乳腺癌宽芯针穿刺活检与术后病理一致性及对新辅助化疗影响的研究

发布时间：2018-06-17 13:40

本文选题：乳腺癌 + 空芯针活组织检查　；参考：《中国人民解放军军事医学科学院》2016年硕士论文

【摘要】：目的乳腺癌在我国近十几年总体发病率呈现上升趋势,位居城乡女性首位,是危害生命健康的最主要的恶性肿瘤之一。1980年Fisher医生提出乳腺癌是一个全身性疾病的新生物学观点。随着对乳腺癌研究的不断深入,Fisher的观点被越来越广泛的接受。目前根据2015年NCCN指南,中晚期乳腺癌推荐行新辅助化疗(neoadjuvant chemotherapy,NAC),新辅助化疗可提高乳腺手术的保乳率,使越来越多的患者避免切除乳房的困扰,已逐渐成为诊疗常规。新辅助化疗方案选择和制定必须依据空芯针穿刺活检所取得的肿瘤组织病理及免疫组化结果,在不能获得全部肿瘤组织的情况下,空芯针穿刺病理的准确性就显得十分重要,虽然已有文献证实空芯针穿刺病理的准确性,但是在临床诊治过程中,乳腺癌穿刺活检与术后病理之间,病理类型和免疫组化结果存在一定的不一致,文献报道雌激素受体(estrogen receptor,ER)、孕激素受体(progesterone receptor,PR)、表皮生长因子受体2(human epidermal growthfactor receptor 2,HER2)受体的不一致比例3%-18%不等。受体状态的变化是否会对患者新辅助的治疗效果产生影响少有文献报道。本项研究应用大样本量的回顾性分析对穿刺活检和术后病理、新辅助治疗前后的病理和免疫组化的一致性进行研究,并分析病理和免疫组化的一致性对新辅助化疗的影响。探索肿瘤穿刺后和新辅助化疗后病理、ER、PR、HER2受体和Ki67值的变化规律,给临床治疗提供一些有效的指导,给术后辅助化疗提供一些参考的依据。材料与方法选取统计军事医学科学院附属医院从2011年11月到2015年6月行乳腺肿物穿刺活检的乳腺癌病例,患者在穿刺前未行任何与肿瘤相关的治疗,根据病人穿刺后行手术还是新辅助化疗,将病人分为穿刺-手术组和穿刺-化疗-手术组两组。共收集穿刺-手术组病例205例,穿刺-化疗-手术组病例439例。第一部分：穿刺-手术组病例的病理一致性分析1.配对同一名患者的穿刺活检与术后病理标本。补充和完善穿刺-手术组病例的临床信息及穿刺活检与术后的病理及免疫组化(ER、PR、HER2、Ki67)结果。205例患者中有2例穿刺没有诊断而术后病理确诊恶性,有5例为不典型、3例不能排除恶性建议均建议手术确诊。共有188例病例穿刺与手术标本均诊断为乳腺癌并有完善的病理资料。2.病理医生复核病理及免疫组化结果。3.Ki67以14%为界,≤14%为低表达,14%为高表达。对ER、PR、HER2、Ki67和分子分型共5个项目进行一致性检验,计算一致率并记录其变化(如ER的上调或下降等)。第二部分：穿刺-化疗-手术组的病理一致性分析1.配对同一名患者的新辅助治疗前后的病理标本。补充和完善穿刺-化疗-手术组病例的临床信息及新辅助化疗前后病理及免疫组化(ER、PR、HER2、Ki67)结果,439例中行蒽环类联合紫衫类(AT)方案205例,蒽环类联合紫衫类序贯长春瑞宾联合顺铂(AT-NP)方案54例,蒽环类联合紫衫类加曲妥珠单抗(ATH)方案62例,多西他赛联合卡铂加曲妥珠单抗(TCH)方案12例,多西他赛联合联合卡培他滨(TX)方案4例,其他方案102例。行AT方案205个病例中,共有165例病例有完善的病理资料,病理完全缓解(pathologic complete response,PCR)28例。2.病理医生复核病理及免疫组化结果。3.Ki67以14%为界, 茎14%为低表达,14%为高表达。对ER、PR、HER2、KI67和分子分型共5个项目进行一致性检验,计算一致率并记录其变化(如ER的上调或下降等)。第三部分：判断ER、PR、HER2受体状态的变化对新辅助化疗疗效的影响。1.根据穿刺-化疗-手术组病例穿刺活检与术后的病理及免疫组化中ER、PR、HER2的表达是否相同,有一个项目不同为不一致,将穿刺-化疗-手术组病例分为一致组和不一致组两组。2.统计两组患者NAC后肿瘤的缓解率。缓解率=[(治疗前最大径-治疗后最大径)/治疗前最大径]×100%。3.使用t检验统计分析两组病人的缓解率是否存在差异。所有数据均使用SAS9.1版软件进行统计分析,以P0.05有统计学意义。结果1.穿刺活检诊断乳腺癌的敏感度和特异度分别99.02%和95.12%。穿刺-手术组的188例乳腺癌患者CNB和OEB标本的病理类型一致,P=0.9955,分子亚型时一致率为72.34%,k=0.6064。ER,PR,HER2的一致率分别为94.68%,k=0.862、93.62%,k=0.8658和94.68%,k=0.8539,一致率均在93%以上,kappa检验的结果k值均大于0.75,显示具有很好的一致性。开放切除活检(open excision biopsy,OEB)样本中Ki67的表达高于CNB样本,一致率为73.40%,k=0.1492,提示一致性差,两者的平均数分别为21.649%和25.899%,对两组Ki67值进行了配对设计定量资料的符号秩和检验,结果S=617,P=0.0013,差异具有统计学意义。2.穿刺-化疗-手术组中行AT新辅助治疗的137名患者的治疗前后乳腺癌分子分型的一致率为56.64%,k=0.3778。ER、PR、HER2的一致率分别为87.61%,k=0.6678、80.53%,k=0.5959和93.81%,k=0.4305。Kappa值位于0.45-0.75之间,只有较好的一致性。对比穿刺-手术组的一致性检验结果,NAC对ER、PR、HER2的一致性存在影响。其中ER、HER2受体的阳性率无明显变化,PR受体更易受到化疗的影响导致阳性率下降。HR受体的状态没有受到NAC的影响,一致率为92.7%,k=0.796。Ki67的表达在NAC后明显降低(P0.001),平均数分别是35.75%和19.12%。137例患者中有44例出现了ER、PR、HER2的受体状态的改变,占总例数的32.11%。根据AT新辅助化疗的周期数将病例分为4周期组,6周期组和8周期组,则ER、PR、HER2的受体状态的改变率分别为27.08%,39.22%,38.46%。3.根据新辅助化疗前后ER、PR、HER2的受体状态是否一致,将137个病人分为一致组和差异组。计算两组患者的肿瘤临床缓解率(clinical response rate,cRR),均数分别为48.51%和48.20%,P=0.0957,差异没有统计学意义。结论1.CNB可以准确确定乳腺癌的ER、PR和HER2状态以及Ki67值。对于non-Luminal型的肿瘤,术前CNB即可准确确定分子亚型。对于性激素受体(HR)+/HER2-标本,由于CNB后Ki67值会上升,在制定NAC方案时应考虑此因素。2.NAC会使乳腺癌Ki67的表达下降,并在一定程度上引起雌激素受体(ER)、孕激素受体(PR)、HER2的表达下调,但差异均没有统计学意义,也不会对HR受体产生影响。3. ER、PR、HER2的改变率与NAC的周期数成正比,在6周期后达到高峰。4. ER、PR、HER2受体状态的变化并不会引起NAC疗效上的差异。CNB可作为选择NAC方案的可靠依据。
