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71.
Ahn HK Lee S Park YH Sohn JH Jo JC Ahn JH Jung KH Park S Cho EY Lee JI Park W Choi DH Huh SJ Ahn JS Kim SB Im YH 《Neuro-oncology》2012,14(8):1105-1113
The purpose of this study is to validate the recently published Breast-Graded Prognostic Assessment (GPA) and propose a new prognostic model and nomogram for patients with brain parenchymal metastases (BM) from breast cancer (BC). We retrospectively investigated 171 consecutive patients who received a diagnosis of BM from BC during 2000-2008. We appraised the recently proposed Sperduto's BC-specific GPA in training cohort through Kaplan-Meier survival curve using log-rank test and area under the curve for the BC-GPA predicting overall survival at 1 year and developed a new nomogram to predict outcomes using multivariate Cox-regression analysis. By putting the Sperduto's Breast-GPA together with our nomogram, we developed a new prognostic model. We validated our new prognostic model with an independent external patient cohort from 2 institutes for the same period. On the basis of our Cox-regression analysis, therapeutic effect of trastuzumab and status of extracranial systemic disease control were incorporated into our new prognostic model in addition to Karnofsky performance status, age, and hormonal status. Our new prognostic model showed significant discrimination in median survival time, with 3.7 months for class I (n = 15), 7.8 months for class II (n = 82), 10.7 months for class III (n = 42), and 19.2 months for class IV (n = 32; P < .0001). The new prognostic model accurately predicted survival among patients with BC from BM in an external validation cohort (P < .0001). We propose a new prognostic model and a nomogram reflecting the different biological features of BC, including treatment effect and status of extracranial disease control, which was excellently validated in an independent external cohort. 相似文献
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Allan Lipton MD Wolfgang J. Köstler MD Kim Leitzel MSc Suhail M. Ali MD Jeff Sperinde PhD Jodi Weidler PharmD Agnes Paquet MSc Thomas Sherwood MD Weidong Huang MD PhD Michael Bates MD the Trastuzumab Response Biomarker Group 《Cancer》2010,116(22):5168-5178
BACKGROUND:
Only a portion of breast cancer patients currently selected for trastuzumab therapy respond.METHODS:
Using a novel assay (HERmark) to quantify total human epidermal growth factor receptor 2 (HER2) expression, the authors examined outcomes in 102 trastuzumab‐treated metastatic breast cancer patients previously assessed as immunohistochemistry (IHC) 3+ by local but not central IHC, or fluorescence in situ hybridization (FISH) positive, and then retested by central FISH.RESULTS:
Of 102 MBC patients previously scored as IHC 3+ or 2+/FISH‐positive and treated with trastuzumab‐containing regimens, 98 had both central FISH and HER2 total expression values. Sixty‐six of 76 central FISH‐positive patients (87%) had high HER2 total expression levels (concordant positive), and 19 of 22 central FISH‐negative patients (86%) were HER2 total expression low (concordant negative). Fourteen percent (3 of 22) of central FISH‐negative patients were HER2 total expression high (discordant HER2 total expression high), and 13% (10 of 76) of central FISH‐positive patients were HER2 total expression low (discordant HER2 total expression low). The concordant positive group had a significantly longer time to progression (TTP, median = 11.3 months) compared with the concordant negative group (median TTP, 4.5 months; hazard ratio [HR] = 0.42, P < .001), and also compared with the discordant HER2 total expression low group (median TTP, 3.7 months; HR = 0.43, P = .01). The discordant HER2 total expression low group behaved similarly compared with concordant negatives (HR = 1, P = .99). In analyses restricted to central FISH‐positive patients only (n = 77), Cox proportional hazards multivariate regression identified HER2 total expression as an independent predictor of TTP (HR = 0.29, P = .0015) and overall survival (HR = 0.19, P < .001).CONCLUSIONS:
A subset of patients with HER2 gene amplification by FISH express low levels of HER2 protein and have reduced response to trastuzumab‐containing therapy, similar to FISH‐negative patients. This cohort represents a training dataset, and the observed relationships and derived cutoffs require validation in an independent cohort of trastuzumab‐treated metastatic breast cancer patients. Cancer 2010. © 2010 American Cancer Society. 相似文献75.
