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.     

Response of Triple Negative Breast Cancer to Neoadjuvant Chemotherapy: Correlation between Ki-67 Expression and Pathological Response

Triple-negative breast cancers constitute about 15% of all cases, but despite their higher response to neoadjuvant chemotherapy, the tumors are very aggressive and associated with a poor prognosis as well as a higher risk of early recurrence. This study was retrospectively performed on 101 patients with stage II and III invasive breast cancer who received 6–8 cycles of neo-adjuvant chemotherapy. Out of the total, 23 were in the triple negative breast cancer subgroup. Nuclear Ki-67 expression in both the large cohort group (n=101) and triple negative breast cancer subgroup (n=23) and its relation to the pathological response were evaluated. The purpose of the study was to identify the predictive value of nuclear protein Ki-67 expression among patients with invasive breast cancers, involving the triple negative breast cancer subgroup, treated with neoadjuvant chemotherapy in correlation to the rate of pathological complete response. The proliferation marker Ki-67 expression was highest in the triple negative breast cancer subgroup. No appreciable difference in the rate of Ki-67 expression in triple negative breast cancer subgroup using either a cutoff of 14% or 35%. Triple negative breast cancer subgroup showed lower rates of pathological complete response. Achievement of pathological complete response was significantly correlated with smaller tumor size and higher Ki-67 expression. The majority of triple negative breast cancer cases achieved pathological partial response. The study concluded that Ki-67 is a useful tool to predict chemosensitivity in the setting of neoadjuvant chemotherapy for invasive breast cancer but not for the triple negative breast cancer subgroup.     

Impact of neoadjuvant chemotherapy on Ki-67 and PCNA labeling indices for esophageal squamous cell carcinomas

PURPOSE: The effects of neoadjuvant chemotherapy (CT) on Ki-67 and proliferating cell nuclear antigen (PCNA) labeling index (LI) were analyzed, using biopsy and surgical specimens of esophageal cancer. METHOD AND MATERIALS: Immunohistochemical staining for Ki-67 and PCNA was performed for biopsy and surgical specimens of 35 patients with esophageal squamous cell carcinoma. Seventeen patients were treated with neoadjuvant CT (CT group), while no preoperative treatment was performed for the remaining 18 patients (control group). As neoadjuvant CT, cisplatin of 50 mg/body/week was administered 2-5 times (100-250 mg in total) until 7-10 days before subtotal esophagectomy. RESULT: Significant correlation between the LIs of biopsy and surgical specimens was observed for the control group (p = 0.006 for Ki-67 and p = 0.005 for PCNA), although both LIs of surgical specimens were significantly higher than those of biopsy specimens (p < 0.05). However, no significant correlation between LIs of biopsy specimens and those of surgical specimens was observed for the CT group. In addition, the LIs of the surgical specimens of the CT group were significantly lower than the LIs of the control group (p < 0.005 for Ki-67 and p < 0.05 for PCNA). Significant decrease in Ki-67 LI after neoadjuvant CT was noted especially for well or moderately differentiated squamous cell carcinomas and/or tumors treated with high-dose cisplatin (150-250 mg). CONCLUSION: Significant correlation of Ki-67 and PCNA LIs between biopsy and surgical specimens was demonstrated for the control group. Neoadjuvant CT decreased the percentage of cycling and proliferative tumor cells of esophageal cancer.     

Bcl-2 expression on fine-needle aspirates from primary breast carcinoma: correlation with other biologic factors.

