三阳性乳腺癌与Her-2过表达型乳腺癌的预后分析

目的通过探讨三阳性乳腺癌与人表皮生长因子受体2(human epidermal growth factor receptor-2,Her-2)过表达型乳腺癌的临床病理特征及预后的差异,揭示这2种亚型的异质性,以期为这2种乳腺癌诊疗方案的选择提供数据支撑。方法收集2016年7月至2022年9月在徐州医科大学附属医院诊断和收治的三阳性乳腺癌患者179例,Her-2过表达型乳腺癌患者161例,采用病例对照的方法,对其临床资料进行回顾性分析,研究其临床病理特征及预后状况。结果与Her-2过表达型乳腺癌相比,三阳性乳腺癌发病年龄更早,较常发生于绝经前的患者,TNM分期较晚,更容易侵犯脉管和神经,Ki-67(proliferating cell nucleus antigen 67,Ki67)多为高表达;三阳性乳腺癌患者的总生存期(overall survival,OS)与无进展生存期(progression-free survival,PFS)均高于Her-2过表达型。结论三阳性乳腺癌患者的预后优于Her-2过表达型,但由于其靶向治疗与内分泌治疗存在交叉作用,具有耐药性的弊端,需要进一步探究。

Downregulation of wild-type p53 protein by HER-2/neu mediated PI3K pathway activation in human breast cancer cells: its effect on cell proliferation and implication for therapy

Overexpression and activation of HER-2/neu (also known as c-erbB-2), a proto-oncogene, was found in about 30% of human breast cancers, promoting cancer growth and making cancer cells resistant to chemo- and radio-therapy. Wild-type p53 is crucial in regulating cell growth and apoptosis and is found to be mutated or deleted in 60-70% of human cancers. And some cancers with a wild-type p53 do not have normal p53 function, suggesting that it is implicated in a complex process regulated by many factors. In the present study, we showed that the overexpression of HER-2/neu could decrease the amount of wild-type p53 protein via activating PI3K pathway, as well as inducing MDM2 nuclear translocation in MCF7 human breast cancer cells. Blockage of PI3K pathway with its specific inhibitor LY294002 caused Gl-S phase arrest, decreased cell growth rate and increased chemo- and radio-therapeutic sensitivity in MCF7 cells expressing wild-type p53. However, it did not increase the sensitivity to adriamycin in MDA-MB-453 breast cancer cells containing mutant p53. Our study indicates that blocking PI3K pathway activation mediated by HER-2/neu overexpression may be useful in the treatment of breast tumors with HER-2/neu overexpression and wild-type p53.

CORRELATION BETWEEN SERUM HER-2 ONCOPROTEIN AND PATIENTS WITH BREAST CANCER

To detect serum HER-2 oncoprotein levels in patients with operable and metastatic breast cancers, and to study the correlations between serum HER-2 level and lymph node status as well as other clinical parameters. Methods A total of 120 women were studied consisting of 10 healthy volunteers, 31 benign breast disease, 53 operable breast cancer, and 26 metastatic breast cancer patients. The levels of serum HER-2 were measured using an enzyme-liked im-munosorbent assay (ELISA). Results The mean serum HER-2 levels were 9.6 ± 1.5 ng/mL in healthy volunteers, 11.9 ± 1.6 ng/mL in benign breast disease, 13.2 ± 4.2 ng/mL in operable breast cancer, and 30.5 ± 30.8 ng/mL in metastatic breast cancer patients. The former is much lower than the latter three (P = 0.02, 0.001, 0.03, respectively). If using 15 ng/mL as a normal baseline, elevated serum HER-2 levels were observed in none of the healthy volunteers as well as patients with benign disease, but in 18.9% (10/53) operable breast cancer patients and 61.5% (16/26) metastatic patients. In patients with operable breast cancer, there was a positive correlation between serum concentrations of HER-2 and the size of primary tumor (P < 0.05), whereas there was no correlation between serum concentration and axillary lymph node or estrogen receptor status. In patients with metastatic dise-ase, there was no correlation with site of metastases (P > 0.05). Conclusion Serum HER-2 level was strongly correlated with tumor loads and clinical stages, thus acting as a promising predictor of cancer recurrence in breast cancer patients.

