化学染色检测NM-23、COX-2的表达情况,并对比术前活检组织与术后切除标本中两种蛋白表达变化。结果:本组病例观察临床缓解率58.2%,疾病控制率90.1%。术前活检组织中NM-23阳性表达及COX-2阴性表达与化疗显效有关。新辅助化疗及术后,NM-23表达上升,COX-2表达下降。临床缓解组病例NM-23上升及COX-2下降均较临床未缓解病例显著(P<0.05)。结论:对FOLFOX新辅助化疗方案敏感的胃癌病例具有NM-23高表达、COX-2低表达的特点。此外,NM-23表达上调及COX-2表达降低可能与化疗显效有关。NM-23、COX-2可能作为新辅助化疗敏感人群的筛选指标和疗效判定指标。     

超声影像评效预测乳腺癌新辅助化疗病理评效的可行性研究

目的研究超声影像评效预测乳腺癌新辅助化疗病理评效的可行性。方法选取2013年6月~2016年6月在我院诊治的乳腺癌患者46例,所有入选患者均行新辅助化疗,术前采用超声测量残余病灶最大直径,研究与病理所得残余病灶最大直径的相关性,并以病理检查结果为金标准,分析超声检查对乳腺癌新辅助化疗后病理完全缓解的评估效果。结果超声测量残余病灶最大直径与病理评效结果呈正相关(r=0.960,P0.05);对浸润性癌残余病灶,超声诊断的敏感性为90.24%,特异性为40.00%,阳性预期值为92.50%,阴性预期值为33.33%。结论超声检查是评价乳腺癌新辅助化疗效果的有效检查方法,具有更广阔的应用前景。     

磁共振功能成像在监测乳腺癌新辅助化疗中的应用和进展

近年来,新辅助化疗在原发乳腺癌治疗中运用越来越广泛。影像学手段在评价新辅助化疗疗效、指导临床治疗方案的制定中发挥重要作用。磁共振功能成像的引入,可以加深对恶性乳腺肿瘤的病理生理活动及分子生物学特性的了解,监测化疗疗效,提高早期预测的准确性。本文总结功能学MRI(磁共振成像)探测乳腺癌患者生物标志物的研究现状及发展情况,描述各种生物学标志物特性,评价其潜在的临床应用价值和局限性。以下将对动态增强磁共振成像、弥散加权成像、血氧水平依赖成像以及波谱成像等几种磁共振功能学成像方法的原理进行描述,重点对其在监测乳腺癌新辅助化疗中的应用进行综述。     

NLR、PLR、LMR与乳腺癌新辅助化疗疗效及预后的关系研究

摘要 目的：探讨化疗前外周血中性粒细胞与淋巴细胞比值（NLR）、血小板与淋巴细胞比值（PLR）、淋巴细胞与单核细胞比值（LMR）与乳腺癌患者新辅助化疗疗效及预后的关系。方法：选择2016年10月至2018年1月在安徽医科大学附属安庆第一人民医院进行新辅助化疗的乳腺癌患者105例为研究对象,根据新辅助化疗疗效分为病理完全缓解（pCR）组（26例）和非pCR组（79例）。比较pCR组和非pCR组化疗前外周血NLR、PLR、LMR;采用受试者工作特征（ROC）曲线分析化疗前外周血NLR、PLR、LMR对乳腺癌患者新辅助化疗病理疗效预测价值。所有患者术后随访5年,根据ROC曲线确定的NLR、PLR、LMR最佳截断值分为高NLR、PLR、LMR组和低NLR、PLR、LMR组,采用K-M生存曲线分析不同NLR、PLR、LMR组5年无病生存期（DFS）;单因素和多因素COX回归分析预后不良的影响因素。结果：pCR组化疗前NLR、PLR均低于非pCR组（P＜0.05）,LMR高于非pCR组（P＜0.05）。化疗前NLR、PLR、LMR三项联合预测新辅助化疗病理疗效的曲线下面积（AUC）均大于各指标单独预测。K-M生存曲线分析显示,化疗前高NLR、PLR组5年DFS分别低于低NLR、PLR组（P＜0.05）,高LMR组5年DFS高于低LMR组（P＜0.05）;多因素COX回归分析显示,NLR、PLR升高是乳腺癌预后的危险因素,LMR升高是保护因素（P<0.05）。结论：pCR组化疗前NLR、PLR更低,LMR更高,高NLR、PLR和低LMR患者5年DFS更低。NLR、PLR、LMR对新辅助化疗病理疗效具有一定的预测价值,三项联合能为乳腺癌的新辅助化疗评估提供重要参考依据。     

