乳腺癌新辅助化疗疗效及其预后影响因素的分析

发布时间：2018-05-27 06:17

本文选题：乳腺癌 + 新辅助化疗　；参考：《山东大学》2017年硕士论文

【摘要】：目的近年来,我国的女性乳癌发病率迅猛上升,现已严重威胁着患病者的生命健康。乳腺癌治疗的方式也从传统的单纯手术转化为以手术方式为主的综合治疗,因此,新辅助化疗应运而生,并且已发展成为各阶段乳腺癌治疗的一种选择,它的应用使得众多不可手术的乳腺癌患者获得手术机会、甚至是保乳机会,并且达到了改善预后、延长生存的目的。但是仍然留有20%的患者不能获益于新辅助化疗。因此,发展一种可靠的、个体化的新辅助化疗方案,以提高乳腺癌患者的生存质量以及改善其预后显得尤为重要。方法搜集2010年1月到2016年8月收治于山东大学齐鲁医院乳腺外科的女性乳腺癌NAC患者的相关临床、病理资料,对其展开回顾性分析。收集的信息主要包括:患者年龄、婚育史、哺乳情况、身高体重(BMI)、初诊时及新辅助化疗后的临床查体情况(包括肿块的大小、位置、距乳晕距离以及乳房伴随表现、淋巴结的状态等)、初诊时及NAC后的的影像学表现(包括彩超、钼靶)及实验室检查结果、新辅助化疗前后的病理学诊断(肿瘤类型、组织学分级、免疫组化指标等)、淋巴结状态、以及进行的NAC方案、周期、剂量,患者接受的手术方式,通过随访电话得到患者后续的化疗、放疗、内分泌治疗状态,化疗期间副反应,以及术后转移、复发和生存状况。治疗前的临床分期参考UICC的TNM分期之乳腺癌标准;临床评估参照国际抗癌协会制订公布的实体肿瘤疗效评价方法,即Resistl标准;病理学评估参照Miller Payne(MP)病理评价方法;使用Luminal分型对NAC患者进行分子亚型的划分。应用SPSS 23.0软件对收集的数据进行统计学处理:采用卡方检验分析分类变量与NAC疗效的关系;采用T检验来分析连续性变量与NAC疗效的关系;采用配对检验(卡方或T检验)分析化疗前后临床生物学及病理学指标的改变;应用多元Logistic回归来分析单因素分析存在统计学意义的因素;采用Kaplan-Meier法及C0X回归来分析不同临床病理学指标影响患者预后的作用大小。以P0.05为差异具有统计学意义。结果1.研究纳入343名乳腺癌新辅助化疗患者,化疗结束后均行手术治疗,术后病理28人达到MP5级,pCR率10.4%。截止至随访结束,共随访到患者313人,随访率 91.3%。2.疗效影响因素分析:以pCR作为疗效评价指标时,不伴有乳头凹陷(P=0.008),钼靶无钙化灶(P=0.009),NAC 后查体无明显肿块(P0.001),非 Luminal 型(P=0.044),PR阴性者(P=0.028)的pCR率较高,且差异有统计学意义。三阴性者的pCR率高于其他类型,且与LuminalB型之间的差异具有统计学意义(P=0.008)。以病理大部缓解作为疗效评价指标时,分娩次数≤1次(P=0.028),NAC后查体无明显肿块(P0.001),NAC前Ki67高表达者(P=0.039)的病理大部缓解率较高,且差异有统计学意义。NAC前T彩超分期(P=0.028)、Luminal分型(P=0.037)、组织学分级(P=0.022)、化疗周期数(P=0.022)与病理大部缓解之间均具有显著相关性。二元Logistic回归分析可见,NAC后查体是否有明显肿块(P=0.012)及NAC前是否有乳头凹陷(P=0.026)可作为pCR的独立预测因子;组织学分级(P=0.024)、NAC后查体是否有明显肿块(P=0.032)可以作为病理大部缓解的独立预测因子;化疗方案(P=0.005)及化疗周期总数(P0.001)可以作为临床缓解的独立预测因子。3.化疗用药对疗效的影响:在ET方案新辅助化疗中,完成≥6个周期者具有更高的病理大部缓解率(27..5%VS 8.8%,P=0.004)、CR 率(17.5%VS 3.4%,P=0.044)和临床缓解率(80.0%VS 50.0%,P=0.003);较高的化疗剂量强度提示更好的疗效,但差异不具有统计学意义。4.齐鲁医院临床医生用药习惯研究:近7年来,NAC以ET方案为主(46.6%),CEF方案应用比例逐年减少,TEC方案应用比例逐年提高,且不同年份、NAC方案所占比例之间具有显著性差异(P0.001)。分析影响临床医生选择NAC方案的因素,可见治疗的年份、患者年龄、初诊时查体是否有乳头溢液、分子分型是否为Luminal型、组织学分级、NAC前ER和PR的状态都对临床医生选择化疗方案造成显著性影响。但仅有治疗年份和患者的年龄是指导临床医生选择化疗方案的独立影响因子(P=0.013、P=0.004)。5.预后影响因素分析:不同的复发转移部位(P=0.003)、NAC期间是否出现骨髓抑制(P=0.013)、术后放疗情况(P0.001)、术后患肢淋巴水肿的情况(P=0.048)、是否达到病理大部缓解(P=0.044)、是否达到pCR(P=0.005)、NAC后是否属于Luminal型(P=0.004)、NAC前T彩超分期(P0.001)、T查体分期(P0.001)以及术后转移LN/检出LN值(P=0.001)均与患者的生存率显著相关。纳入COX回归,可看出手术病理查见转移LN占检出LN的比例是否大于30%(P=0.003)、是否为Luminal型(P=0.002)、是否达到病理大部缓解(P=0.02)均可以作为影响乳腺癌NAC患者生存期的独立因子。结论1.NAC后查体是否可触及肿块为pCR的独立预测因子;组织学分级、NAC后是否可触及肿块为病理大部缓解的独立预测因子;NAC方案及周期数为临床缓解的独立影响因子。2.化疗方案的选择影响化疗效果,且足量足疗程的化疗提示更好的效果。3.临床医生有待进一步强化NAC个体化意识,使患者更多的受益于化疗。4.术后病理转移LN/检出LN是否大于30%(P=0.003)、是否为Luminal型(P=0.002)、是否达到病理大部缓解(P=0.02)可以作为影响乳腺癌NAC患者生存期的独立因子。
[Abstract]:Objective in recent years, the incidence of female breast cancer in China has been rising rapidly, and it is now a serious threat to the health of the patients. The treatment of breast cancer has been transformed from a traditional simple operation into a comprehensive treatment based on the operation mode. Therefore, the neoadjuvant chemotherapy has emerged as the times require, and has developed into a choice for the treatment of breast cancer at all stages. Its application makes many non operable breast cancer patients get surgical opportunities, even breast conserving opportunities, and improve the prognosis and prolong survival. But 20% of the patients still remain unable to benefit from neoadjuvant chemotherapy. Therefore, a reliable, individualized new adjuvant chemotherapy scheme is developed to improve the birth of breast cancer patients. The survival quality and the improvement of the prognosis