[Abstract]:Objective the overall incidence of breast cancer in China has increased in the past decade, ranking first in urban and rural women. It is one of the most important malignant tumors that endanger life and health. Dr. Fisher proposed that breast cancer is a new biological view of a systemic disease in.1980. With the deepening of research on breast cancer, the view of Fisher is becoming more and more important. Widely accepted. According to the 2015 NCCN guide, new adjuvant chemotherapy (neoadjuvant chemotherapy, NAC) is recommended for middle and late stage breast cancer. Neoadjuvant chemotherapy can improve breast conserving rate of breast surgery and make more and more patients avoid the problem of breast resection. The results of histopathology and immunohistochemistry obtained by needle aspiration biopsy are very important for the accuracy of the pathology of the puncture needle puncture, although the accuracy of hollow needle puncture pathology has been proved in the literature, but during the clinical diagnosis, the biopsy of the breast cancer and the postoperative pathology There was a certain disagreement between the pathological and immunohistochemical results. The literature reported that the estrogen receptor (estrogen receptor, ER), progestin receptor (progesterone receptor, PR), epidermal growth factor receptor 2 (human epidermal growthfactor receptor 2, HER2) were different proportions of 3%-18%. The effect of new adjuvant therapy was rarely reported. This study used a retrospective analysis of a large sample of biopsy and postoperative pathology, the consistency of pathology and immunohistochemistry before and after neoadjuvant therapy, and analyzed the effect of the consistency of pathology and immunohistochemistry on neoadjuvant chemotherapy. And the changes of ER, PR, HER2 receptor and Ki67 value after neoadjuvant chemotherapy, provide some effective guidance for clinical treatment, provide some reference basis for postoperative adjuvant chemotherapy. Materials and methods selected statistics of breast cancer cases from November 2011 to June 2015 of the Affiliated Hospital of Military Medical Science Academy of the PLA, The patient was not treated with any tumor related treatment before the puncture. According to the patient's puncture operation or neoadjuvant chemotherapy, the patients were divided into two groups: puncture operation group and puncture chemotherapy operation group. A total of 205 cases of puncture operation group, 439 cases of puncture chemotherapy operation group were collected. Part 1: pathological agreement in the puncture operation group. Paracentesis and postoperative pathological specimens of 1. matched patients. Supplementary and perfected the clinical information of the cases of the puncture and operation group and the results of biopsy and postoperative pathology and immunohistochemistry (ER, PR, HER2, Ki67). There were 2 cases in.205 patients without diagnosis but 