Ki-67表达水平检测在乳腺癌新辅助化疗疗效评估中的价值

目的:回顾性分析88例乳腺癌新辅助化疗前、后Ki-67在肿瘤组织的表达情况,探讨Ki-67表达与新辅助化疗疗效的关系,评价其在乳腺癌新辅助化疗中的预测作用.方法:选取2015年9月至2016年9月河北医科大学第四医院乳腺中心收治的88例Ⅱ-Ⅲ期乳腺癌患者,检测新辅助化疗前空芯针穿刺肿瘤组织及术后标本中Ki-67的表达,分析其与新辅助化疗疗效及临床相关病理因素的关系.结果:新辅助化疗的临床总有效率为59.09%(52/88),Ki-67高表达组对化疗敏感,化疗效果明显优于Ki-67低表达组(P<0.05);新辅助化疗可明显降低Ki-67的高表达率(P<0.01);新辅助化疗后Ki-67表达下降组化疗有效率显著高于其他组(P<0.05).结论:Ki-67在乳腺肿瘤组织中的表达可作为新辅助化疗疗效临床评价指标之一,预测新辅助化疗的疗效,为个体化治疗提供依据.     

Evaluation of ER and Ki-67 proliferation index as prognostic factors for survival following neoadjuvant chemotherapy with doxorubicin/docetaxel for locally advanced breast cancer

Background The aim of the study was to identify reliable predictive biological markers for treatment outcome following neoadjuvant adriamycin/docetaxel (AT) chemotherapy in locally advanced breast cancer patients. Materials and methods This study was a phase II study on AT neoadjuvant chemotherapy in locally advanced breast cancer patients. Patients received 50 mg/m² of doxorubicin intravenously (IV) over 15 min followed by docetaxel 75 mg/m² infused over 1 h, repeated every 3 weeks for three cycles. Surgery was performed within 3–4 weeks following the last cycle of chemotherapy. We analyzed the pre-treatment and post-treatment expression levels of ER, PgR, HER-2, Ki-67 proliferation index, and p53 and examined the correlation between the markers and clinical parameters with treatment response, overall survival and relapse-free survival following neoadjuvant treatment. Results From July 2001 to September 2004, 61 patients were enrolled. The meaningful parameters adversely influencing survival were post-treatment ER(−) status (P = 0.013) and post-treatment Ki-67 index above 1.0% (P = 0.013). At the multivariate level, the post-treatment Ki-67 proliferation index ≤ 1.0 was the only meaningful prognostic factor for better survival (P = 0.033). Notably, tumors with Ki-67 index ≤ 1.0 were more likely to express ER with statistical significance (P = 0.002). Tumors with ER(+) and Ki-67 index ≤ 1.0 showed the highest survival rate, followed by ER(+) and Ki-67 index > 1.0%, ER(−) and Ki-67 ≤ 1.0%, and ER(−) and Ki-67 > 1.0% with the worst survival (P = 0.033). Conclusion Collectively, post-treatment ER status and Ki-67 proliferation index were prognostic of overall survival following neoadjuvant AT chemotherapy.     