乳腺癌化疗现状及相关研究进展

乳腺癌是除非上皮来源肿瘤中女性最常见的恶性肿瘤,在美国平均每3名女性中就有一名患乳腺癌,是女性肿瘤致死中的第二大原因,给政府经济造成了很大的损失。目前,乳腺癌主要是以手术治疗为主,而化疗,放疗等也作为相当重要的辅助治疗应用于临床。这种手术加化疗的治疗方法一直可以取得很好的疗效,甚至于可以保住乳房。近年来,乳腺癌的化疗已逐步成为其治疗的首选方式,包括术后辅助化疗和术前的新辅助化疗。但由于化疗药物的滥用和肿瘤本身的异质性或是其他原因,越来越多的肿瘤耐药性报道给乳腺癌的化疗带来了很大的挑战。而这种肿瘤耐药性的分子机制尚不是很清楚。本文将从乳腺癌的概述,乳腺癌化疗的现状及乳腺癌化疗的前景来综述这一灾难性疾病。     

Correlation analysis of lymphocyte-monocyte ratio with pathological complete response and clinical prognosis of neoadjuvant chemotherapy in patients with breast cancer

PurposeInflammation plays an important role in tumor proliferation, metastasis, and chemotherapy resistance. Peripheral blood lymphocyte-monocyte ratio (LMR) has been reported to be closely associated with the prognosis of many tumors, such as certain hematologic malignancies and gastric cancer. However, the association in breast cancer is still not clear. This study investigated the relationship between LMR with pathological complete response and clinical prognosis of neoadjuvant chemotherapy in patients with breast cancer, to provide convenient and accurate predictive indicators for pathological complete response (pCR) and prognosis.MethodsThe clinicopathological data of 192 female breast cancer patients who received neoadjuvant chemotherapy and surgery in Harbin Medical University Tumor Hospital from January 2013 to August 2017 were retrospectively analyzed. Blood lymphocytes and monocytes were obtained by peripheral venous punctures.ResultsCompared with the low LMR group, pCR was more easily obtained in the high LMR group (P=0.020); Subgroup analysis showed that patients with the high LMR and HER-2(+) group were more likely to obtain pCR (P=0.011).Univariate andmultivariate results showed that the overall survival (OS) and disease free survival (DFS) of the high LMR group were longer than that of the low LMR group.ConclusionLMR and HER-2 status are correlated with pCR of neoadjuvant chemotherapy in breast cancer patients and are independent predictors of pCR after neoadjuvant chemotherapy in breast cancer patients. Meanwhile, both LMR and T stage of tumor are independent prognostic factors of breast cancer patients, with good predictive value.     

Late chronotypes are associated with neoadjuvant chemotherapy-induced nausea and vomiting in women with breast cancer

Neoadjuvant chemotherapy, that is, the administration of chemotherapy before surgery, has been commonly used for locally advanced breast cancer to improve the surgical outcomes and increase the opportunity for breast-conserving therapy. Women with breast cancer often receive an anthracycline-based regimen as the neoadjuvant chemotherapy, which is associated with a high risk of emesis. Despite the development of novel antiemetics, chemotherapy-induced nausea and vomiting (CINV) has been commonly reported as a major adverse effect, affecting the quality of life of the patients. However, the factors predicting CINV in women with breast cancer undergoing neoadjuvant chemotherapy remain unclear. In this single-institution, prospective, observational study conducted at an outpatient cancer centre in the Republic of Korea from November 2013 to March 2016, we analysed women with breast cancer who planned to be treated with neoadjuvant chemotherapy before surgery. Candidate factors associated with CINV were assessed before neoadjuvant chemotherapy using the Munich Chronotype Questionnaire, Pittsburgh Sleep Quality Index and Hospital Anxiety and Depression Scale. CINV was assessed after chemotherapy by using the Multinational Association of Supportive Care in Cancer Antiemesis Tool. Of a total of 143 participants, 7 patients were lost to follow-up and 2 patients were excluded due to changes in their treatment plan; thus, 134 patients were finally included in the analyses. Overall, 48.5% of the participants experienced CINV, with delayed CINV prevalence (42.5%) being more common than acute (39.6%). In the univariate analyses, overall CINV was significantly associated with late chronotypes (odds ratio [OR], 3.49; 95% confidence interval [CI], 1.37–8.87; p = 0.009), a history of nausea/vomiting (OR, 2.19; 95% CI, 1.10–4.37; p = 0.026) and anxiety (OR, 2.25; 95% CI, 1.05–4.81; p = 0.036). In the multivariate analyses, late chronotypes (OR, 3.53; 95% CI, 1.27–9.79; p = 0.015) and a history of nausea/vomiting (OR, 2.83; 95% CI, 1.31–6.13; p = 0.008) remained significantly associated with CINV. In conclusion, in women with breast cancer undergoing neoadjuvant chemotherapy before surgery, late chronotypes were found to have an increased risk of CINV; these data suggest that clinicians need to assess and consider the chronotype in the management of CINV.     

