p53蛋白表达与乳腺癌新辅助化疗疗效的关系

采用新辅助化疗TE方案对50例Ⅱa～Ⅲb期乳腺癌患者治疗4个周期，化疗前用粗针穿刺获得乳腺癌组织病理诊断，同时用免疫组化方法检测p53蛋白表达。结果显示，p53蛋白表达阴性者有效率82％，阳性者47％，二者差异有显著性（P〈0．05）。提示p53蛋白表达水平是乳腺癌TE方案新辅助化疗疗效的重要预测因子，阳性者对TE方案疗效欠佳。     

乳腺癌肿瘤生物学因子检测对新辅助化疗方案选择的指导作用

目的探讨p53、C-erbB-2、Ki-67蛋白表达的检测对新辅助化疗方案选择的指导作用。方法采用新辅助化疗TE方案对50例Ⅱa～Ⅲb期乳腺癌患者治疗两周期,化疗前用粗针穿刺获得乳腺癌组织病理诊断,同时用免疫组化方法检测p53、C-erbB-2、Ki-67蛋白表达。结果p53蛋白表达阴性者有效率高于p53阳性者;Ki-67表达≥30％者有效率高于Ki-67表达〈30％者。结论p53、Ki-67蛋白表达水平是乳腺癌TE方案新辅助化疗疗效的重要预测因子,表达阴性者对TE方案敏感。     

C-erbB-2、p53、Ki-67及VEGF在乳腺癌组织中的表达及临床意义

目的进一步探讨乳腺癌的发生、发展机制。方法采用免疫组化SP法检测39份乳腺癌组织中人表皮生长因子受体2（C-erbB-2）、突变型p53蛋白（p53）、增殖细胞核抗原（Ki-67）及血管内皮生长因子（VEGF）表达情况;Spearman等级相关分析法分析四者间及与乳腺癌临床病理特征的关系。结果乳腺癌患者C-erbB-2、p53、Ki-67及VEGF的阳性表达率分别为46.15%、46.15%、71.79%5、8.97%;C-erbB-2表达与淋巴结转移、雌激素受体、孕激素受体相关,p53与淋巴结转移相关,Ki-67及VEGF与肿瘤直径、淋巴结转移相关;四指标之间均呈正相关（除p53与VEGF无相关性外）。结论 C-erbB-2、p53、Ki-67及VEGF检测对提示乳腺癌预后有重要意义。     

乳腺癌组织p16基因甲基化与ER、PR、HER2及p53表达的关系

目的探讨乳腺癌组织中p16基因甲基化与相关受体表达的相关性,进一步提高乳腺癌的诊断水平。方法采用甲基化特异性PCR（MSP）法检测86份乳腺癌组织及40份乳腺癌患者血清中p16基因的甲基化状态;采用免疫组化sP法检测乳腺癌组织中雌激素受体（ER）和孕激素受体（PR）、人类表皮生长因子受体2（HER2）及p53基因表达,分析各指标之间及与乳腺癌之间的关系。结果乳腺癌组织及血清中p16基因甲基化率分别为29．1％、27．5％;15例ER、PR、HER2均为阴性表达者（三阴乳腺癌）,p16基因甲基化率为86．67％（13／16）,非三阴乳腺癌71例,p16基因甲基化率为16．9％（12／71）,P〈0．01。p16基因甲基化与ER、PR蛋白表达呈负相关（r=-0．425、-0．512,P均〈0．05）,与HER2表达呈正相关（r=0．443,P〈0．05）;与p53表达无明显相关性。结论p16基因甲基化是乳腺癌中常见的分子改变,其与ER、PR、HER2联合检测可作为乳腺癌早期诊治及预后判断的重要指标。     

乳腺癌组织中HER-2的表达变化及意义

目的观察乳腺癌组织中人表皮生长因子受体2（HER-2）的表达变化,并探讨其意义。方法取56例乳腺癌组织及20例正常乳腺组织,采用免疫组化染色法检测HER-2蛋白,半定量RT-PCR法检测HER-2 mRNA。结果乳腺组织中HER-2蛋白阳性32例,HER-2mRNA表达量为0．64385±0．256418,正常乳腺组织中分别为1例、0．45183±0．00116,两者相比,P〈0．001;HER-2 mRNA表达量与乳腺癌TNM分期有关（P〈0．001）。结论乳腺癌组织中HER-2高表达在乳腺癌的发生发展中起重要作用。     