158例乳腺癌新辅助化疗疗效与Ki-67截断值的相关分析

  目的  探讨乳腺癌分子分型、ER、PR、Ki-67表达对新辅助化疗（neoadjuvant chemotherapy,NAC）疗效的预测价值,以及不同化疗方案和周期对疗效的影响。  方法  收集2015年1月至12月158例天津医科大学肿瘤医院行NAC的女性乳腺癌患者的临床资料,对比各分子分型及不同化疗方案疗效的差异,分析评价影响疗效的临床指标,及ER、PR、Ki-67预测NAC疗效的价值。  结果  158例患者中,其中5例HER-2阳性患者行曲妥珠单抗治疗,因病例数较少未纳入统计分析。Spearman相关分析显示,NAC疗效与ER、PR表达呈负相关,与Ki-67（截断值为25%）表达呈正相关（P < 0.05）;Luminal型和非Luminal型乳腺癌患者NAC疗效的病理评价为无效分别占10.1%和1.3%,差异具有统计学意义（P=0.033）;NAC < 4个疗程的疗效达Ⅲ级仅4.8%,显著低于NAC≥4个疗程的36.0%,差异具有统计学意义（P=0.016）。Logistic多因素分析显示化疗前Ki-67表达是影响NAC疗效的独立预测因素。  结论  根据化疗前Ki-67表达可粗略预测NAC疗效,但Ki-67截断值应依据检测机构的数据进行评定;Luminal型患者经NAC治疗后无效的概率较大,化疗不敏感时可考虑手术治疗。NAC < 4个疗程时NAC疗效降低,提示NAC足疗程是提高其疗效的条件之一。      

Ki-67在乳腺癌新辅助化疗中的作用及临床意义

新辅助化疗主要应用于局部晚期乳腺癌的治疗,疗效评价常用的指标为临床上缓解和病理学上缓解的程度.Ki-67是与细胞分裂增殖有关的核蛋白,已广泛应用于各种肿瘤的诊断及预后.多项临床研究资料表明Ki-67在判断乳腺癌新辅助化疗是否有效中显示出潜在的价值,现就Ki-67在乳腺癌新辅助化疗中的作用及临床意义作一综述.     

Docetaxel and high-dose epirubicin as neoadjuvant chemotherapy in locally advanced breast cancer

Purpose Epirubicin and docetaxel are two of the most active drugs against breast carcinoma. As the achievement of a pathological complete response (pCR) is important for survival of patients with locally advanced disease, we used both drugs as neoadjuvant chemotherapy.Patients and methods Women with locally advanced or inflammatory breast cancer received epirubicin 120 mg/m² followed by docetaxel 75 mg/m², both on day 1, every 21 days for four cycles. Lenograstim was administered for 10 days in all cycles.Results Of 51 patients included, 50 received a total of 188 cycles, with a median of 4 per patient. The median age was 47 years, tumour stage was IIIA in 14 patients and IIIB in 36. Oestrogen receptors were positive in 65% of tumours. There were 10 clinical complete responses (20%) and 29 partial responses (58%). Surgery consisted of mastectomy in 40 patients and tumorectomy in 6. After surgery, 9 pCR were recorded (18%). One patient progressed and died soon after the end of chemotherapy. After a median follow-up of 22 months, the median disease-free survival was 33.7 months. Grade 3/4 neutropenia was observed in 32% of patients, anaemia in 6%, and thrombocytopenia in 4%. Five patients had febrile neutropenia. There were no toxic deaths or grade 4 nonhaematological toxicities.Conclusions Docetaxel plus high-dose epirubicin showed promising activity in patients with locally advanced and inflammatory breast cancer, at the cost of moderate toxicity.     

BCRP和Ki-67与乳腺癌新辅助化疗疗效的关系

目的:探讨乳腺癌组织中乳腺癌耐药蛋白(breast cancer resistance protein,BCRP)和Ki-67的表达与新辅助化疗疗效之间的关系.方法:回顾性分析我科2012 年10月至2014年8 月收治的Ⅱ-Ⅲ期乳腺癌新辅助化疗患者65例,采用免疫组化方法检测BCRP和Ki-67的表达,分析BCRP、Ki-67的表达水平与新辅助化疗疗效的关系.结果:原发性乳腺癌组织中BCRP的阳性表达率为67.7%.BCRP的表达水平与新辅助化疗后病理组织学反应有关,组织学显著反应组(病理反应4~5级)BCRP的表达水平明显低于非显著反应组(病理反应1~3级),差异有统计学意义(x2=12.77,P=0.001).化疗前Ki-67高表达组临床缓解率明显高于低表达组(x2=17.72,P<0.00). 结论: 联合检测乳腺癌组织中BCRP和Ki-67 的表达水平对新辅助化疗疗效有一定的预测价值.     