BACKGROUND: The bcl-2 gene encodes for a protein that is involved in cell death regulation. It frequently is expressed in breast tumors, in which it is associated with favorable prognostic factors. It has been suggested that bcl-2 also may act as a modulator of response to chemotherapy and/or endocrine therapy. Because fine-needle aspiration (FNA) biopsy has been established as a reliable method for the diagnosis and biologic characterization of breast carcinoma, we assessed Bcl-2 expression on FNAs from primary breast carcinoma and evaluated its correlations with other prognostic variables. METHODS: Bcl-2, estrogen receptor (ER), progesterone receptor (PgR), p53 protein expression, and Ki-67 growth fraction were evaluated by immunocytochemistry on FNAs from 130 patients with primary breast carcinoma. Nuclear cytologic grade was assessed on FNA smears. RESULTS: Bcl-2 was expressed in 99 of 130 FNAs (76%). Bcl-2 expression was correlated with positive ER (P < 0.001) and PgR (P < 0.001) status and inversely correlated with p53 (P = 0.0036), Ki-67 (P = 0.0073), and nuclear cytologic grade (P < 0.001). CONCLUSIONS: Bcl-2 expression, evaluated by immunocytochemistry on FNAs from primary breast carcinoma, correlates with favorable prognostic features such as ER and PgR expression, p53 negativity, a low Ki-67 index, and high tumor differentiation. These results are in agreement with those found on histologic samples. As FNA biopsy is used increasingly as a primary tool in the diagnosis of breast carcinoma, Bcl-2 evaluation by immunocytochemistry on FNA may provide, in addition to other biologic variables, useful information for prognostic and predictive purposes, particularly in patients considered to be candidates for neoadjuvant treatments. Cancer (Cancer Cytopathol) Copyright 1999 American Cancer Society.     

新辅助化疗对乳腺癌疗效和雌激素受体孕激素受体Ki-67和人表皮生长因子受体2表达的影响分析

目的了解新辅助化疗（NAC）在局部进展期乳腺癌治疗前后ER、PR、Ki-67及HER-2的变化,探讨其与新辅助化疗疗效之间的相关关系。方法 46例接受新辅助化疗的乳腺癌患者纳入研究,分析患者术前弹射式空芯针穿刺活检标本和术后大标本癌组织ER、PR、Ki-67和HER-2表达的变化。患者化疗前行乳腺肿瘤粗针穿刺活检并免疫组化方法检测肿瘤组织ER、PR、Ki-67和HER-2的表达。化疗后评估疗效并对接受手术的患者的手术标本通过同法检测各指标的表达。结果新辅助化疗前后ER、PR、Ki-67和HER-2的表达均发生了改变,新辅助化疗前ER、PR、Ki-67和HER-2阳性表达的肿瘤组织新辅助化疗后下调（ER：82.6%和80.4%;PR：78.3%和71.7%;Ki-67：39.1%和30.4%;HER-2：28.3%和26.1%）,但没有统计学意义（P〉0.05）。ER、PR、Ki-67和HER-2阳性表达疗效有效率与阴性表达有效率分别为ER：68.4%和50.0%;PR：66.7%和60.0%;Ki-67：77.8%和57.1%;HER-2：53.8%和69.7%。ER、PR、Ki-67、HER-2表达状态与化疗效果均无明显的关系（均P〉0.05）。结论新辅助化疗可以改变ER、PR、Ki-67和HER-2的表达,本临床研究未发现ER、PR、Ki-67和HER-2的变化与局部进展期乳腺癌的新辅助化疗疗效有相关关系。     

Analysis of hormone receptors and proliferation fraction in fine-needle aspirates from primary breast carcinomas during chemotherapy or tamoxifen treatment.

Twelve postmenopausal women (54-93 years) with primary breast carcinoma were treated with tamoxifen due to infirmity or refusal to undergo surgery. Seven premenopausal patients (32-50 years) were given preoperative chemotherapy because of large tumors or inflammatory carcinoma. Fine-needle aspiration biopsy was used to procure tumor cells for diagnosis, hormone receptor determination and analysis of proliferation fraction. Aspirations were repeated every 3 months in the tamoxifen group and each month in patients receiving chemotherapy. Two patients who responded to tamoxifen had tumors with more than 75% estrogen receptor positive cells. A decreased proliferation fraction was observed in two tumors responding to tamoxifen. Eight patients, all with estrogen receptor positive tumors, had stable disease. Progressive disease was observed in two patients with less than 25% receptor positive cells. In these tumors the percentage of proliferating cells remained high during therapy. Objective response was recorded for six patients treated with chemotherapy. The clinical response was reflected in a decreased proliferation fraction. No correlation was observed between response and percentage of proliferating cells in the untreated tumor. The results suggest that analysis of tumor cell characteristics such as hormone receptor content and proliferation fraction can be used to predict and monitor response to endocrine treatment and chemotherapy in breast carcinomas.     

