本文選題：乳腺癌 + 新輔助化療�。� 參考：《山東大學(xué)》2017年碩士論文

【摘要】：目的近年來,我國的女性乳癌發(fā)病率迅猛上升,現(xiàn)已嚴(yán)重威脅著患病者的生命健康。乳腺癌治療的方式也從傳統(tǒng)的單純手術(shù)轉(zhuǎn)化為以手術(shù)方式為主的綜合治療,因此,新輔助化療應(yīng)運而生,并且已發(fā)展成為各階段乳腺癌治療的一種選擇,它的應(yīng)用使得眾多不可手術(shù)的乳腺癌患者獲得手術(shù)機會、甚至是保乳機會,并且達(dá)到了改善預(yù)后、延長生存的目的。但是仍然留有20%的患者不能獲益于新輔助化療。因此,發(fā)展一種可靠的、個體化的新輔助化療方案,以提高乳腺癌患者的生存質(zhì)量以及改善其預(yù)后顯得尤為重要。方法搜集2010年1月到2016年8月收治于山東大學(xué)齊魯醫(yī)院乳腺外科的女性乳腺癌NAC患者的相關(guān)臨床、病理資料,對其展開回顧性分析。收集的信息主要包括:患者年齡、婚育史、哺乳情況、身高體重(BMI)、初診時及新輔助化療后的臨床查體情況(包括腫塊的大小、位置、距乳暈距離以及乳房伴隨表現(xiàn)、淋巴結(jié)的狀態(tài)等)、初診時及NAC后的的影像學(xué)表現(xiàn)(包括彩超、鉬靶)及實驗室檢查結(jié)果、新輔助化療前后的病理學(xué)診斷(腫瘤類型、組織學(xué)分級、免疫組化指標(biāo)等)、淋巴結(jié)狀態(tài)、以及進(jìn)行的NAC方案、周期、劑量,患者接受的手術(shù)方式,通過隨訪電話得到患者后續(xù)的化療、放療、內(nèi)分泌治療狀態(tài),化療期間副反應(yīng),以及術(shù)后轉(zhuǎn)移、復(fù)發(fā)和生存狀況。治療前的臨床分期參考UICC的TNM分期之乳腺癌標(biāo)準(zhǔn);臨床評估參照國際抗癌協(xié)會制訂公布的實體腫瘤療效評價方法,即Resistl標(biāo)準(zhǔn);病理學(xué)評估參照Miller Payne(MP)病理評價方法;使用Luminal分型對NAC患者進(jìn)行分子亞型的劃分。應(yīng)用SPSS 23.0軟件對收集的數(shù)據(jù)進(jìn)行統(tǒng)計學(xué)處理:采用卡方檢驗分析分類變量與NAC療效的關(guān)系;采用T檢驗來分析連續(xù)性變量與NAC療效的關(guān)系;采用配對檢驗(卡方或T檢驗)分析化療前后臨床生物學(xué)及病理學(xué)指標(biāo)的改變;應(yīng)用多元Logistic回歸來分析單因素分析存在統(tǒng)計學(xué)意義的因素;采用Kaplan-Meier法及C0X回歸來分析不同臨床病理學(xué)指標(biāo)影響患者預(yù)后的作用大小。以P0.05為差異具有統(tǒng)計學(xué)意義。結(jié)果1.研究納入343名乳腺癌新輔助化療患者,化療結(jié)束后均行手術(shù)治療,術(shù)后病理28人達(dá)到MP5級,pCR率10.4%。截止至隨訪結(jié)束,共隨訪到患者313人,隨訪率 91.3%。2.療效影響因素分析:以pCR作為療效評價指標(biāo)時,不伴有乳頭凹陷(P=0.008),鉬靶無鈣化灶(P=0.009),NAC 后查體無明顯腫塊(P0.001),非 Luminal 型(P=0.044),PR陰性者(P=0.028)的pCR率較高,且差異有統(tǒng)計學(xué)意義。三陰性者的pCR率高于其他類型,且與LuminalB型之間的差異具有統(tǒng)計學(xué)意義(P=0.008)。以病理大部緩解作為療效評價指標(biāo)時,分娩次數(shù)≤1次(P=0.028),NAC后查體無明顯腫塊(P0.001),NAC前Ki67高表達(dá)者(P=0.039)的病理大部緩解率較高,且差異有統(tǒng)計學(xué)意義。NAC前T彩超分期(P=0.028)、Luminal分型(P=0.037)、組織學(xué)分級(P=0.022)、化療周期數(shù)(P=0.022)與病理大部緩解之間均具有顯著相關(guān)性。二元Logistic回歸分析可見,NAC后查體是否有明顯腫塊(P=0.012)及NAC前是否有乳頭凹陷(P=0.026)可作為pCR的獨立預(yù)測因子;組織學(xué)分級(P=0.024)、NAC后查體是否有明顯腫塊(P=0.032)可以作為病理大部緩解的獨立預(yù)測因子;化療方案(P=0.005)及化療周期總數(shù)(P0.001)可以作為臨床緩解的獨立預(yù)測因子。3.化療用藥對療效的影響:在ET方案新輔助化療中,完成≥6個周期者具有更高的病理大部緩解率(27..5%VS 8.8%,P=0.004)、CR 率(17.5%VS 3.4%,P=0.044)和臨床緩解率(80.0%VS 50.0%,P=0.003);較高的化療劑量強度提示更好的療效,但差異不具有統(tǒng)計學(xué)意義。4.齊魯醫(yī)院臨床醫(yī)生用藥習(xí)慣研究:近7年來,NAC以ET方案為主(46.6%),CEF方案應(yīng)用比例逐年減少,TEC方案應(yīng)用比例逐年提高,且不同年份、NAC方案所占比例之間具有顯著性差異(P0.001)。分析影響臨床醫(yī)生選擇NAC方案的因素,可見治療的年份、患者年齡、初診時查體是否有乳頭溢液、分子分型是否為Luminal型、組織學(xué)分級、NAC前ER和PR的狀態(tài)都對臨床醫(yī)生選擇化療方案造成顯著性影響。但僅有治療年份和患者的年齡是指導(dǎo)臨床醫(yī)生選擇化療方案的獨立影響因子(P=0.013、P=0.004)。5.預(yù)后影響因素分析:不同的復(fù)發(fā)轉(zhuǎn)移部位(P=0.003)、NAC期間是否出現(xiàn)骨髓抑制(P=0.013)、術(shù)后放療情況(P0.001)、術(shù)后患肢淋巴水腫的情況(P=0.048)、是否達(dá)到病理大部緩解(P=0.044)、是否達(dá)到pCR(P=0.005)、NAC后是否屬于Luminal型(P=0.004)、NAC前T彩超分期(P0.001)、T查體分期(P0.001)以及術(shù)后轉(zhuǎn)移LN/檢出LN值(P=0.001)均與患者的生存率顯著相關(guān)。納入COX回歸,可看出手術(shù)病理查見轉(zhuǎn)移LN占檢出LN的比例是否大于30%(P=0.003)、是否為Luminal型(P=0.002)、是否達(dá)到病理大部緩解(P=0.02)均可以作為影響乳腺癌NAC患者生存期的獨立因子。結(jié)論1.NAC后查體是否可觸及腫塊為pCR的獨立預(yù)測因子;組織學(xué)分級、NAC后是否可觸及腫塊為病理大部緩解的獨立預(yù)測因子;NAC方案及周期數(shù)為臨床緩解的獨立影響因子。2.化療方案的選擇影響化療效果,且足量足療程的化療提示更好的效果。3.臨床醫(yī)生有待進(jìn)一步強化NAC個體化意識,使患者更多的受益于化療。4.術(shù)后病理轉(zhuǎn)移LN/檢出LN是否大于30%(P=0.003)、是否為Luminal型(P=0.002)、是否達(dá)到病理大部緩解(P=0.02)可以作為影響乳腺癌NAC患者生存期的獨立因子。
[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.
【學(xué)位授予單位】：山東大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R737.9