三阴性乳腺癌新辅助化疗后组织中Ki-67表达变化及其与疗效和预后的相关性

目的:探讨三阴性乳腺癌(triple negative breast cancer,TNBC)新辅助化疗(neoadjuvant chemotherapy,NAC)后组织中Ki-67表达变化及其与疗效和预后的相关性.方法:选取我院2013年01月至2018年01月经病理确诊为TNBC的患者70例,根据免疫组化法检测NA...     

Elevated chemokine receptor CXCR4 expression in primary tumors following neoadjuvant chemotherapy predicts poor outcomes for patients with locally advanced breast cancer (LABC)

Purpose Patients with locally advanced breast cancer (LABC) have a poor outcome. A molecular predictor to identify at-risk patients is sorely needed. CXCR4 is a chemokine receptor that has been linked to breast cancer invasion and metastasis. We postulate that in patients with LABC, CXCR4 overexpression levels in cancer specimens following neoadjuvant chemotherapy predict cancer outcome. Experimental design 54 patients with LABC were prospectively accrued and analyzed. All had neoadjuvant chemotherapy and definitive surgical therapy. Study homogeneity was maintained by standardized treatment, surveillance, and compliance protocols. A 1 cm³ cancer from the surgical specimens of each patient was retrieved for analysis. CXCR4 levels were detected using Western blots, and results were quantified against 1 μg of protein from HeLa cells. CXCR4 expression was defined as low (<6.6-fold) or high (≥6.6-fold). Primary endpoints were cancer recurrence and death. Statistical analysis performed included independent samples t-test, chi-square test, Spearman Rank analysis, Kaplan-Meier survival analysis, log-rank test, and Cox proportional hazard model. Results With a median follow-up of 30 months, patients with high CXCR4 overexpression (≥6.6-fold) had a significantly higher incidence of recurrence (P = 0.0006) and cancer death (P = 0.0128) than those with low CXCR4 overexpression (<6.6-fold). The relative risks for recurrence and death in the high CXCR4 group were 27.3-fold (95% CI: 6.2–120.8; P = 0.001) and 4.8-fold (95% CI: 1.5–15.0; P = 0.0076) higher, respectively than those in the low CXCR4 group. Conclusion High CXCR4 overexpression in specimens from LABC patients receiving neoadjuvant chemotherapy was predictive of cancer outcome. Neal T. Holm was the recipient of the American Society of Clinical Oncology 2007 Merit Award     

Prognostic significance of Ki67 index after neoadjuvant chemotherapy in breast cancer

Purpose

Recently, Ki67 index (cell proliferation marker) has been attracting a considerable attention as a prognostic factor in breast cancer but the prognostic significance of Ki67 after neoadjuvant chemotherapy (NAC) has rarely been examined.

Experimental design

Primary breast cancer patients (n = 102) treated with NAC (sequential paclitaxel 12 cycles (q1w) and 5-FU/epirubicin/cyclophosphamide 4 cycles (q3w)) were recruited in the study. Ki67, estrogen receptor (ER) and progesterone receptor (PR) and breast cancer resistant protein (BCRP) and P-glycoprotein were determined by immunohistochemistry and HER2 was determined by FISH in tumor tissues obtained before and after NAC, and their association with patient prognosis (relapse-free survival) was examined.

Results

Of the 102 patients, pCR was achieved in 30 (29.4%). In the 72 non-pCR patients, Ki67 index significantly (P < 0.001) decreased after NAC. Ki67 index after NAC, but not Ki67 index before NAC, was significantly associated with a patient prognosis (P = 0.022). Multivariate analysis has shown that Ki67 index after NAC is a marginally significant (P = 0.05) prognostic factor and that other biomarkers including ER, PR, BCRP, and P-glycoprotein before and after NAC are not significant.