Clinical Efficacy of Including Capecitabine in Neoadjuvant Chemotherapy for Breast Cancer: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background

Capecitabine has proven effective as a chemotherapy for metastatic breast cancer. Though several Phase II/III studies of capecitabine as neoadjuvant chemotherapy have been conducted, the results still remain inconsistent. Therefore, we performed a meta-analysis to obtain more precise understanding of the role of capecitabine in neoadjuvant chemotherapy for breast cancer patients.

Methods

The electronic database PubMed and online abstracts from ASCO and SABCS were searched to identify randomized clinical trials comparing neoadjuvant chemotherapy with or without capecitabine in early/operable breast cancer patients without distant metastasis. Risk ratios were used to estimate the association between capecitabine in neoadjuvant chemotherapy and various efficacy outcomes. Fixed- or random-effect models were adopted to pool data in RevMan 5.1.

Results

Five studies were included in the meta-analysis. Neoadjuvant use of capecitabine with anthracycline and/or taxane based therapy was not associated with significant improvement in clinical outcomes including: pathologic complete response in breast (pCR; RR = 1.10, 95% CI 0.87–1.40, p = 0.43), pCR in breast tumor and nodes (tnpCR RR = 0.99, 95% CI 0.83–1.18, p = 0.90), overall response rate (ORR; RR = 1.00, 95% CI 0.94–1.07, p = 0.93), or breast-conserving surgery (BCS; RR = 0.98, 95% CI 0.93–1.04, p = 0.49).

Conclusions

Neoadjuvant treatment of breast cancer involving capecitabine did not significantly improve pCR, tnpCR, BCS or ORR. Thus adding capecitabine to neoadjuvant chemotherapy regimes is unlikely to improve outcomes in breast cancer patients without distant metastasis. Further research is required to establish the condition that capecitabine may be useful in breast cancer neoadjuvant chemotherapy.     

初诊腋窝淋巴结阳性乳腺癌新辅助化疗后对腋窝淋巴结转阴性前哨活检的影响分析

摘要 目的：探究对初诊腋窝淋巴结阳性乳腺癌行新辅助化疗患者开展腋窝前哨淋巴结活检的临床意义。方法：选择2017年1月至2020年10月于我院接受改良根治术或保乳术治疗的100例初诊腋窝淋巴结阳性乳腺癌患者,将其中50例病理检测II B、III期行4~8个疗程新辅助化疗后实施前哨淋巴结活检患者设为研究组,将50例I、II A期直接行前哨淋巴结活检患者设为对照组,对比两组患者前哨淋巴结检出率、准确率、假阴性率和灵敏度,同时就患者病理特征与前哨淋巴结检出率的相关性开展分析。结果：（1）比较显示研究组患者与对照组患者在前哨淋巴结检出数、前哨淋巴结检出率以及前哨淋巴结假阴性率方面组间差异不大（P>0.05）;（2）病理学特征分析显示肿瘤直径以及临床N分期同新辅助化疗后患者前哨淋巴结检出阳性率密切相关（P<0.05）。结论：对初诊腋窝淋巴结阳性行新辅助化疗乳腺癌患者实施前哨淋巴结活检具有较显示的临床意义,能够较好的预测患者腋窝淋巴结状况,同时化疗前肿瘤直径、临床N分期是影响前哨淋巴结检出率的重要影响因素。     