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6 ;可手術(shù)NSCLC的化療及其爭議[N];中國醫(yī)藥報;2003年

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8 王杰軍 許青;乳腺癌新輔助化療發(fā)展概要[N];科技日報;2001年

9 吳志;新輔助化療+靶向治療“狙擊”乳腺癌[N];中國醫(yī)藥報;2009年

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2 張帥;加速分割調(diào)強適形放療在鼻咽癌中的臨床應(yīng)用與新輔助化療的研究及探討[D];山東大學(xué);2016年

3 朱聞捷;乳腺癌新輔助化療療效相關(guān)因素的探索及療效預(yù)測模型的建立[D];北京協(xié)和醫(yī)學(xué)院;2016年

4 汪令成;新輔助化療對不同分子亞型晚期乳腺癌的療效和預(yù)后的臨床研究[D];武漢大學(xué);2015年

5 梁云;子宮頸癌新輔助化療組織學(xué)療效評價及相關(guān)免疫因素的研究[D];浙江大學(xué);2017年

6 李雄;宮頸癌新輔助化療敏感性預(yù)測因素分析[D];華中科技大學(xué);2015年

7 陳燦銘;局部晚期乳腺癌新輔助化療的研究[D];復(fù)旦大學(xué);2004年

8 陳盛;乳腺癌新輔助化療后殘留腫瘤自噬及其與患者預(yù)后的相關(guān)性[D];復(fù)旦大學(xué);2012年

9 何海飛;蛋白質(zhì)指紋圖譜在乳腺癌個體化新輔助化療中的應(yīng)用[D];浙江大學(xué);2011年

10 尹波;乳腺癌新輔助化療的MRI研究[D];復(fù)旦大學(xué);2010年

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5 桑蝶;Ki67與乳腺癌臨床病理特征及新輔助化療療效的相關(guān)性[D];北京協(xié)和醫(yī)學(xué)院;2015年

6 陳萌;乳腺癌新輔助化療前后Ki-67變化的臨床意義[D];河北醫(yī)科大學(xué);2015年

7 陳航航;FOXP3~+Tregs對乳腺癌新輔助化療效果的預(yù)測價值[D];鄭州大學(xué);2015年

8 張子敬;乳腺癌新輔助化療的病理學(xué)指標(biāo)及動態(tài)增強核磁共振研究[D];復(fù)旦大學(xué);2013年

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10 李俊勇;新輔助化療對浸潤性膀胱癌術(shù)后生存影響的Meta分析[D];蘭州大學(xué);2015年

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