are particularly important. Methods the clinical and pathological data were collected from January 2010 to August 2016 in women with breast cancer NAC in Qilu Hospital of Qilu Hospital of Shandong University. The information mainly included age, history of marriage and childbirth, breast feeding, and height and weight (BMI). The clinical manifestations of primary and neoadjuvant chemotherapy (including the size of the mass, location, distance from the areola and the breast, the status of the lymph nodes, etc.), the imaging findings of first diagnosis and after NAC (including color Doppler ultrasound, molybdenum target) and laboratory examination, and the pathological diagnosis (tumor type, histological grading, and histology) before and after adjuvant chemotherapy. Immuno histochemical index, lymph node status, and NAC regimen, cycle, dose, patient's surgical approach, follow-up telephone calls to receive follow-up chemotherapy, radiotherapy, endocrine therapy, side effects during chemotherapy, and postoperative metastasis, recurrence, and survival. TNM staging of UICC before treatment Cancer standards; the clinical evaluation referred to the international anticancer association, which was published by the international anticancer association, that is, the Resistl standard; the pathological evaluation referred to the Miller Payne (MP) pathological evaluation method; the Luminal classification was used to divide the molecular subtypes of the NAC patients. The data collected by SPSS 23 soft ware were statistically processed: using chi square The relationship between the classification variables and the curative effect of NAC was tested and analyzed; the relationship between the continuous variables and the curative effect of NAC was analyzed by T test; the changes of clinical biological and pathological indexes before and after chemotherapy were analyzed by paired test (chi square or T test); the multivariate Logistic return was used to analyze the factors of statistical significance in the analysis of monicin; and Kaplan-Mei The ER method and C0X return analysis were used to analyze the effect of different clinical and pathological indexes on the prognosis of the patients. The difference of P0.05 was statistically significant. Results 1. studies were included in 343 neoadjuvant chemotherapy patients with breast cancer. After chemotherapy, all the patients were treated with surgical treatment. The postoperative pathology of 28 people reached the level of MP5, the rate of pCR was 10.4%. cut-off to the end of follow-up, and followed up to the patients. 313 people, follow up rate 91.3%.2. effect factors analysis: pCR as a therapeutic evaluation index, no papillary depression (P=0.008), molybdenum target without calcification (P=0.009), NAC after the examination of no obvious mass (P0.001), non Luminal (P=0.044), PR negative (P=0.028) pCR rate is higher, and the difference is statistically significant. The pCR rate of three negative people is higher than that of the The difference between the type and type LuminalB was statistically significant (P=0.008). The number of parturition was less than 1 times (P=0.028), and there was no obvious mass (P0.001) after NAC, and the high expression of the histopathology of Ki67 high expression (P=0.039) before NAC was higher, and the difference was statistically significant in the pre.NAC T color Doppler stage (P=). 