Conclusions

Ki67 after NAC, but not before NAC, is prognostic in breast cancer patients, and might be clinically useful in the prognosis prediction of patients who do not achieve pCR after NAC. On the other hand, BCRP and P-glycoprotein before and after NAC are unlikely to be useful as prognostic factors in these patients.     

The surgical management of patients following neoadjuvant chemotherapy for locally advanced breast cancer

The aim of this study was to evaluate the role of surgery in patients who achieve a complete clinical response (cCR) to neoadjuvant chemotherapy for locally advanced breast cancer. A retrospective study of patients with either large central (T2 >30 mm, N0 or N1, M0) or locally advanced (T3, N0 or N1, M0) tumours who received neoadjuvant chemotherapy followed by surgery to the breast and axilla and postoperative radiotherapy. All patients had operable disease at presentation. A total of 133 patients were included. Overall, 43 (32%) patients achieved a cCR following chemotherapy. Of these, 19 patients had no pathological evidence of disease in the breast (pCR) or on imaging or core biopsy and these patients received only adjuvant radiotherapy to the breast. A further 5 patients had no pathological evidence of cancer following breast surgery. 126 patients had an axillary clearance. Increasing response to chemotherapy was related to fewer pathologically involved nodes, but 7 of 24 (29%) patients with a pCR still had evidence of axillary metastases. This is the principal conclusion of the study at the present time. The patients were followed-up for a median of 30 months (range 5–83 months) with a local recurrence rate of 3.8%. There was no difference in either distant recurrence-free or overall survival between patients experiencing a pCR and the remainder.     

Indications for neoadjuvant treatment based on risk factors for poor prognosis before and after neoadjuvant chemotherapy alone in patients with locally advanced rectal cancer

IntroductionThe oncological benefit of neoadjuvant chemotherapy (NAC) alone for locally advanced rectal cancer (LARC) remains controversial. The aim of this study was to clarify the clinical risk factors for poor prognosis before and after NAC for decision making regarding additional treatment in patients with LARC.Materials and methodsWe examined a total of 96 patients with MRI-defined poor-risk locally advanced mid-low rectal cancer treated by NAC alone between 2006 and 2018. Survival outcomes and clinical risk factors for poor prognosis before and after NAC were analyzed.ResultsIn the median follow-up duration after surgery of 60 months (3–120), the rates of 5-year overall survival (OS), relapse-free survival (RFS), and local recurrence (LR) were 83.6%, 78.4%, and 8.2%, respectively. In the multivariate analyses, patients with cT4 disease had a significantly higher risk of poor OS (HR; 6.10, 95% CI; 1.32–28.15, P = 0.021) than those with cT3 disease. After NAC, ycN+ was significantly associated with a higher risk of poor OS (HR; 5.92, 95% CI; 1.27–27.62, P = 0.024) and RFS (HR; 2.55, 95% CI; 1.01–6.48, P = 0.048) than ycN-. In addition, patients with CEA after NAC (post-CEA) ≥ 5 ng/ml had a significantly higher risk LR (HR; 5.63, 95% CI; 1.06–29.93, P = 0.043).ConclusionNAC alone had an insufficient survival effect on patients with cT4 disease, ycN+, or an elevated post-CEA level. In contrast, NAC alone is a potential treatment for other patients with LARC.     