GENISTEIN INHIBITS EXPRESSION OF VASCULAR ENDOTHELIAL GROWTH FACTOR IN HER-2/NEU TRANSFECTED HUMAN BREAST CANCER MCF-7 CELLS

Objective： our previous studies have demonstrated that HER-2/neu gene expression in human breast cancer MCF-7 cells promotes angiogenesis in MCF-7 cells xenograft tumors, and genistein inhibits angiogenesis in MCF-7 cells with HER-2/neu expression xenograft tumors. Here, the effects of genistein on the expression of vascular endothelial growth factor （VEGF） in MCR-7 cells with HER-2/neu expression were further studied for exploring the molecular mechanism of anti-angiogenesis in HER-2/neu-overexpressing breast cancer by genistein. Methods： HER-2/neu-overexpressing MCF-7 cells （MCF-7/HER-2） were established by transfecting HEg-2/neu gene into HER-2/neu negative expression breast cancer MCF-7 cells. Immunocytochemical staining, western blot and reverse transcription-polymerase chain reaction （RT-PCR） were adopted to measure the expression of VEGF in MCF-7/HER-2 cells treated by genistein for 24, 48 and 72h. Results： HER-2/neu expression up-regulated VEGF mRNA and protein in MCF-7 cells, genistein decreased VEGF mRNA and protein level in MCF-7/HER-2 cells in a time-dependent manner. Conclusion： These results suggest that VEGF plays an important role in HER-2/neu gene expression promoted antiogenesis in breast cancer and genistein induced down-regulation of the expression of VEGF may be one of the molecular mechanisms of its anti-angiogenesis in HER-2/neu-overexpressing breast cancer.

Comparison of Fluorescence in situ Hybridization and Immunohistochemistry for Assessment of HER-2 Status in Breast Cancer Patients

The accurate assessment ofa proto-oncogene, human epidermal growth factor receptor-2 gene （HER-2）, is extremely important for the therapy and prognosis of breast cancer. Currently, immunohistochemistry （IHC） is the method widely used for the detection of HER-2 protein. Fluorescence in situ hybridization （FISH） has been suggested to be a golden standard assay for HER-2 amplification. This study examined the expression and amplification of HER-2 in paraffin-embedded sections of breast cancer tissues, and compared the two methods on the measurement of HER-2 status. HER-2 gene and protein were determined in breast cancer samples from 52 Chinese women by FISH and IHC respectively. The findings indicated that the HER-2 gene amplification was found in 18 cases （34.6%） by FISH and the HER-2 protein over-expression （score 3＋） in 15 cases （28.8%） by IHC. hnmunohistochemically, 28.6% of the cases scored as 2＋ and 93.3% of the cases scored as 3＋ were HER-2-positive by FISH. There was a significant correlation between the HER-2 gene amplification and HER-2 protein over-expression in breast cancer （P〈0.005）. No correlation was noted between the HER-2 gene amplification and any of the clinicopathological parameters examined, including age, menopausal status, menarche age, tumor size, histological tumor type, histological grade, lymph node status, and the expression of ER and PR. It was concluded that the detection of HER-2 gene amplification in breast cancer by FISH is valuable and can compare with HER-2 protein detection by IHC.

HER-2 expression after neoadjuvant chemotherapy of the breast cancers

Objective:The aim of this study was to study changes of HER-2 expression after neoadjuvant chemotherapy in the breast cancer cases.Methods:One hundred and thirty-seven female patients with primary breast cancers,who received neoadjuvant chemotherapy,underwent core needle puncture and Mammotome biopsy before chemotherapy,and the biopsy results were used as the basis of histological diagnosis,fluorescence in situ hybridization (FISH) was performed to test HER2 status of tumor tissues before and after chemotherapy.All patients underwent FEC,TE,or AC neoadjuvant chemotherapy of 2-6 cycles before surgery.Results:Twenty-two patients were positive according to FISH test among 137 preoperative patients,8 patients achieved pathological complete remission after chemotherapy (three HER-2 positive patients and five negative patients),91 patients achieved partial remission,24 patients were stable,and 14 cases were invalid.Twenty-two patients were positive according to FISH test (8 patients with pathological complete remission did not undergo test),and positive patients still expressed positively after chemotherapy before neoadjuvant chemotherapy.Three negative patients were converted to be positive,and changes before and after chemotherapy had no statistical difference (P>0.05).Conclusion:Neoadjuvant chemotherapy makes no influence on patients with HER-2 positive expression,while patients with negative expression can be converted to be positive,but without significant difference.