0.028), Luminal typing (P=0.037), histological grade (P=0.022), chemotherapy cycle number (P=0.022) and pathological major remission have significant correlation. Two yuan Logistic regression analysis shows whether there are obvious masses (P=0.012) after NAC and whether there is milk head depression before NAC (P=0.026) as an independent predictor of pCR; histological grade (P=0.) 024) whether there is an obvious mass (P=0.032) as an independent predictor of major pathological remission in the post NAC examination; chemotherapy (P=0.005) and the total number of chemotherapy cycles (P0.001) can be used as an independent predictor of clinical remission with the effect of.3. chemotherapy: in the new adjuvant chemotherapy of ET regimen, more than 6 cycles have a higher disease. Remission rate (27..5%VS 8.8%, P=0.004), CR rate (17.5%VS 3.4%, P=0.044) and clinical remission rate (80.0%VS 50%, P=0.003); higher chemotherapy dose intensity suggests better efficacy, but the difference does not have statistical significance.4. Qilu Hospital clinician habit research: NAC in the last 7 years (46.6%), CEF Scheme Application ratio The proportion of TEC programs increased year by year, and the proportion of the NAC scheme was significantly different in different years (P0.001). The factors affecting the choice of NAC scheme by clinicians were analyzed, the age of the treatment, the age of the patients, whether there were nipple spills at the first diagnosis, the molecular classification was Luminal, the histological grade, and the NAC E before. The status of R and PR has a significant effect on the choice of chemotherapy regimens by clinicians. But only the years of treatment and the age of the patients are the factors that guide the prognostic factors of the independent impact factor (P=0.013, P=0.004).5. for the clinicians to choose the chemotherapy regimen: different recurrent and metastatic sites (P=0.003), and whether myelosuppression (P=0.013) occurs during NAC. The condition of postoperative radiotherapy (P0.001), the condition of postoperative limb lymphedema (P=0.048), whether it reached the large part of the pathological remission (P=0.044), whether it reached pCR (P=0.005), NAC after Luminal type (P=0.004), before NAC phase ultrasound stage (P0.001), the T body stage and the postoperative metastasis value were all significantly related to the survival rate of the patients. In the COX regression, we can see whether the ratio of the metastatic LN to the detected LN is greater than 30% (P=0.003), whether it is Luminal type (P=0.002) or not (P=0.02) can be an independent factor affecting the survival of NAC patients of breast cancer. Histological grading, whether or not NAC can touch the mass as an independent predictor of major pathological remission; NAC scheme and cycle number are independent influence factors of clinical remission factor.2. chemotherapy options affect chemotherapy effect, and full foot therapy chemotherapy suggests better effect of.3. clinicians to further strengthen the individual consciousness of NAC, so that patients More benefit from the pathological transfer of.4. after chemotherapy with LN/ to detect whether LN is more than 30% (P=0.003), whether or not Luminal type (P=0.002), and whether or not to reach a major pathological remission (P=0.02) can be an independent factor affecting the survival of NAC patients of breast cancer.
【学位授予单位】：山东大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R737.9

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