三阴性乳腺癌组织中p53、Ki-67、EGFR的表达变化及意义

目的观察三阴性乳腺癌（TNBC）组织中p53、Ki-67、表皮生长因子受体（EGFR）表达变化,探讨其临床意义。方法采用免疫组化SP法检测137例TNBC组织中p53、Ki-67、EGFR的表达,分析其与TNBC临床病理特征及预后的关系。以非三阴性乳腺癌（N—TNBC）组织为对照。结果TNBC组织中p53、Ki-67、EGFR阳性表达率分别为55．7％、94．2％、65．0％,均明显高于N-TNBC的43．6％、90．7％、48．1％（P均〈0．05）;p53、Ki-67、EGFR阳性表达与TNBC大小、组织学分级、TNM分期、脉管内癌栓、淋巴结转移及预后有关（P均〈0．05）,与患者年龄和绝经状态无关（P〉0．05）。术后3a生存的TNBC患者,其癌组织中p53、Ki-67、EGFR阳性表达率为53．8％、94．1％、61．0％,术后生存5a者分别为51．8％、92．7％、56．9％,均高于术后生存3、5a的N-TNBC患者（P均〈0．05）。结论TNBC组织中p53、Ki-67、EGFR的表达均上调,其可作为TNBC的重要的预后指标,其中EGFR还可以作为靶向治疗的重要参考依据。     

新辅助化疗对乳腺癌雌激素受体和C-erbB-2表达的影响

对91例乳腺癌患者实施新辅助化疗.化疗前后检测乳腺癌组织中雌激素受体(ER)、C-erbB-2的变化.结果 显示,新辅助化疗前后有15例ER状态发生变化,有12例C-erbB-2状态发生变化,但差异均无统计学意义.认为新辅助化疗能使部分乳腺癌组织中ER、C-erbB-2的表达发生变化,但无显著影响.     

乳腺癌组织中p53的表达变化及意义

目的观察p53在乳腺癌组织中的表达,探讨其意义。方法采用免疫组织化学法检测127例乳腺癌组织中的p53。结果乳腺癌组织中p53阳性率为49％,其表达与临床分期、淋巴结转移有关（P〈0．05）,与年龄、肿瘤大小及组织学分型无关（P〉0．05）。结论053在乳腺癌组织中高表达,可做为判断乳腺癌转移的指标之一。     

乳腺癌组织中ER、PR、Ps2、C-erbB-2表达与新辅助化疗疗效的关系

目的探讨乳腺癌组织中雌激素受体（ER）、孕激素受体（PR）、雌激素调节蛋白（Ps2）和C-erbB-2的表达与新辅助化疗（NACT）疗效的关系。方法采用免疫组化法检测50例接受NACT的乳腺癌患者化疗前的ER、PR、Ps2、C-erbB-2,并分析其与新辅助化疗效果的关系。结果 ER阳性和PR阳性者NACT有效率分别为59.4%和60.6%,明显低于ER阴性者的83.3%和PR阴性者的82.4%（P均〈0.05）,Ps2阳性者与Ps2阴性者及C-erb2过表达者与非过表达者相比P均〉0.05。结论乳腺癌组织中ER、PR表达与NACT疗效相关,Ps2、C-erbB-2表达与NACT疗效无关。ER、PR阴性的乳腺癌患者对化疗更敏感。     