HER-2,P53 and Hormonal Receptors Protein Expression as Predictive Factors in Breast Cancer Prognosis

OBJECTIVE Breast cancer is a heterogeneous disease with vari-able biological and clinical characteristics.We conducted a studyto evaluate P53,HER-2/neu and hormonal receptor expression aspredictors of prognosis in breast cancer.METHODS In a prospective study,we recruited 81 consecutivepatients with primary operable breast cancer who were treatedwith mastectomy followed by locoregional radiotherapy or che-motherapy and studied the presence of P53,HER-2/neu andhormonal receptors (ER/PR) expression in tumor tissues by im-munohistochemical staining.Associations between these markersexpression and clinical outcomes,including local and regionalrecurrence and metastasis were evaluated.Statistical analysis wasperformed with the SPSS software.RESULTS The mean time of follow-up was (47.3±4.6) months.Expression of P53,HER-2/neu,Estrogen receptors and progester-one receptors were observed in 31.1%,38.5%,31.8% and 51.7% ofthe patients,respectively.P53,HER-2/neu and Negative ER statuswere potent predictors of local-regional recurrence (P=0.034,0.038,0.044,respectively).Also HER-2/neu,Negative ER and NegativePR status were strong predictors of metastasis (P=0.001,0.042,0.054,respectively).CONCLUSION P53 and HER-2/neu expression and also steroidreceptors status (ER/PR status) have an important role in predict-ing the outcome of breast cancer and thus may be of value in se-lecting suitable therapeutic strategy and determining prognosis inthese patients.

Research of vitamin E succinate combined with paclitaxel on the apoptosis of Her-2 over-expressing breast cancer cells

Objective： The aim of this study was to detect apoptosis rates of Her-2 overexpression breast cancer cells, which were administrated with vitamin E succinate （VES） combined with paclitaxel at different dosages, or administrated alone; to discuss the mechanism of their actions. Methods： Using immunohistochemical method to detect Her-2 expression of MDA- MB-453 cells. Using TUNEL assay to detect apoptosis rates of MDA-MB-453 ceils, with the concentrations at 10, 20 mg/L of VES and 50, 100 nmol/L of paclitaxel, and also combined together for 24 or 48 h. Then compared apoptosis action of various combinations. Results： The expression rate of 95% Her-2 was interval （63.32%, 69.60%）; VES and paclitaxel both induced apoptosis of MDA-MB-453 cells, and it is dose to time dependence. It was strongest in apoptosis at 10 mg/L VES and 100 nmol/L paclitaxel in MDA-MB-453 cells 48 h later. Conclusion： VES and paclitaxel both induced apoptosis of MDA-MB-453 cells. It is stronger when the two drugs are administrated together. The mechanism is probably related to reduction of bcl-2 expression, so as to be more sensitive to paclitaxel. Synergistic effect is also possible for the two drugs influence tumor cells in different growing phases.

Impressive Objective Response to Nab-Paclitaxel plus Trastuzumab as Fifth Line Therapy in an Elderly HER-2 Positive Breast Cancer Patient

Background: Agent targeting HER-2 pathway plus chemotherapy has represented a major progress in the management of patients with breast cancer. However, the role of late-line treatment in heavily pretreated patients is still largely unclear. In the last decade, nab-paclitaxel has shown significant activity and good toxicity profile in metastatic breast cancer. Case Presentation: We report the case of a 76-year-old Caucasian woman with metastatic HER-2 positive ductal infiltrating breast carcinoma treated with a combination of weekly nab-paclitaxel and trastuzumab as fifth-line therapy. She had previously received first-line paclitaxel and trastuzumab, second-line vinorelbine and trastuzumab, third-line TDM1 and fourth-line oral capecitabine and lapatinib. Clinical and radiological staging showed progression at bone, skin and soft-tissue. The patient received weekly nab-paclitaxel plus trastuzumab. Massive objective response was clinically and PET documented which lasted 8 months. Tolerance to treatment was fairly good as well as cardiac safety. Conclusion: To the best of our knowledge, this is the first reported case of efficacy of nab-paclitaxel in combination with trastuzumab as fifth-line of treatment in a patient with metastatic HER-2 positive breast cancer.

