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-158 多态性与基质肿瘤浸润淋巴细胞及接受曲妥珠单抗治疗的转移性HER2阳性乳腺癌患者的生存情况

-158 Polymorphism and Stromal Tumor-Infiltrating Lymphocytes and Survival among Patients with Metastatic HER2-Positive Breast Cancer Receiving Trastuzumab-Based Treatment.

作者信息

Chae Heejung, Yoo Changhoon, Yoon Jung-A, Lee Hee Jin, Kim Kyu-Pyo, Kim Jeong-Eun, Ahn Jin-Hee, Jung Kyung Hae, Gong Gyungyub, Kim Sung-Bae

机构信息

Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

出版信息

J Breast Cancer. 2018 Mar;21(1):45-50. doi: 10.4048/jbc.2018.21.1.45. Epub 2018 Mar 23.

DOI:10.4048/jbc.2018.21.1.45
PMID:29628983
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5880965/
Abstract

PURPOSE

The prognosis of human epidermal growth factor receptor 2 (HER2)-positive breast cancer has markedly improved since the introduction of trastuzumab. We aimed to evaluate the association between stromal tumor-infiltrating lymphocyte (sTIL) or polymorphisms and survival among patients with metastatic HER2-positive breast cancer who were treated with trastuzumab.

METHODS

A total of 56 women with recurrent or metastatic HER2-positive breast cancer who received the trastuzumab-taxane combination as first-line treatment were included in this retrospective analysis. The single-step multiplex allele-specific real-time polymerase chain reaction technique was employed for genotyping. sTILs were identified via immunohistochemical analysis of surgical (n=34, 60.7%) or biopsy specimens of metastatic lesions (n=22, 39.3%).

RESULTS

We classified patients based on the sTIL level (≤10% [n=44] or >10% [n=12]); high sTIL counts were more commonly observed in patients with hormone receptor-negative tumors than in those with hormone receptor-positive tumors (34.8% vs. 12.1%, =0.02). There was a significant association between high sTIL levels and longer progression-free survival in comparison to low sTIL levels (median, 28.4 months vs. 16.8 months; =0.03). With regard to the -158 genotype, patients were classified into the Phenylalanine/Phenylalanine group (23 patients, 41.1%), Phenylalanine/Valine group (23 patients, 41,1%), or Valine/Valine group (10 patients, 17.9%); these classifications were not associated with clinical outcomes.

CONCLUSION

High sTIL expression may be associated with better efficacy of trastuzumab-containing therapy in patients with metastatic HER2-positive breast cancer. However, this finding warrants further evaluation in the larger population.

摘要

目的

自曲妥珠单抗应用以来,人表皮生长因子受体2(HER2)阳性乳腺癌的预后有了显著改善。我们旨在评估基质肿瘤浸润淋巴细胞(sTIL)或基因多态性与接受曲妥珠单抗治疗的转移性HER2阳性乳腺癌患者生存率之间的关联。

方法

本回顾性分析纳入了56例接受曲妥珠单抗-紫杉烷联合方案作为一线治疗的复发或转移性HER2阳性乳腺癌女性患者。采用单步多重等位基因特异性实时聚合酶链反应技术进行基因分型。通过对手术标本(n = 34,60.7%)或转移病灶活检标本(n = 22,39.3%)进行免疫组织化学分析来鉴定sTIL。

结果

我们根据sTIL水平(≤10% [n = 44] 或>10% [n = 12])对患者进行分类;激素受体阴性肿瘤患者中高sTIL计数的观察频率高于激素受体阳性肿瘤患者(34.8% 对12.1%,P = 0.02)。与低sTIL水平相比,高sTIL水平与更长的无进展生存期之间存在显著关联(中位数,28.4个月对16.8个月;P = 0.03)。关于-158基因型,患者被分为苯丙氨酸/苯丙氨酸组(23例患者,41.1%)、苯丙氨酸/缬氨酸组(23例患者,41.1%)或缬氨酸/缬氨酸组(10例患者,17.9%);这些分类与临床结局无关。

结论

高sTIL表达可能与转移性HER2阳性乳腺癌患者含曲妥珠单抗治疗的更好疗效相关。然而,这一发现有待在更大规模人群中进一步评估。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d05/5880965/401372fd01f0/jbc-21-45-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d05/5880965/fe7cd0de4ca1/jbc-21-45-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d05/5880965/401372fd01f0/jbc-21-45-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d05/5880965/fe7cd0de4ca1/jbc-21-45-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d05/5880965/401372fd01f0/jbc-21-45-g002.jpg

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本文引用的文献

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Lancet Oncol. 2017 Jan;18(1):52-62. doi: 10.1016/S1470-2045(16)30631-3. Epub 2016 Dec 7.
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Tumor-Infiltrating Lymphocytes: A Predictive and Prognostic Biomarker in Neoadjuvant-Treated HER2-Positive Breast Cancer.肿瘤浸润淋巴细胞:新辅助治疗 HER2 阳性乳腺癌的预测和预后生物标志物。
Clin Cancer Res. 2016 Dec 1;22(23):5747-5754. doi: 10.1158/1078-0432.CCR-15-2338. Epub 2016 May 17.
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Analysis of in vitro ADCC and clinical response to trastuzumab: possible relevance of FcγRIIIA/FcγRIIA gene polymorphisms and HER-2 expression levels on breast cancer cell lines.曲妥珠单抗的体外抗体依赖性细胞介导的细胞毒性(ADCC)及临床反应分析:FcγRIIIA/FcγRIIA基因多态性与HER-2表达水平对乳腺癌细胞系的潜在相关性
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