Ki-67表达与Ⅱ/Ⅲ期乳腺癌新辅助化疗疗效及预后的关系

目的:探讨乳腺癌组织中Ki-67 抗原（简称 Ki-67）表达与新辅助化疗(neoadjuvant chemotherapy,NAC)疗效的关系。寻找新辅助化疗有效的预测因子。方法:选取我院2012年6月至2017年6月收治的112例接受NAC治疗的Ⅱ/Ⅲ期乳腺癌患者作为研究对象。使用免疫组化方法检测NAC治疗前乳腺癌患者的Ki-67表达情况，化疗2~4周期后评估临床疗效。分析乳腺癌中Ki-67的表达与临床病理学特征的关系以及Ki-67的表达与NAC疗效的关系。结果:原发性乳腺癌组织中Ki-67的高表达率为65.18%，Ki-67的高表达与病理组织学分级（P=0.017）有关。Ki-67高表达的患者新辅助化疗后获得临床完全缓解（cCR）+临床部分缓解（cPR）的比率（89.0%）明显高于Ki-67低表达的患者新辅助化疗后获得cCR+cPR的比率（61.5%）（P=0.001）。中位随访时间 37个月，Ki-67高表达患者的无病生存时间（DFS）低于Ki-67低表达的患者（P=0.023），Ki-67高表达患者的总生存时间（OS）低于Ki-67低表达的患者（P=0.040）。结论:Ki-67的高表达与乳腺癌恶性程度密切相关，并可作为预测乳腺癌新辅助化疗敏感度及预后的独立指标。     

Ki-67与乳腺癌临床病理特征及新辅助化疗疗效的相关性

目的：分析Ki-67与乳腺癌临床病理特征对新辅助化疗（neoadjuvant chemotherapy,NCT）疗效和预后的影响,探讨NCT疗效的预测因素。方法用免疫组化法检测320例局部晚期乳腺癌患者癌组织中ER、PR、HER-2及Ki-67表达状况。进行NCT 4～6个周期后手术。分析临床病理特征与病理完全缓解率（patho-logic complete response,pCR）之间的关系。临床病理参数与疗效分析用χ2检验,影响预后因素用Cox多因素回归分析。结果 Ki-67表达与ER（r=－0.174,P=0.002）和PR（r=－0.132,P=0.019）呈负相关,与HER2（r=0.140, P=0.012）和乳腺肿瘤大小（r=0.132,P=0.019）呈正相关;ER阴性组pCR率显著高于ER阳性组（26.9%vs 7.4%,χ2=22.761,P=0.000）;PR阴性组pCR率显著高于阳性组（22.7%vs 10.9%,χ2=7.950,P=0.005）;Ki-67高表达组pCR率18.0%（41/228）优于Ki-67低表达组8.6%（8/92）（χ2=4.552,P=0.033）;化疗后Ki-67表达下降组pCR率19.8%（48/243）优于未下降组1.3%（1/77）（χ2=15.356,P=0.000）;各分子亚型间化疗疗效差异显著,Luminal A型pCR率为1.4%（1/71）,Luminal B型pCR率为15.3%（25/163）,HER2过表达型pCR率为31.3%（14/45）,三阴性型pCR率为22.0%（9/41）（χ2=20.639,P=0.000）;用Kaplan-Meier法进行生存分析,Ki-67低表达组无病生存时间（DFS）和总生存时间（OS）均优于Ki-67高表达组,两者均为P=0.034。结论 Ki-67高表达患者对化疗更敏感,但预后较差。化疗前Ki-67的表达和化疗后Ki-67变化是影响DFS独立的预后因素。ER、PR、Ki-67指数及分子分型可以作为NCT疗效的预测指标,Ki-67指数与ER、PR、HER2之间存在相关性。     