Relationship between expression of ER, PR, Her-2, Ki-67 and neoadjuvant chemotherapy effect in breast cancer

Objective: The purpose of the study was to investigate the relationship between the expression of estrogen receptor(ER), progestogen receptor(PR), human epidermal growth factor receptor(Her-2), Ki-67 and the effect of neoadjuvant chemotherapy in breast cancer. Methods: The expression of ER, PR, Her-2 and Ki-67 in 45 breast cancers which received neoadjuvant chemotherapy was detected by immunohistochemistry. Results: The effective rates in ER negative and PR negative groups were higher than those in ER positive and PR positive groups(83.3% vs 59. 4%, 82.4% vs 60.6%). There was no significant difference of the effective rate between Her-2 overexpressed group and Her-2 non-overexpressed group(81.8% vs 64.1%), and the same thing happened between Ki-67 negative group and Ki-67 positive group(67.7% vs 63.2%). Conclusion: In the patients with breast cancer, ER, PR negative ones were more sensitive to neoadjuvant chemotherapy. These patients may get more benefits from chemotherapy. ER, PR could be feasible markers for predicting the effective rate of neoadjuvant chemotherapy.

Detection of HER-2/neu Amplification on Fine Needle Aspirates of Breast Cancer Using Fluorescence in Situ Hybridization

The accuracy of diagnostic assays for HER-2/neu in breast cancer is extremely important as HER-2/neu status is essential in tailoring adjuvant and/or neoadjuvant treatment in every patient. FNAC is widely practiced in Egypt in preoperative diagnosis of breast cancer for its low cost and high diagnostic accuracy. Since the determination of HER-2/neu protein expression on cytological preparations was previously found to be unreliable for clinical use, we opted for the assessment of HER-2/neu status in fine needle aspirates using FISH. The main objective of this study was to evaluate the reliability of HER-2/neu status assessment by FISH on fine needle aspirates of breast cancers by comparing the results with IHC and FISH on FFPE tissue sections obtained from corresponding surgically resected specimens. Fine needle aspirates from 40 breast cancer patients with pathologically confirmed breast cancer were included in the study. They were submitted for HER-2/neu evaluation by FISH. After surgery, the corresponding FFPE sections were evaluated for HER-2/neu by FISH and by IHC. FNAs from 11 cases proved to be amplified by FISH, while 29 cases were not amplified. Apart from two cases that showed lack of signals, all specimens evaluated by FISH on the corresponding FFPE sections showed matched results. The Measurement of Agreement between FISH on FNAs and FISH on FFPE sections was 86.7%, while that between FISH on FNAs and IHC was 72.5%. The high concordance rate in the present study between FISH evaluation of HER-2/neu gene amplification on FNAC samples and their corresponding FFPE samples indicate that FISH may be a reliable technique for HER-2/neu assessment on FNAs. Furthermore, FISH on FNAs gave us better hybridization signals than their corresponding FFPE tissue sections. Finally, we also conclude that all score (2+) cases by IHC should be reevaluated by FISH which is crucial for the patient management.

Evaluation of Tobacco Use and Her-2 Receptor Expression in Breast Cancer in an Ethnically Diverse Inner-City Population