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.     

The effect of chemotherapy on Ki-67, Bcl-2 and Bak expression in primary tumors and lymph node metastases of breast cancer

The aim of this study was the analysis of Ki-67, Bcl-2 and Bak expression in primary tumor and axillary lymph node metastases of breast cancer as well as an attempt to assess preoperative chemotherapy influence on the mentioned markers with regard to changes in the morphological appearance of the primary tumor and its metastases. Immunohistochemical examinations of Ki-67, Bcl-2 and Bak expression were conducted on sections collected from 135 patients treated surgically on invasive ductal breast cancer. Sixty-four of these patients were administered preoperative chemotherapy, whilst on 71 patients the surgery was performed without initial chemotherapy. In the group of patients without preoperative chemotherapy positive correlation in Ki-67 and Bcl-2 expression between primary tumors and lymph node metastases (p<0.0001, r=0.707; p<0.0001, r=0.604, respectively) was observed. In the group of patients after chemotherapy positive correlation between primary tumors and lymph node metastases in case of Bcl-2 and Bak proteins (p<0.04, r=0.424; p<0.02, r=0.478, respectively) was observed. It was also found that preoperative chemotherapy has an influence on the expression of proteins connected with proliferation and apoptosis and thus, it can influence neoplastic process biology. It does not have any significant impact on the proapoptotic Bak protein expression either in primary tumor or in lymph node metastases of breast cancer. However, it is related to lower expression of antiapoptotic Bcl-2 protein (p<0.0005) and of Ki-67 proliferation marker (p<0.03) in primary tumors, which indirectly indicates a beneficial influence of preoperative chemotherapy on the primary tumor. Concurrently, the influence of neoadjuvant therapy on lymph node metastases seems to be relatively small, which can limit its effectiveness.     

HER-2/neu expression as a predictor of response to neoadjuvant docetaxel in patients with operable breast carcinoma

BACKGROUND: The use of biologic markers to predict response to neoadjuvant chemotherapy may permit tailoring regimens to achieve maximal tumor response. Taxanes have demonstrated excellent activity in breast carcinoma; however, tumor-specific factors that predict clinical response have not been characterized thoroughly. METHODS: The authors performed a historic review evaluating the association of tumor prognostic factors and response to neoadjuvant cyclophosphamide and doxorubicin (AC) with or without docetaxel (D) (AC vs. AC+D) in 121 women who previously were enrolled in a Phase III, randomized, clinical trial. Using pretreatment biopsy materials, immunohistochemical studies were performed for estrogen receptor (ER), progesterone receptor (PR), HER-2/neu, p53, and Ki-67. Outcome variables were pathologic complete response (pCR) and positive clinical response (cPOS), which was defined as a >/= 50% regression in clinical tumor size prior to surgery. RESULTS: In a multivariate analysis that controlled for tumor size and lymph node status, improved cPOS rates were observed with the addition of docetaxel in women with HER-2/neu-negative tumors (81% vs. 51%; P < 0.05), yielding an adjusted odds ratio of 3.5 (95% confidence interval, 1.2-13.0) in favor of docetaxel. Women who had HER-2/neu-negative tumors appeared to have a lower response rate with AC alone compared with women who had HER-2/neu-positive tumors (51% vs. 75%; P = 0.06), but response rates were matched when docetaxel was added (81% vs. 78%; P = 0.99). ER, PR, p53, and Ki-67 results were not associated significantly with response rates. CONCLUSIONS: HER-2/neu status may predict improved clinical response rates from the addition of docetaxel to anthracycline-based neoadjuvant chemotherapy. Docetaxel may "rescue" the response in women who have HER-2/neu-negative tumors to match that observed in women who have HER-2/neu-positive tumors treated with AC alone.     