ER、PR和HER-2的表达状况与乳腺癌新辅助化疗反应的关系

目的 探讨乳腺癌患者ER、PR和HER-2表达与新辅助化疗临床疗效的关系.方法 我科自2006年5月至2008年5月间进行新辅助化疗乳腺癌患者共43例,均采用TAC方案进行化学治疗(紫杉醇175 mg/m2,吡柔比星50 mg/m2,环磷酰胺500 mg/m2),21 d为一个疗程,进行2到4个疗程后进行乳腺癌保乳手术或乳腺癌改良根治术,化疗前标本与术后标本均进行ER、PR和HER-2的检测.结果 32例达到临床部分缓解,总有效率为74.4% (32 /43),11例患者处于疾病稳定状态,无临床完全缓解及疾病进展病例,总获益率100%.病理完全缓解5例(11.6%).其中ER阴性患者的有效率89.5%,ER阳性患者的有效率62.5%,PR阴性患者的有效率94.1%,PR阳性患者的有效率61.5%,ER阳性组与ER阴性组、PR阳性组与PR阴性组化疗有效率差异均有统计学意义.HER-2过度表达组有效率66.7%,HER-2非过度表达组有效率76.5%,二者之间无统计学意义.在所有43例患者中ER、PR和HER-2表达在化疗前后均无改变.结论 ER 或PR 阴性的乳腺癌病人对化疗更敏感,新辅助化疗对ER、PR和HER-2表达无影响.     

TAC、TEC方案新辅助化疗治疗乳腺癌效果比较

目的比较TAC、TEC两种新辅助化疗方案治疗乳腺癌的疗效。方法 139例原发性乳腺癌患者,随机分为TAC组71例和TEC组68例,分别采用TAC（多西他赛＋吡柔比星＋环磷酰胺）方案及TEC（多西他赛＋表柔比星＋环磷酰胺）方案进行4~6周期的新辅助化疗,观察肿瘤、腋窝淋巴结的变化以及不良反应发生情况。结果 TAC组总有效率（RR）、病理完全缓解率（pCR）、临床完全缓解率（cCR）、临床部分缓解率（cPR）以及病情稳定（SD）率分别为88.7%、11.3%、28.2%、60.6%和11.3%,TEC组分别为86.8%、10.3%、26.5%、60.3%和13.2%,两组相比P均〉0.05。化疗过程中两组白细胞下降、血小板减少、便秘、心脏毒性、肝肾功能异常发生率相比P均〉0.05。TAC组胃肠道反应（恶心或呕吐）发生率为46.5%,低于TEC组的66.2%（P〈0.05）。两组手术切除率均达100%。结论用TAC、TEC方案行乳腺癌新辅助化疗疗效满意,不良反应少。     

Early prediction of response to neoadjuvant chemotherapy using contrast-enhanced ultrasound in breast cancer

Early prediction of non-response is essential in order to avoid inefficient treatments. The objective of this study was to determine the contrast-enhanced ultrasound (CEUS) for early predicting pathologic complete response (pCR) to neoadjuvant chemotherapy (NAC) in breast cancer patients.Between March 2018 and October 2019, 93 consecutive patients with histologically proven breast cancer scheduled for NAC were enrolled. Conventional ultrasound and CEUS imaging were performed before NAC and after two cycles of NAC. CEUS parameters were compared with pathologic response. Multiple logistic regression analyses were utilized to explore CEUS parameters to predict pCR, and receiver operating characteristic analysis was used to evaluate the predictive ability.Therapeutic response was obtained from 25 (27%) patients with pCR and 68 (73%) with non-pCR. Compared to non-pCR, pCR cases have a significantly higher proportion of homogeneous enhancement feature (56% vs 14%, P < .001) and centripetal enhancement (52% vs 23%, P = .012). A significant decrease in peak intensity (PI) was observed after two cycles of NAC. Compared with non-pCR patients, the kinetic parameters PI change (PI%) was higher in pCR patients (P < .001). Multiple logistic regression demonstrated two independent predictors of pCR: internal homogeneity (odds ratio, 4.85; 95% confidence interval: 1.20–19.65; P = .027) and PI% (odds ratio, 1.08; 95% confidence interval: 1.02–1.15; P = .007). In receiver operating characteristic curve analysis, internal homogeneity and PI%, with area under curve of 0.71 and 0.84, predicted pCR with sensitivity (56%, 95%) and specificity (85%, 70%), respectively.Internal homogeneity and PI% of CEUS may be useful in the noninvasive early prediction of pCR in patients with breast cancer.     