人表皮生长因子受体2阳性乳腺癌新辅助化疗后Ki-67表达变化与疗效的关系

目的探讨HER-2阳性乳腺癌患者新辅助治疗前、后Ki-67的表达变化与预后的关系。 方法回顾性分析2014年1月至2017年12月佛山市第一人民医院收治的85例乳腺癌患者的临床资料,术前均经空芯针吸穿刺活组织检查证实为HER-2阳性乳腺浸润性导管癌,之后接受新辅助化疗。采用χ²检验及Fisher确切概率法分析新辅助化疗前Ki-67表达与临床病理特征及新辅助化疗疗效之间的关系。采用χ²检验及Fisher确切概率法比较接受TcbH(多西他赛+卡铂+曲妥珠单克隆抗体)和AC-TH(表柔比星+环磷酰胺序贯多西他赛+曲妥珠单克隆抗体)2种方案的乳腺癌患者临床疗效和病理疗效的差异。根据新辅助化疗后激素受体(HR)状态,分成HR阴性组与HR阳性组,用χ²检验及Fisher确切概率法比较2组临床特征的差异。采用χ²检验及Fisher确切概率法分析新辅助化疗后Ki-67表达变化与患者疗效的相关性,采用Kaplan-Meier法描绘生存曲线并进行生存分析,用Log-rank法进行无复发生存(RFS)的组间比较,并根据HR状态进行亚组分析。(5)采用单因素和多因素Cox比例风险回归模型分析复发的影响因素。 结果新辅助化疗前Ki-67低表达患者22例,高表达患者63例。新辅助化疗前Ki-67低表达与高表达患者在年龄、月经状态、组织学分级、淋巴结转移状态、ER表达、PR表达、病理疗效及肿瘤大小和临床疗效方面比较,差异均无统计学意义(χ²＝0.000、0.296、0.186、0.276、0.010、0.021、1.401, P均>0.050;P＝0.646、0.569)。接受TcbH和AC-TH方案的患者临床疗效和病理疗效比较,差异均无统计学意义(P＝0.154; χ²＝0.232,P＝0.630)。新辅助化疗后,HR阴性51例,HR阳性34例。2组患者的手术方式、Miller-Payne分级、是否接受放射治疗、复发转移情况、Ki-67状态改变以及新辅助化疗方案比较,差异均无统计学意义(P＝0.157;χ²＝2.215、3.266、0.095、0.516、0.297,P均>0.050)。新辅助化疗后,21例Ki-67表达升高或无变化,64例Ki-67表达降低。Ki-67降低者的临床疗效及病理疗效均优于Ki-67升高或无变化者(P＝0.003; χ²＝8.729,P＝0.003)。亚组分析结果显示,在51例HR阴性患者中,Ki-67降低者病理疗效优于Ki-67升高或无变化者(χ²＝11.141,P＝0.001),但临床疗效比较,差异无统计学意义(P＝0.071);而在34例HR阳性患者中,Ki-67降低者临床疗效优于Ki-67升高或无变化者(P＝0.037),但病理疗效比较,差异无统计学意义(P＝0.672)。生存分析显示：新辅助化疗后Ki-67降低组RFS率明显高于Ki-67升高或无变化组(χ²＝26.275,P<0.001);在HR阴性及HR阳性患者中,新辅助化疗后Ki-67降低组RFS率均高于Ki-67升高或无变化组(χ²＝11.302、22.127,P均<0.001)。Cox风险比例回归模型分析显示,组织学分级3级、淋巴结转移是患者复发的独立危险因素(HR＝2.764、3.550,95%CI：1.104~6.919、1.026~12.281,P＝0.030、0.045),新辅助化疗后Ki-67表达降低是独立保护因素(HR＝0.197,95%CI：0.087~0.475,P<0.001)。 结论新辅助化疗后Ki-67表达变化与临床疗效及病理疗效之间存在相关性,可能是HER-2阳性乳腺癌患者RFS的独立影响因素。     

Ki-67与传统生物学标志物预测乳腺癌化疗药物敏感性的研究进展

乳腺癌是女性最常见的恶性肿瘤疾病。增殖抗原Ki-67、雌激素受体（ER）、孕激素受体（PR）及人表皮生长因子受体-2（CerbB-2）是乳腺癌病理检测常用生物标记物。多项研究证实,Ki-67高表达的乳腺癌化疗药物敏感性更高。ER、PR目前被广泛用于乳腺癌内分泌治疗的疗效预测,已有研究证实其可作为辅助化疗药物敏感性预测指标。CerbB-2阴性乳腺癌提示化疗敏感性较高已得到初步证实。本文阐述了有关Ki-67与传统生物学标志物预测乳腺癌辅助化疗药物敏感性的研究进展。     