5 cases were atypical, 3 cases were not excluded. A total of 188 cases were diagnosed as breast cancer and 188 cases were diagnosed as breast cancer and had perfect pathological data. The pathological and pathological findings of the pathology and immunohistochemical results were 14%, low expression of less than 14%, and high expression of 14%. A total of 5 items of ER, PR, HER2, Ki67 and molecular typing were tested and calculated. The rate of consistency and records of changes (such as the up or down of ER). The second part: the pathological consistency analysis of the puncture, chemotherapy and operation group. 1. pairs of the pathological specimens of the same patient before and after the new adjuvant treatment. Supplement and improve the clinical information of the case of the puncture chemotherapy operation group and the pathological and immunohistochemical (ER, PR, HER2, Ki) before and after the neoadjuvant chemotherapy 67) 439 cases, 205 cases of anthracycline combined purple shirt (AT), 54 cases of anthracene ring combined with Changchun ribin combined with cisplatin (AT-NP), 62 cases of anthracycline combined with ATH, 12 cases of docetaxel combined with carboplatin plus trumpet (TCH), docetaxel combined with capecitabine (TX). Of the 4 cases and other 102 cases, of the 205 cases of AT scheme, 165 cases had perfect pathological data, pathological complete remission (pathologic complete response, PCR) 28 cases of.2. pathologists, pathological and immunohistochemical results,.3.Ki67 to 14%, low expression of stem 14%, and 14% high expression. ER, PR, HER2, KI67, and molecular typing were 5. The third part: determine the effect of ER, PR, HER2 receptor status on the effect of neoadjuvant chemotherapy..1. based on the same expression of ER, PR, HER2 in the biopsy and postoperative pathology and immunohistochemistry of the puncture chemotherapy operation group, and the same, there is one of the same. Different items were different, the cases of puncture chemotherapy and operation group were divided into two groups of unanimous group and unconforming group. Two groups of.2. statistics in two groups of patients were remission rate after NAC. The remission rate = [(the maximum diameter before treatment - the maximum diameter after treatment) / the maximum diameter before treatment] x 100%.3. by t test statistics analysis of the remission rates of two groups of patients. According to the statistical analysis of SAS9.1 software, the results of P0.05 were statistically significant. Results 1. the sensitivity and specificity of breast cancer diagnosis were 99.02% and 95.12%., respectively, and 188 cases of breast cancer patients with breast cancer were consistent with the pathological types of CNB and OEB, P=0.9955, the consistency rate of the molecular subtypes was 72.34%, k=0.6064.ER, PR, HER2. The rates were 94.68%, k=0.862,93.62%, k=0.8658, and 94.68%, and k=0.8539, all the conformance rates were above 93%. The k values of kappa test were all greater than 0.75, showing a good consistency. The