Background: Tobacco is linked to most cancers however despite overwhelming biological plausibility and decades of epidemiological studies, no association has been established between tobacco and breast cancer. Although estrogen receptor status has been looked at as a variable there has been no evaluation of the role of Her-2 and smoking in breast cancer. Methods: Review of records from patients treated at the University of Miami/Jackson Memorial Hospital from 1998-2012. The incidence of smoking and Her-2 expression in1255 women was evaluated. Data was analyzed by age, race, ethnic group, menopausal status, tumor stage, and ER/PR/Her-2 receptor status. Results: 1255 charts were analyzed with 1094 having full information. Overall rate of Her-2 expression 18.1%. The rate of Her-2 expression was 21.4% in smokers and 17.0% in non-smokers (p = 0.10). The rate of Her-2 expression was 10.8% in Caucasian smokers and 9.8% in Caucasian non-smokers (p = 0.88);24.5% in smokers of African descent and 17.3% in non-smokers of African descent (p = 0.24);22.9% in Latino smokers and 17.4% in Latino non-smokers (p = 0.10). The rate of Her-2/ER expression was 9.4% in smokers and 7.9% in non-smokers (p = 0.42);5.4% in Caucasian smokers and 4.9% in Caucasian non-smokers (p = 0.916);12.2% in smokers of African descent and 5.9% in non-smokers of African descent (p = 0.11);9.5% in Latin smokers and 8.8% in Latin non-smokers (p = 0.77). Conclusions: We found non-statistically significant positive associations in all analyses between Her-2 expression with or without ER expression and tobacco exposure when analyzed by ethnicity.

Chidamide Combined with Paclitaxel Liposome for the Treatment of Advanced HER2-negative Breast Cancer in Clinical Study

The purpose of this study was to investigate the efficacy and safety of chidamide combined with paclitaxel liposome in the treatment of advanced HER-2-negative breast cancer.First,41 patients with advanced HER-2-negative breast cancer who had received two chemotherapy regimens from May 2017 to November 2017 were randomly selected to receive chidamide combined with paclitaxel liposome treatment(observation group,n=20)or placebo combined with paclitaxel liposome treatment(control group,n=21).The treatment scheme of the observation group was oral chidamide 30mg twice a week for 2 months.In addition,on day 1,the patients were given paclitaxel liposome orally and intravenously administered with 175 mg/m2 for 1 cycle for 21 days and 3 cycles of chemotherapy.The treatment scheme of the control group was oral placebo 30 mg twice a week for 2 months.In addition,the method of paclitaxel liposome administration was the same as the observation group.The response rate(RR),disease control rate(DCR),and progression-free survival(PFS)were compared between the two groups.The results showed that all the 41 patients could be evaluated.In the observation group,CR5,PR7,SD5 and PD3 were obtained.RR was 60.0%and DCR was 85.0%.In the control group,CR3,PR3,SD5 and PD10 were obtained.RR was 28.6%and DCR was 52.4%.RR and DCR in the observation group were better than those in the control group,and the difference was statistically significant(P<0.05).The median PFS of the observation group was 5.2 months,longer than that of the control group(3.1 months,P<0.05).The main adverse reactions in the two groups were gastrointestinal reactions and bone marrow suppression,with grade 1~2 as the main ones.The incidence of leukopenia,thrombocytopenia and nausea and vomiting in the observation group was higher than that in the control group(P<0.05).Therefore,the chidamide combined with paclitaxel liposome is effective in the treatment of advanced HER-2-negative breast cancer,and the adverse reactions can be tolerated.

赫赛汀治疗Her-2阳性乳腺癌56例疗效和毒性观察

目的:观察赫赛汀(Herceptin)治疗人类表皮生长因子受体2(Her-2)过度表达晚期乳腺癌的临床疗效。方法:将56例Her-2过度表达的晚期乳腺癌患者随机分成3组,其中组1为赫赛汀单药组(n=18),首次剂量为赫赛汀4 mg/kg静脉注射,以后改为每周2 mg/kg静脉注射,维持1年;组2(n=20)为联合化疗组,联合多西他赛75 mg/m2,每3周给药1次,维持至治疗结束。赫赛汀的用法为4 mg/kg静脉注射,共联合化疗治疗4次,4周期化疗结束后,每月维持治疗剂量4 mg/kg静脉注射,共4次;组3(n=18)为对照组给予常规化疗药物治疗。结果:1、2两组使用赫赛汀治疗的乳腺癌患者客观缓解率(RR)分别为50.0%和83.3%,肿瘤进展时间(TTP)分别为5.8个月和10.4个月,两个用药组临床疗效与对照组相比差异有统计学意义(P<0.05)。结论:赫赛汀单药和联合化疗治疗Her-2过度表达的晚期乳腺癌均有较好的临床疗效,其中赫赛汀联合化疗治疗乳腺癌效果更显著。