Role of P53 and BCL-2 in high-risk breast cancer patients treated with adjuvant anthracycline-based chemotherapy

Purpose: Adjuvant therapy has become an integral component of the management of primary high-risk breast cancer patients. However, a considerable fraction of women receive no benefit from this treatment. This study investigates whether a number of biopathological factors can influence the outcome of patients submitted to adjuvant chemotherapy involving the use of high-dose epirubicin and cyclophosphamide. Methods: One hundred and fifty-seven primary breast cancer patients, considered at high risk according to the St. Gallen Meeting Consensus Conference, were evaluated immunohistochemically for estrogen, progesterone receptors, p53, bcl-2, HER-2/neu, and Ki-67, of which the results were correlated with patient outcome. Results: Results obtained demonstrated that p53 is a significant predictor of disease-free survival (DFS P < 0.0001) and overall survival (OS P=0.0002) both in ductal and lobular carcinomas, whereas bcl-2 expression seems to be of prognostic value only in lobular carcinomas (DFS P=0.01; OS P=0.02). Conclusions: This data indicates that in high-risk breast cancer patients the immunohistochemical evaluation of p53 and bcl-2 may be of clinical value in distinguishing different responses to adjuvant anthracycline-based chemotherapy. Received: 4 October 1999 / Accepted: 10 April 2000     

Adjuvant chemotherapy does not affect employment in patients with early-stage breast cancer

OBJECTIVE: To assess the impact of adjuvant chemotherapy for the management of breast cancer on subsequent patient employment. DESIGN: Retrospective cohort study. SETTING: University-affiliated community hospital cancer center. PATIENTS: Patients who were 18 to 65 years old and were diagnosed as having breast cancer stages 0, I, II, and IIIa between January 1986 and January 1991 were contacted and asked whether they had been employed at the time of the diagnosis. The 145 patients who had breast cancer and who had been working at the time of diagnosis completed a questionnaire, which included questions regarding demographic characteristics, employment history, and the reasons for any period of unemployment. The 76 patients who had received adjuvant chemotherapy were compared with the 69 who had not. MEASUREMENTS AND RESULTS: The main endpoint was return to work by one, three, six, and 12 months after surgery. Of the 76 patients who had received chemotherapy, 70 (92%) had resumed work by 12 months after treatment began. Of the 69 who had not been treated with chemotherapy, 65 (94%) had resumed work in 12 months. The proportions of patients who had returned to work by one, three, and six months were similar in the two groups. Regression analyses demonstrated no significant confounding or interaction of adjuvant treatment with age, menopausal status, marital status, years of education, or type of job in regard to return to work. CONCLUSIONS: Adjuvant chemotherapy does not delay or prevent return to work in women treated for early-stage breast cancer. Presented as a poster abstract at the San Antonio Breast Cancer Symposium, November 5–6, 1993. Supported in part by a Rochester General Hospital Foundation Research Grant.     

健脾扶正方对接受新辅助化疗胃癌患者近期疗效和免疫功能的影响

目的:探讨健脾扶正方应用于胃癌患者新辅助化疗的疗效.方法:将90例进展期胃癌患者按照随机数字表法分为2个组,每组45例.2组均接受新辅助化疗和胃癌根治术,中药组在新辅助化疗期间应用中药健脾扶正方,对照组仅接受新辅助化疗.比较2组近期疗效和免疫功能.结果:化疗后中药组客观有效率、疾病控制率、R0切除率均高于对照组(P＜0...     

Clinical study on Yanghe decoction in improving neo-adjuvant chemotherapy efficacy and immune function of breast cancer patients

Introduction:Neoadjuvant chemotherapy (NAC) plays an important role in downgrading preoperative tumor size, providing information on regimen activity, and increases treatment efficacy in breast cancer patients. An increasing number of patients have sought Traditional Chinese Medicine (TCM) during NAC to relieve discomfort, regulate immune function, and improve survival. However, limited evidence is available on how concurrent TCM treatment combined with NAC affects tumor response. This study aims to assess the efficacy of Yanghe decoction, a classical warming Yang formula, on pathological complete response (pCR) and explore its mechanism via the phosphatidylinositol-3-kinase/ protein kinase B/nuclear factor kappa-B (PI3K/Akt/NF-κB) pathway-mediated immune-inflammation microenvironment.Methods:A single-center, randomized, placebo-controlled, double-blinded randomized control trial (RCT) was designed. This trial aims to recruit 128 participants with breast cancer scheduled to receive NAC in China. All participants will be randomly assigned (1:1) to the Neo-Yanghe group (Yanghe decoction plus NAC) or the control group (placebo plus NAC). The primary outcome will be evaluated by the proportion of participants achieving pCR. The secondary outcomes include the expression level of PI3K/Akt/NF-κB pathway-related proteins, the objective response rate, the time to response, serum level of immune-inflammatory indicators, quality of life, disease-free survival, and overall survival.Discussion:This study will be the first RCT to evaluate the efficacy of Yanghe decoction combined with NAC in treating breast cancer patients, and elucidate the antitumor mechanism via the PI3K/Akt/NF-κB pathway-mediated immune-inflammation microenvironment. If possible, Neo-Yanghe treatment pattern will be a better pharmacological intervention to manage breast cancer than chemotherapy alone. The results of the trial will provide research-based evidence for the development of integrated Chinese and Western medicine guidelines and expert consensus.Trial registration: Chinese Clinical Trial Registry ChiCTR-INR-2000036943. Registered on September 28, 2020 (https://www.chictr.org.cn/hvshowproject.aspx?id=57141).     