expression of Ki67 in the samples of open excision biopsy (open excision biopsy, OEB) was higher than that of CNB sample, and the consensus rate was 73.40%. K=0.1492, suggesting that the consistency was poor, both were flat. The average numbers were 21.649% and 25.899% respectively. The symbol rank and test of the paired design quantitative data were carried out for the Ki67 values of the two groups. The results were S=617, P=0.0013, and the difference was statistically significant in 137 patients with AT neoadjuvant therapy in the.2. puncture chemotherapy operation group. The consistency of the molecular classification of breast cancer before and after treatment was 56.64%, k=0.3778.ER, PR, HER2. The rates were 87.61%, k=0.6678,80.53%, k=0.5959 and 93.81%, and the k=0.4305.Kappa value was between 0.45-0.75, only good consistency. Compared with the consistency test of the puncture operation group, NAC had an effect on the consistency of ER, PR, HER2. The positive rate of ER, HER2 receptor was not obviously changed, and PR receptor was more susceptible to the effect of chemotherapy. The state of.HR receptor was not affected by NAC, the consistency rate was 92.7%, the expression of k=0.796.Ki67 decreased significantly after NAC (P0.001). The average number of 35.75% and 19.12%.137 patients had 44 cases of ER, PR, and HER2 receptor state changes, and the 32.11%. of the total number of cases divided the cases into 4 according to the cycle number of AT neoadjuvant chemotherapy. In the periodic group, the 6 cycle group and the 8 cycle group, the changes of the receptor status of ER, PR, and HER2 were 27.08%, 39.22%, and 38.46%.3. were based on the consistent receptor status of ER, PR and HER2 before and after the neoadjuvant chemotherapy. The 137 patients were divided into the same group and the difference group. The clinical remission rate (clinical response rate, cRR) of the two groups of patients was calculated, respectively. For 48.51% and 48.20%, P=0.0957, the difference is not statistically significant. Conclusion 1.CNB can accurately determine the ER, PR and HER2 status of breast cancer and the Ki67 value. For the non-Luminal type tumor, the preoperative CNB can accurately determine the molecular subtype. For the sex hormone receptor (HR) +/HER2- specimens, the Ki67 value will rise after CNB, and should be considered in the formulation of the scheme. This factor.2.NAC can decrease the expression of Ki67 in breast cancer, and to some extent cause the estrogen receptor (ER), progesterone receptor (PR) and HER2 expression down, but the difference is not statistically significant, and does not affect the HR receptor of.3. ER, PR, HER2 is proportional to the cycle number of NAC, reaching the peak after the 6 cycle. Changes in body status will not cause differences in the efficacy of NAC..CNB can be used as a reliable basis for selecting NAC protocols.
【学位授予单位】：中国人民解放军军事医学科学院
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R737.9

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