新辅助化疗对乳腺癌患者survivin、Ki-67、ER、C-erbB-2、p53和肿瘤组织学分级的影响及其疗效预测意义

目的探讨新辅助化疗对乳腺癌survivin、Ki-67、ER、C-erbB-2、p53和肿瘤组织学分级的影响,同时研究这些指标对新辅助化疗的疗效预测作用。方法通过免疫组织化学S-P法检测和HE染色对化疗前空芯针穿刺标本和化疗后手术切除的30例乳腺癌组织的survivin、Ki-67、ER、C-erbB-2、p53和肿瘤组织学分级的表达情况。化疗方案为CAF（CTX 600 mg/m^2,THP 50 mg/m2,5-FU500 mg/m^2）和TA（艾素75 mg/m^2,THP 30 mg/m^2）,每3周1疗程,用药2～3个疗程。化疗疗效通过采用临床体检、乳腺彩超检测及术后病理分析综合判断。结果 30例患者中70.0%（21/30）获PR,SD为30.0%（9/30）,全组无恶化病例,总有效率为70.0%（21/30）。通过对化疗前后的指标比较发现：新辅助化疗能降低Ki-67的表达（P〈0.01）和肿瘤分级（P〈0.05）。化疗前后survivin、ER、C-erbB-2和p53表达无明显变化（P〉0.05）。Ki-67高表达（≥20%）、肿瘤分级高的患者和Ki-67低表达（〈20%）、肿瘤分级较低的患者相比,化疗疗效更明显（P〈0.05）。结论新辅助化疗能显著降低乳腺癌组织Ki-67的表达和肿瘤分级,而对survivin、ER、C-erbB-2和p53表达均无显著影响,Ki-67高表达（≥20%）、肿瘤分级高的患者对化疗更敏感、短期疗效更显著。     

肿瘤浸润淋巴细胞比例对乳腺癌新辅助化疗疗效的预测作用

  目的   评价乳腺癌患者行新辅助化疗前穿刺标本中的肿瘤浸润淋巴细胞(tumor infiltrating lymphocytes,TIL)比例与术后病理评估疗效之间的关系。  方法  收集2015年11月至2017年4月156例于天津医科大学肿瘤医院行乳腺肿物穿刺后病理证实为浸润性乳腺癌,并行新辅助化疗及手术的女性患者的临床资料。计算穿刺标本中TIL比例,并分为高、中、低组,利用组织病理学评价标准评估新辅助化疗疗效并分析两者的相关性。  结果  新辅助化疗总有效率为78.2%(122/156),高TIL比例组的新辅助化疗有效率高于低TIL比例组(P < 0.01),激素受体阴性乳腺癌的TIL比例明显高于激素受体阳性乳腺癌(P < 0.01)。新辅助化疗疗效仅与TIL比例相关,与激素受体状态、HER-2受体状态、Ki-67阳性细胞比例无相关性。  结论   乳腺癌穿刺标本中的TIL比例是预测乳腺癌新辅助化疗疗效的独立因子,TIL比例较高的乳腺癌患者的新辅助化疗疗效常更佳。      