彩色多普勒超声对乳腺癌新辅助化疗疗效的评价研究

目的:探讨彩色多普勒超声(CDFI)对乳腺癌新辅助化疗(NCT)疗效评价的临床应用价值。方法:选取2013年1月~2013年12月在我院接受新辅助化疗后行手术治疗的女性乳腺癌患者55例,以病理学评价为金标准,化疗后根据化疗效果分为有效组和无效组,利用CDFI观察患者NCT前后病灶超声指标、病灶内血流分级及阻力指数(RI)值变化。结果:55例患者中,临床触诊疗效评价符合率为36.4%,敏感度为60.7%;CDFI评价符合率为70.9%,敏感度为85.7%。CDFI检查显示,乳腺癌NCT后原发肿瘤病灶大小显著缩小,边界多清晰可见,内部回声及后方回声倾向正常。有效组NCT前后病灶内的血流类型和RI值变化有统计学意义(P0.05),无效组NCT前后病灶内的血流类型和RI值无明显变化(P0.05)。结论:CDFI技术可对乳腺癌NCT前后病灶大小及病灶内部血流动力学变化提供客观参数,是评价乳腺癌NCT疗效的有效方法。     

Pre-treatment systemic immune-inflammation index is a useful prognostic indicator in patients with breast cancer undergoing neoadjuvant chemotherapy

The systemic immune-inflammation index (SII = N × P/L) based on neutrophil (N), platelet (P) and lymphocyte (L) counts is used to predict the survival of patients with malignant tumours and can fully reflect the balance between host inflammatory and immune status. This study is conducted to explore the potential prognostic significance of SII in patients with breast cancer undergoing neoadjuvant chemotherapy (NACT). A total of 262 patients with breast cancer received NACT were enrolled in this study. According to the receiver operating characteristic curve, the optimal cut-off value of SII was divided into two groups: low SII group (<602 × 10⁹/L) and high SII group (≥602 × 10⁹/L). The associations between breast cancer and clinicopathological variables by SII were determined by chi-squared test or Fisher's exact test. The Kaplan-Meier plots and log-rank test were used to determine clinical outcomes of disease-free survival (DFS) and overall survival (OS). The prognostic value of SII was analysed by univariate and multivariate Cox proportional hazards regression models. The toxicity of NACT was accessed by National Cancer Institute Common Toxicity Criteria (NCICTC). According to univariate and multivariate Cox regression survival analyses, the results showed that the value of SII had prognostic significance for DFS and OS. The patients with low SII value had longer DFS and OS than those with high SII value (31.11 vs 40.76 months, HR: 1.075, 95% CI: 0.718-1.610, P = .006; 44.47 vs 53.68 months, HR: 1.051, 95% CI: 0.707-1.564, P = .005, respectively). The incidence of DFS and OS in breast cancer patients with low SII value was higher than that in those patients with high SII value in 3-, 5- and 10-year rates. The common toxicities after NACT were haematological and gastrointestinal reaction, and there were no differences by SII for the assessment of side effects of neoadjuvant chemotherapy. Meanwhile, the results also proved that breast cancer patients with low SII value and high Miller and Payne grade (MPG) survived longer than those breast cancer with high SII value and low MPG grade. In patients without lymph vessel invasion, these breast cancer patients with low SII value had better prognosis and lower recurrence rates than those with high SII value. Pre-treatment SII with the advantage of reproducible, convenient and non-invasive was a useful prognostic indicator for breast cancer patients undergoing neoadjuvant chemotherapy and is a promising biomarker for breast cancer on treatment strategy decisions.     

新辅助化疗后腋窝病理完全缓解乳腺癌的预后分析

摘要 目的：研究乳腺癌患者新辅助化疗（NAC）后达到腋窝淋巴结病理完全缓解（pathologic complete response of axillary,apCR）的远期生存以及影响远期生存的相关因素分析。方法：回顾性分析哈尔滨医科大学附属肿瘤医院乳腺外科624例乳腺癌患者的住院资料,采用Kaplan-Meier生存分析以及COX回归分析的统计学分析方法,分析乳腺癌患者新辅助化疗后腋窝状态与无病生存（DFS）和总生存（OS）的关系及影响apCR预后的因素。结果：apCR与非apCR患者比较DFS（P=0.013）和OS（P=0.037）差异具有统计学意义,apCR患者的预后与年龄、肿瘤大小、肿瘤受体状态、HER-2、ki67状态、分子分型等因素无相关性。结论：与非apCR患者相比,乳腺癌患者新辅助化疗后apCR患者预后更好,但apCR患者预后良好的因素仍需进一步临床试验分析。