曲妥珠单抗联合多西紫杉醇治疗Her-2/neu高表达转移性乳腺癌的疗效和不良反应

背景与目的:大约有20%～30%的乳腺癌患者Her-2/neu高表达,Her-2/neu高表达与患者的不良预后密切相关。化疗药物联合曲妥珠单抗可以显著提高Her-2/neu高表达乳腺癌患者的化疗有效率和生存率,多西紫杉醇是近年来治疗乳腺癌有效的化疗药物之一。本研究旨在观察曲妥珠单抗联合多西紫杉醇治疗Her-2/neu高表达转移性乳腺癌的疗效与不良反应。方法:22例Her-2/neu高表达转移性乳腺癌患者接受曲妥珠单抗联合多西紫杉醇方案治疗,曲妥珠单抗的首次剂量为8mg/kg,以后的剂量为6mg/kg。多西紫杉醇75mg/m2,每21d重复一次。按WHO疗效评价标准评价疗效,按WHO化疗药物急性和亚急性不良反应评价标准评价不良反应。结果:全组22例患者共完成96个周期化疗(中位数3周期,范围2～6周期),所有患者均可评价疗效。22例患者中完全缓解2例,部分缓解12例,病情稳定4例,病情进展4例,客观有效率(CR+PR)63.64%,中位疾病进展时间5.4个月,1年生存率59%。全组患者均可评价不良反应,主要不良反应为骨髓抑制,其中Ⅲ～Ⅳ度白细胞减少发生率为54.5%,部分患者有发热(第一次输注曲妥珠单抗时出现)和轻度的心肌劳损。结论:曲妥珠单抗联合多西紫杉醇方案治疗Her-2/neu高表达转移性乳腺癌近期疗效较高,不良反应轻,患者可以耐受。

三阴性乳腺癌和HER-2过表达乳腺癌的临床病理特征比较

目的探讨三阴性乳腺癌和HER-2过表达乳腺癌的临床病理特征。方法选取210例雌、孕激素受体均为阴性的乳腺癌患者为研究对象，根据HER-2检测结果将其分为两组，三阴性乳腺癌组（Estrogen Receptor ER、Progesterone Receptor PR和HER-2表达阴性）85例，HER-2过表达乳腺癌组（ER、PR阴性和HER-2表达阳性）125例，比较两组发病部位、病理类型、肿瘤直径大小、淋巴结转移、组织学分级、TNM分期、p53表达及Ki-67表达情况。结果两组在发病部位上差异无统计学意义（P=0．4317），均好发于外上象限部位，分别占58．82％和46．4％；两组在病理类型、肿瘤直径大小、TNM分期、p53表达上差异无统计学意义（P=0．6146、P=-0．2744、P=0．5909、P=0．6002），其中浸润性导管癌、直径为2-5cm、II期所占比例均最高；三阴性乳腺癌组淋巴结转移以阳性为主，占56．47％，HER-2过表达乳腺癌组以阴性为主，占67．2％，差异有统计学意义（P=．0007）；两组在组织学分级上，差异有统计学差异（P=0．0278），其中组织学2级所占比例最高；三阴性乳腺癌组在Ki-67表达上与HER-2过表达组相比，有差异有统计学差异（P=0．0041）。结论三阴性乳腺癌和HER-2过表达乳腺癌的病理类型均好发在外上象限，以浸润性导管癌为主，就诊时均是II期病人为主。三阴性乳腺癌较HER-2过表达乳腺癌的侵袭性更强，细胞增殖更活跃，组织学分级更高，更易发生淋巴结转移，因此预后更差。