Trastuzumab in Human Epidermal Growth Factor Receptor 2‐Positive Early Breast Cancer: Results of a Prospective,Noninterventional Study on Routine Treatment Between 2006 and 2012 in Germany 下载免费PDF全文
76.
目的:探索Erbin表达缺失导致Her2阳性的人乳腺癌细胞MDA-453对曲妥珠单抗敏感性的影响。方法设计、构建含人Erbin基因特异性的短发夹RNA( shRNA)及对照shRNA的干扰载体,转染MDA-453人乳腺癌细胞。经G418加压筛选,获得稳定敲低Erbin的MDA-453细胞( MDA-453-Erbin sh)和稳定表达对照shRNA的MDA-453细胞( MDA-453-NC),以后者作为对照细胞。应用Western印迹法检测MDA-453-NC和MDA-453-Erbin sh细胞中Erbin表达水平。分别通过细胞增殖活性实验及细胞集落形成实验,观察敲低Erbin的MDA-453细胞对曲妥珠单抗敏感性的变化。通过免疫组化染色法,分析Erbin在人乳腺癌及正常乳腺组织中的表达。结果建立了稳定敲低Erbin的MDA-453细胞株,发现敲低Erbin表达可诱导MDA-453细胞对曲妥珠单抗产生抗性。与正常乳腺上皮组织相比,人乳腺癌组织标本中Erbin表达水平降低。结论 Erbin表达缺失可能影响乳腺癌对曲妥珠单抗治疗的敏感性。 相似文献
77.
《Journal of chemotherapy (Florence, Italy)》2013,25(5):632-639
AbstractA vascular endothelial growth factor (VEGF) inhibitor might enhance metronomic chemotherapy in previously treated metastatic breast cancer (MBC) patients. Anthra-cycline and taxane refractory MBC patients were given cyclophosphamide 50 mg p.o. daily, methotrexate 1 mg/kg i.v. every 14 days, and bevacizumab 10 mg/kg i.v. every 14 days. Trastuzumab was added in HER2-overexpressing tumors. 24 patients were enrolled and 22 were evaluable. All tumors had histologic grade II-III and most patients had ≥2 metastatic sites. After a median follow-up of 7.7 months the response rates were: complete response (CR) 0%, partial response (PR) 31.8% (95% CI 13.9-54.9%), stable disease for ≥24 weeks (SD) 31.8% (95% CI 13.9-54.9%). Clinical benefit (CB= CR + PR + SD>24w) 63.6% (95% CI 40.7-82.8%). Median progression-free survival (PFS) was 7.5 months; overall survival (OS) was 13.6 months. HER2-overex-pressing or high proliferative-index tumors had better 6-month PFS (75% vs. 34% in HER-negative tumors P= 0.043; 67% vs. 0% in Ki-67 ≥20% tumors, P = 0.015). Adverse effects were mild. The combination of bevacizumab and a metronomic-based chemotherapy was effective, well tolerated and provided clinical benefit in heavily-treated MBC patients. 相似文献
78.
《Expert review of anticancer therapy》2013,13(12):1883-1890
Trastuzumab, a humanized monoclonal antibody directed against HER2, used alone or in combination with chemotherapy, has shown significant clinical benefit in improving survival in the metastatic setting, as well as halving the recurrence rate and improving survival in HER2-positive early breast cancer. Lapatinib is an orally active, reversible, small-molecule tyrosine kinase inhibitor that potently inhibits both HER1 and HER2 tyrosine kinase activity. This agent is the most advanced in terms of clinical trials and has been shown to have a favorable safety profile. Owing to the promising activity seen in advanced breast cancer, lapatinib is the ideal candidate for testing in the adjuvant setting. Adjuvant Lapatinib and/or Trastuzumab Treatment Optimisation (ALTTO) is a four-arm randomized trial designed to compare trastuzumab and lapatinib in women with early-stage HER2-positive breast cancer. Specifically, ALTTO will examine which anti-HER2 agent is more effective and which is their best schedule of administration, namely, what benefit will be derived by taking the drugs separately, in tandem order or in combination. Overall, 8000 patients will be enrolled worldwide. 相似文献
79.
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M M Wattenberg A R Kwilas S R Gameiro A P Dicker J W Hodge 《British journal of cancer》2014,110(6):1472-1480