新辅助化疗对乳腺癌的组织学分级和生物学指标表达的影响

目的 探讨新辅助化疗对乳腺癌的组织学分级和生物学指标表达的影响.方法 67例接受新辅助化疗的原发性乳腺癌女性患者在化疗前均有核芯针活检结果作为组织学诊断依据,化疗后效果的组织学评估参照日本乳腺癌学会制定的判定标准,分为无效(G1)、轻度有效(G2)、中度有效(G3)、显著有效(G4)和完全有效(G5)5级.采用免疫组化EnVision法对化疗前后的肿瘤组织进行染色,比较化疗前后雌激素受体(ER)、孕激素受体(PR)、人表皮生长因子受体2(Her-2)和Ki-67的表达变化.结果 全组67例患者化疗效果的组织学评估结果显示,G1、G2、G3、G4和G5的患者分别为5例(7.5%)、19例(28.4%)、20例(29.9%)、17例(25.4%)和6例(9.0%).全组有49例患者在化疗前后具有ER、PR、Her-2和Ki-67表达情况的评估结果.化疗后PR阳性率为71.4%,与化疗前(91.8%)相比,差异有统计学意义(P=0.021);而化疗前后ER和Her-2的表达保持稳定.14例浸润性导管癌患者在新辅助化疗后组织学分级发生变化,其中降1级者12例,占85.7%.新辅助化疗后,组织学分级有变化者在G1、G2、G3和G4组中所占的比例分别为0、5.9%、41.2%和54.5%(P=0.013).Ki-67的平均表达率从化疗前的28.3%下降到化疗后的11.0%(P=0.011).化疗后Ki-67的表达率下降＞10%、＞20%、＞30%、＞40%和＞50%者在G1和G2组、G3组、G4和G5组中所占的比例均呈增加趋势,且差异均有统计学意义(均P＜0.05).结论 新辅助化疗后,乳腺癌组织的PR表达显著降低,而ER和Her-2的表达保持稳定;乳腺癌组织的组织学分级和Ki-67的表达也降低,并且好的化疗效果与组织学分级和Ki-67的表达降低相关.     

Ki-67 as a Predictor of Response to Neoadjuvant Chemotherapy in Breast Cancer Patients

Purpose

The objectives of this study were to assess the potential value of Ki-67 in predicting response to neoadjuvant chemotherapy in breast cancer patients and to suggest a reasonable cutoff value for classifying Ki-67 expression.

Methods

This study included 74 breast cancer patients who underwent surgery after anthracycline-based neoadjuvant chemotherapy between 2007 and 2012. We analyzed the clinical and immunohistochemical characteristics using core biopsy specimens obtained before neoadjuvant chemotherapy to determine their correlations with the response to chemotherapy.

Results

A clinical complete response was observed in 6 patients (8.1%); a clinical partial response, in 44 patients (59.5%); and clinical stable disease, in 24 patients (32.4%). A pathologic complete response (pCR) was observed in 10 patients (13.5%). In univariate analysis, estrogen receptor (ER) negativity (p=0.031), human epidermal growth factor receptor 2 (HER2) positivity (p=0.040), and high Ki-67 expression (p=0.036) were predictive factors for a pCR. In multivariate analysis, Ki-67 was the only independent predictor of a pCR (p=0.049). The analysis of Ki-67 values revealed that 25% was a reasonable cutoff value for predicting the response to chemotherapy. In subgroup analysis, a higher Ki-67 value (≥25%) was a significant predictive factor for the response to neoadjuvant chemotherapy, especially in ER-negative and HER2-positive breast cancer patients.

Conclusion

Ki-67 expression in breast cancer tissue may be an effective factor for predicting the response to neoadjuvant chemotherapy. We suggest that a 25% level of Ki-67 expression is a reasonable cutoff value for predicting a response to chemotherapy. Moreover, Ki-67 is a useful predictive factor for pCR, especially in patients with ER-negative and HER2-positive breast cancer.     

Predictive value of Smac, VEGF and Ki-67 in rectal cancer treated with neoadjuvant therapy

The present study aimed to identify whether second mitochondria-derived activator of caspase (Smac), vascular endothelial growth factor (VEGF) and proliferating cell nuclear antigen (Ki-67) expression in pre-treatment tumor biopsies are useful predictive markers of tumor response in patients with rectal cancer undergoing pre-operative chemoradiotherapy (CRT). Paraffin-embedded tissues obtained before and after therapy were evaluated by immunohistochemical staining for Smac, VEGF and Ki-67. The study evaluated the correlation of Smac, VEGF and Ki-67 immunoreactivity in tumor biopsies before treatment of tumor response to pre-operative CRT. Regarding Smac, patients with a favorable response to neoadjuvant CRT had higher pre-therapy levels (p=0.011). The level of Smac expression decreased after neoadjuvant therapy (p=0.044). However, VEGF expression was found to be negatively and significantly correlated with a favorable tumor response to neoadjuvant CRT (p=0.010). A transient increase in VEGF expression was detected in the resected specimens following neoadjuvant therapy (p=0.030). In addition, tumors with a low Ki-67 labeling index (Ki-67-LI) expression were found to be more sensitive to neoadjuvant therapy than those with a high expression of Ki-67-LI (p=0.034). In contrast to VEGF, the Ki-67 expression level decreased after neoadjuvant therapy. Smac, VEGF and Ki-67 expression levels, assessed immunohistochemically from pre-treatment tumor biopsies, may be useful predictive markers of rectal tumor response to pre-operative CRT.     