Parental consanguineous marriages and clinical response to chemotherapy in locally advanced breast cancer patients

The main aim of the present study was investigating the association between parental consanguinity and clinical response to chemotherapy in females affected with locally advanced breast cancer. A consecutive series of 92 patients were prospectively included in this study. Clinical assessment of treatment was accomplished by comparing initial tumor size with preoperative tumor size using revised RECIST guideline (version 1.1). Clinical response defined as complete response, partial response and no response. The Kaplan-Meier survival analysis were used to evaluate the association of parental marriages (first cousin vs unrelated marriages) and clinical response to chemotherapy (complete and partial response vs no response). Number of courses of chemotherapy was considered as time, in the analysis. Kaplan-Meier analysis revealed that offspring of unrelated marriages had poorer response to chemotherapy (log rank statistic=5.10, df=1, P=0.023).     

Ki-67、CDK4表达与中晚期乳腺癌新辅助化疗效果的相关性分析北大核心

目的:分析Ki-67核抗原(Ki-67)、CDK4表达与中晚期乳腺癌新辅助化疗(NACT)效果的相关性。方法:回顾性选取2016年4月至2018年6月我院的中晚期乳腺癌患者70例,均于新辅助化疗后实施手术,依据化疗效果分为有效组、无效组,采用免疫组化法检测两组化疗前Ki-67、CDK4表达水平,比较不同Ki-67、CDK4表达水平患者病理完全缓解率(pCR)、2年复发转移情况。结果:有效组Ki-67高表达率、CDK4阳性率高于无效组(P<0.05);Ki-67高表达患者pCR率高于Ki-67低表达者,CDK4高表达者pCR率高于CDK4低表达者(P<0.05);Kaplan-Meier曲线显示,Ki-67低表达的乳腺癌患者2年复发转移率低于Ki-67高表达者(P<0.05),CDK4高表达的乳腺癌患者2年复发转移率与CDK4低表达者无明显差异(P>0.05);Spearman相关分析显示,乳腺癌患者Ki-67、CDK4表达变化与化疗效果呈正相关(r=0.569、0.481,P<0.05)。结论:Ki-67、CDK4高表达的乳腺癌患者经NACT后获得pCR率更高,化疗疗效更优,但Ki-67高表达者预后较差,CDK4表达情况与预后相关性不大。     

MCM7和Ki-67在乳腺癌中的表达及其与新辅助化疗关系的研究

目的探讨乳腺癌新辅助化疗前后MCM7和Ki-67蛋白的表达状况,分析其与化疗疗效的关系。方法采用免疫组化方法检测55例乳腺癌新辅助化疗前后标本中MCM7和Ki-67的表达。结果新辅助化疗有效率为76.4%。化疗前MCM7和Ki-67蛋白阳性表达均显著高于化疗后（P〈0.01）;化疗前MCM7蛋白阳性表达显著高于Ki-67（P〈0.01）。化疗有效组（42例）MCM7蛋白阳性表达显著高于无效组（13例）（P〈0.01）,而Ki-67蛋白表达差异无统计学意义（P〉0.05）。化疗前MCM7、Ki-67表达呈正相关（r=0.58,P〈0.01）。结论ET方案新辅助化疗有较好的疗效,可能通过抑制MCM7、Ki-67蛋白的表达阻止乳腺癌细胞的增殖。MCM7蛋白高表达者化疗更敏感,MCM7可作为临床指导乳腺癌化疗并预测化疗敏感性的分子生物学指标之一。     