曲妥珠单抗联合TC方案治疗HER-2过度表达乳腺癌的效果及安全性

目的探讨曲妥珠单抗联合多西他赛、环磷酰胺化疗方案(TC)治疗人类表皮生长因子受体2(HER-2)过度表达乳腺癌的效果和安全性。方法选取2015年10月~2016年10月于新疆医科大学附属肿瘤医院就诊的79例乳腺癌患者作为研究对象,采用随机数字表法分为研究组与对照组,其中研究组38例,对照组41例。对照组患者在乳腺癌根治术前采用TC联合化疗,研究组在对照组基础上采用曲妥珠单抗治疗。治疗18周后,比较两组患者的治疗效果、不良反应发生率,比较两组治疗前后HER-2蛋白、B7同源体(B7-H1)及白细胞介素-2(IL-2)表达情况。结果治疗后研究组的总有效率显著高于对照组(P<0.05);治疗后两组HER-2过表达率均显著降低(P<0.05),且研究组治疗后HER-2过表达率显著低于对照组(P<0.05);研究组治疗后B7-H1、IL-2阳性表达率均较治疗前显著降低(P<0.05);两组患者治疗后不良反应发生率差异无统计学意义(P>0.05)。结论曲妥珠单抗联合TC方案可有效降低HER-2过度表达乳腺癌患者的HER-2蛋白、B7-H1和IL-2表达含量,提高临床治疗效果,且不会增加用药风险。

曲妥珠单抗联合紫杉醇诱导过表达HER-2的乳腺癌裸鼠皮下移植瘤乳腺癌细胞凋亡的作用机制和效果研究

目的探讨曲妥珠单抗联合紫杉醇诱导过表达表皮生长因子受体-2(HER-2)的乳腺癌细胞凋亡的作用机制和治疗效果。方法通过建立HER2过表达乳腺癌裸鼠皮下移植瘤模型,并将其分为对照组、曲妥珠单抗组、紫杉醇组和曲妥珠单抗联合紫杉醇组,分别给予相对应的药物治疗21 d。统计分析各组裸鼠的肿瘤体积、瘤重和抑瘤率,并使用Annexin V/PI双染色法检测细胞凋亡率。使用免疫组化检测Ki-67、微血管密度(MVD)及血管内皮生长因子(VEGF)。结果曲妥珠单抗联合紫杉醇组的肿瘤体积增长最慢,在21 d时的体积远远小于其它各组(P<0.05);曲妥珠单抗联合紫杉醇组的瘤重最小,抑瘤率远远高于其它组(P<0.05);D组裸鼠的细胞凋亡率均高于A、B、C组,且差异有统计学意义(P<0.05);D组裸鼠的Ki-67、MVD密度及VEGF水平均显著低于其他各组(P<0.05)。结论曲妥珠单抗联合紫杉醇诱导过表达HER-2的乳腺癌细胞凋亡效果显著,可以有效抑制HER2过表达乳腺癌裸鼠皮下移植瘤的生长及血管生成,值得临床推广应用。

TCH方案在Her-2阳性乳腺癌新辅助治疗的临床疗效观察

目的探讨TCH(多西他赛+卡铂+曲妥珠单抗)方案在Her-2阳性乳腺癌新辅助治疗中的临床疗效。方法对21例Her-2阳性乳腺癌(ⅡB期～ⅢC期)术前行TCH方案的新辅助治疗4～6个周期,评价临床疗效,并中位随访2年观察无病生存率及总生存率。结果 21例患者中CR 16例(76.19%),其中达到PCR 13例(61.90%),PR 3例(14.29%),SD 2例(9.52%)。总有效率(CR+PR)达:90.48%,2年的无病生存率为95.23%,总生存率为100%。结论应用TCH方案行新辅助治疗可有效提高Her-2阳性乳腺癌患者的临床缓解率,使一部分患者获得保乳手术的机会,提高手术成功率,并改善患者的生存率。

HER-2过表达型乳腺癌的分子生物学基础及治疗进展

乳腺癌是一类受激素受体调控且高度异质性的恶性肿瘤,不同类型乳腺癌无病生存期、复发转移率及预后均不相同。其中HER-2过表达型乳腺癌恶性程度高、生存率低,预后相对较差。但却是曲妥珠单抗进行分子靶向治疗的较好的适应症,可极大的改善该类患者的生存率。但由于药物耐药性、靶向效率低等,乳腺癌的最终复发不可避免。针对曲妥珠单抗耐药以后的后续治疗成为新的研究热点,本文介绍了HER-2过表达型乳腺癌发生的分子生物学基础及相应的信号传导过程,及以此为基础开发了一系列新药。