Alteration of immunohistochemical biomarkers between pre- and post-chemotherapy: hormone receptors,HER2 and Ki-67

The immunohistochemical (IHC) biomarkers of breast cancer, especially hormone receptors and HER2, are very important because the pharmacological therapeutic strategy is generally decided by biomarker expression patterns. Biomarkers are examined on pre-chemotherapeutic biopsy materials from patients in whom neoadjuvant chemotherapy is planned. Statistically significant changes between pre- and post-chemotherapeutic markers have been reported; however, the alterations in biomarkers are poorly understood. Fluctuation of the Ki-67 labeling index (LI) between pre- and post-neoadjuvant therapy is associated with chemotherapeutic effects and with the prognosis of patients. It has been shown that IHC evaluation of Ki-67 LI is useful as a predictive and a prognostic factor. There are issues to be considered surrounding the use of the IHC Ki-67 LI in routine practice, including the standardization of staining procedures and a cutoff point for Ki-67 LI detection. The current understanding of IHC evaluation of biomarkers for breast cancer under neoadjuvant chemotherapy is reviewed based on the literature.     

Decreased tumor cell proliferation as an indicator of the effect of preoperative radiotherapy of rectal cancer

BACKGROUND: Rectal cancer is a common malignancy, with significant local recurrence and death rates. Preoperative radiotherapy and refined surgical technique can improve local control rates and disease-free survival. PURPOSE: To investigate the relationship between the tumor growth fraction in rectal cancer measured with Ki-67 and the outcome, with and without short-term preoperative radiotherapy.Method: Ki-67 (MIB-1) immunohistochemistry was used to measure tumor cell proliferation in the preoperative biopsy and the surgical specimen. MATERIALS: Specimens from 152 patients from the Southeast Swedish Health Care region were included in the Swedish rectal cancer trial 1987-1990. RESULTS: Tumors with low proliferation treated with preoperative radiotherapy had a significantly reduced recurrence rate. The influence on death from rectal cancer was shown only in the univariate analysis. Preoperative radiotherapy of tumors with high proliferation did not significantly improve local control and disease-free survival. The interaction between Ki-67 status and the benefit of radiotherapy was significant for the reduced recurrence rate (p = 0.03), with a trend toward improved disease-free survival (p = 0.08). In the surgery-alone group, Ki-67 staining did not significantly correlate with local recurrence or survival rates. CONCLUSION: Many Ki-67 stained tumor cells in the preoperative biopsy predicts an increased treatment failure rate after preoperative radiotherapy of rectal cancer.     

SUVmax、Ki-67、p53、EGFR对三阴性乳腺癌新辅助化疗疗效的预测价值

目的 探讨18F-FDG PET/CT化疗前SUVmax、Ki-67、p53、EGFR对三阴性乳腺癌（TNBC）及非三阴性乳腺癌（非TNBC）对新辅助化疗完全病理缓解（pathologic complete response, pCR）率的预测价值。方法 初治TNBC患者27例,非TNBC患者184例,在新辅助化疗前行18F-FDG PET/CT显像并测量其SUVmax,取化疗前乳腺肿瘤组织进行Ki-67、p53、EGFR免疫组织化学分析并计算化疗后完全pCR率。结果 TNBC新辅助化疗前的SUVmax明显高于非TNBC的SUVmax（P=0.045）,TNBC新辅助化疗后pCR率明显高于非TNBC（P＜0.001）。在TNBC以及非TNBC中,达到pCR组的化疗前SUVmax与未达到pCR组之间差异无统计学意义（P＞0.05）。Ki-67、p53、EGFR阳性表达组的pCR率与阴性表达组之间差异无统计学意义（P＞0.05）。结论 TNBC对新辅助化疗的敏感度高于非TNBC,且TNBC化疗前SUVmax高于非TNBC,提示TNBC具有较高的能量代谢。化疗前SUVmax以及Ki-67、p53、EGFR不能预测TNBC及非TNBC新辅助化疗的pCR。     