局部进展期乳腺癌新辅助化疗前后生物标志物表达变化与疗效的相关性

目的：探讨局部进展期乳腺癌行新辅助化疗前后相关生物标志物的表达变化情况与化疗疗效的相关性。方法：采用免疫组化方法检测102例新辅助化疗前后局部进展期乳腺癌组织中雌激素受体（ER）、孕激素受体（PR）、人类表皮生长因子受体－2（HER －2）、p53和增殖细胞核抗原（Ki －67）等表达,分析化疗前后生物标志物表达变化与化疗疗效的相关性。结果：ER 阴性组、PR 阴性组、Ki －67高表达组的新辅助化疗有效率分别为50．0％、49．1％、51．4％,高于 ER 阳性组26．0％、PR 阳性组25．5％、Ki －67低表达组9．4％（P ＜0．05）。Logistic 多因素回归分析显示,ER、Ki －67的表达水平是评估化疗疗效的独立因素（P ＜0．05）。Luminal 型乳腺癌总生存期高于 non －Luminal 型（Long －rank 检验,P ＜0．05）。结论：ER、Ki －67、分子亚型可作为局部进展期乳腺癌新辅助化疗疗效判断的重要预测指标。     

Relationship of clinical and pathologic response to neoadjuvant chemotherapy and outcome of locally advanced breast cancer

BACKGROUND AND OBJECTIVES: Neoadjuvant chemotherapy in locally advanced breast cancers produces histologically evaluable changes and frequently reduces the size of the primary tumor. Local clinical response to neoadjuvant chemotherapy may correlate with response of distant metastases. Therefore, clinical or pathological factors, which predict or assess response to treatment, may predict outcome after consideration for initial extent of disease. METHODS: To identify pretreatment characteristics of locally advanced breast cancers which predict clinical and pathologic response to neoadjuvant chemotherapy as well as survival and to assess the utility of postoperative histologic changes, we retrospectively studied one hundred forty-four patients with locally advanced breast cancer treated with neoadjuvant chemotherapy between January 1975 and July 1996. Patients were identified through pathology records of the Mount Sinai Medical Center and via one of the author's clinical databases. Pathologic and clinical responses to neoadjuvant chemotherapy were correlated with survival. Stepwise logistic regression was used to identify variables most significantly related to clinical response and pathologic axillary lymph node involvement. RESULTS: Complete clinical response with no palpable tumor was noted in 7/86 patients (8%) and complete pathologic response was achieved in 18/138 patients (13%). Both clinical (P = 0.038) and pathologic response (P = 0.011) were related to tumor size at the time of diagnosis: smaller tumors were more likely to respond to chemotherapy than larger tumors. Histologic evidence of chemotherapeutic effect, i.e., cytoplasmic vacuolization, change in the number of mitoses and localized fibrosis in lymph nodes did not correlate with clinical or pathologically measured response. Clinical and pathologic response was not associated with age, histology, differentiation, or type of chemotherapy. No residual tumor was found in the axillary nodes of 27% (37) of the patients. Age and complete pathologic response were the only variables significantly related to pathologic nodal status. Eighty-four percent of the 61 patients under 50 years of age had nodal involvement compared to 65% of older patients (P = 0.014). Fifty percent of complete pathologic responders had positive axillary lymph nodes compared to 76% of patients who did not have a complete pathologic response (P = 0.020). Distant disease-free (P = 0.039) and overall survival (P = 0.035) were related to the number of involved axillary lymph nodes. After consideration for pathologic lymph node status, no other variable was significantly related to distant disease-free or overall survival in multivariate analysis. No variable was significantly related to local disease-free survival. Age, clinical tumor size, clinical lymph node status, clinical response, type of chemotherapy, histology, differentiation, chemotherapy effects on primary tumor and lymph nodes, decline in the number of mitoses, and degree of fibrosis in nodes were not predictive of distant recurrence or overall survival. CONCLUSIONS: This study of patients treated with neoadjuvant chemotherapy for locally advanced breast cancers found little evidence that measurable clinical or pathologic changes attributable to chemotherapy predicted survival. Axillary lymph node status, associated with young age, was the most important prognostic indicator in these patients.