乳腺癌组织中EGF和ALDH1A1的表达及其临床意义

目的 研究表皮生长因子(EGF)与乙醛脱氢酶(ALDH1A1)在正常乳腺组织及乳腺癌组织中的表达及意义,探讨EGF在乳腺癌干细胞演进过程中的作用.方法 采用RT-PCR和免疫组化方法分别检测24例正常乳腺组织和45例乳腺浸润性导管癌组织中EGF和ALDH1A1的表达情况.结果 RT-PCR结果显示,乳腺癌中EGF与ALDH1A1的mRNA水平高表达,在正常乳腺组织中低表达或不表达,两组比较P＜0.01.免疫组化结果显示,EGF在正常乳腺与乳腺癌中的表达分别为20.8％和75.6％,ALDH1A1在正常乳腺与乳腺癌中的表达分别为16.7％与66.4％,乳腺癌中EGF与ALDH1A1蛋白水平表达明显高于正常组织(P＜0.01).EGF与ALDH1A1两者在乳腺癌中表达存在正相关(P＜0.05).EGF的表达与发病年龄、肿瘤大小、组织学分型、有无淋巴结转移、PR表达无相关性,与ER表达呈正相关(P＜0.01);ALDH1A1的表达与发病年龄、肿瘤大小、有无淋巴结转移、ER、PR表达无相关性,与组织学分型呈正相关(P＜0.05).结论 EGF与ALDH1A1在乳腺癌组织中的表达高于正常乳腺组织,EGF与乳腺癌干细胞的发生发展关系密切.     

Correlation between pretherapeutic d-dimer levels and response to neoadjuvant chemotherapy in patients with advanced esophageal cancer

SUMMARY.  Neoadjuvant chemotherapy may improve survival of responders in esophageal cancer patients but is useless and harmful in non-responders. Thus, it is important to predict the effect of the chemotherapy, and that any predictor must be applicable clinically. The aim of this study is to examine the correlation between pretherapeutic hypercoagulopathy as determined by plasma d -dimer levels and response to chemotherapy. In 71 patients with esophageal cancer who underwent neoadjuvant chemotherapy (cisplatin, adriamycin and 5-fluorouracil) followed by surgery, plasma d -dimer levels were measured before chemotherapy and the clinical and pathological responses to chemotherapy were assessed at 4 weeks after therapy (after surgery). Pretherapeutic plasma d -dimer level was significantly lower in clinical responders (complete response/partial response [CR/PR]; 0.62 ± 1.10 µg/mL, mean ± SD) than in non-responders (no change/progressive disease [NC/PD]; 1.15 ± 1.08 µg/mL, P  = 0.0491), and in pathological responders (Grade 1b-3; 0.62 ± 1.11 µg/mL) and non-responders (Grade 0–1a; 1.15 ± 1.05 µg/mL, P  = 0.0107). The optimal cut-off level of the plasma d -dimer levels for predicting clinical and pathological responses was 0.6 µg/mL. Then, sensitivity and specificity for the prediction of CR/PR were 68% and 73%, and those for Grade 1b–3 were 91% and 69%, respectively. Our results suggested that pretherapeutic plasma d -dimer level correlated significantly with clinical and pathological responses to chemotherapy. Pretherapeutic plasma d -dimer level can be used as a predictor for chemosensitivity.