Changes in PgR and Ki-67 in residual tumour and outcome of breast cancer patients treated with neoadjuvant chemotherapy

We collected information on 904 consecutive breast cancer patients treated with neoadjuvant chemotherapy at the European Institute of Oncology, Milan, Italy, between 1999 and 2011. The decrease of PgR and Ki-67 expression after preoperative chemotherapy has a prognostic role in breast cancer patients with residual disease.BackgroundLimited data are available on the prognostic value of changes in the biological features of residual tumours following neoadjuvant therapies in breast cancer patients.Patients and methodsWe collected information through the institutional clinical database on all consecutive breast cancer patients treated with neoadjuvant chemotherapy at the European Institute of Oncology (IEO), Milan, Italy, between 1999 and 2011. We selected patients who did not achieve pathological complete response at final surgery. All patients had a pathological evaluation, including ER, PgR, HER2 protein and Ki-67 expression carried out at the IEO both at diagnostic core biopsy and at final surgery.ResultsWe identified a total of 904 patients. The 5% of patients who were ER positive at diagnostic biopsy had ER-negative residual tumour at final surgery. For PgR expression, 67% of the patients, whose tumours had a PgR >20% at diagnostic biopsy had a PgR <20% at final surgery. The Ki-67 expression changed from >20% to <20% in 40% of the patients. At the multivariate analysis, the decrease of PgR-immunoreactive cells correlated with improved outcome in terms of disease-free survival (DFS) [hazard ratio (HR) 0.73; 95% confidence interval (CI) 0.54–1.00, P 0.046]. In addition, the decrease of Ki-67 expression to <20% of the cells at final surgery was found to be associated with better outcome both in terms of DFS (HR 0.52; 95% CI 0.40–0.68 P < .0001) and overall survival (HR 0.45; 95% CI 0.32–0.64, P < .0001).ConclusionThe decrease of PgR and Ki-67 expression after preoperative chemotherapy has a prognostic role in breast cancer patients with residual disease.     

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。     

乳腺癌新辅助化疗前后Ki-67、HER-2、ER和PR的变化与临床缓解率的关系

目的 比较新辅助化疗前后的乳腺癌患者肿瘤组织中Ki-67、HER-2、ER和PR的改变,探索其变化与临床缓解情况之间的关系。方法 回顾性收集接受新辅助化疗的乳腺癌患者103例,本次观察前均未行任何放疗、化疗和内分泌治疗。化疗前接受14 G空心针刺活检诊断为局部浸润性导管癌或小叶癌。患者经4个周期化疗后94例患者接受手术切除。化疗前后的肿瘤组织采用福尔马林固定,石蜡包埋病理切片法,免疫组化染色法检测化疗前后肿瘤组织中Ki-67、HER-2、ER和PR的变化情况。采用WHO标准评价化疗后的临床缓解率。结果 103例病例经新辅助化疗后有9例发生转移,94例经化疗后进行了手术治疗。术前穿刺和术后肿瘤组织切片染色比较,Ki-67、ER和PR表达发生了明显的改变,而HER-2的前后变化差异不显著。但是,仅Ki-67的表达变化与肿瘤缓解率的关系显著。结论 在乳腺癌的新辅助治疗中,Ki-67的变化可能作为预测新辅助化疗肿瘤缓解率的一个指标,对临床用药和化疗结局有一定的指示作用。