Trastuzumab-based treatment of HER2-positive breast cancer: an antibody-dependent cellular cytotoxicity mechanism?
Trastuzumab-based treatment of HER2-positive breast cancer: an antibody-dependent cellular cytotoxicity mechanism?
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基于曲妥珠单抗的HER2阳性乳腺癌治疗：抗体依赖性细胞毒性机制？
DOI：
10.1038/sj.bjc.6602930
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发表时间：
2006-01-30
影响因子：
8.8
通讯作者：
Coudert, B
中科院分区：
文献类型：
--
作者：
Arnould, L;Gelly, M;Penault-Llorca, F;Benoit, L;Bonnetain, F;Migeon, C;Cabaret, V;Fermeaux, V;Bertheau, P;Garnier, J;Jeannin, JF;Coudert, B
本研究通过免疫组织化学（IHC）评价了HER 2阳性原发性乳腺癌患者在曲妥珠单抗新辅助初次全身治疗（PST）期间的免疫细胞应答。共有23例IHC 3+原发性乳腺癌患者接受曲妥珠单抗联合多西他赛治疗。病理完全和部分反应分别记录9（39%）和14（61%）例患者。病例匹配对照包括接受紫杉醇为基础的PST（不含曲妥珠单抗）（D; n=23）或PST（不含多西他赛或曲妥珠单抗）（非紫杉烷、非曲妥珠单抗、NT-NT; n=23）治疗的患者。由两名独立的病理学家对所有手术标本进行盲法分析，并对B和T淋巴细胞、巨噬细胞、树突状细胞和自然杀伤（NK）细胞进行免疫组织化学评价。对潜在的细胞溶解细胞进行颗粒酶B和TiA 1染色。还在残留肿瘤细胞中评价了HER 2表达。与对照组相比，曲妥珠单抗治疗与肿瘤相关NK细胞数量显著增加以及颗粒酶B和TiA 1淋巴细胞表达增加相关。本研究支持在乳腺癌中曲妥珠单抗作用机制中免疫（特别是NK细胞）应答的体内作用。这些结果表明，曲妥珠单抗加紫杉烷类导致NK细胞活性增强，这可能部分解释了曲妥珠单抗和多西他赛在乳腺癌中的协同活性。
This study evaluated by immunohistochemistry (IHC) immune cell response during neoadjuvant primary systemic therapy (PST) with trastuzumab in patients with HER2-positive primary breast cancer. In all, 23 patients with IHC 3+ primary breast cancer were treated with trastuzumab plus docetaxel. Pathological complete and partial responses were documented for nine (39%) and 14 (61%) patients, respectively. Case-matched controls comprised patients treated with docetaxel-based PST without trastuzumab (D; n=23) or PST without docetaxel or trastuzumab (non-taxane, non-trastuzumab, NT–NT; n=23). All surgical specimens were blind-analysed by two independent pathologists, with immunohistochemical evaluation of B and T lymphocytes, macrophages, dendritic cells and natural killer (NK) cells. Potential cytolytic cells were stained for Granzyme B and TiA1. HER2 expression was also evaluated in residual tumour cells. Trastuzumab treatment was associated with significantly increased numbers of tumour-associated NK cells and increased lymphocyte expression of Granzyme B and TiA1 compared with controls. This study supports an in vivo role for immune (particularly NK cell) responses in the mechanism of trastuzumab action in breast cancer. These results suggest that trastuzumab plus taxanes lead to enhanced NK cell activity, which may partially account for the synergistic activity of trastuzumab and docetaxel in breast cancer.
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影响因子：
45.3
作者：
Cobleigh, MA;Vogel, CL;Slamon, DJ
通讯作者：
Slamon, DJ
影响因子：
11.2
作者：
Jackson, JG;Clair, PS;Brattain, MG
通讯作者：
Brattain, MG
影响因子：
56.9
作者：
KING, CR;KRAUS, MH;AARONSON, SA
通讯作者：
AARONSON, SA
DOI：
10.1002/ssu.10021
发表时间：
2003-01-01
期刊：
Seminars in surgical oncology
影响因子：
--
作者：
Singletary, S Eva;Greene, Frederick L
通讯作者：
Greene, Frederick L
影响因子：
45.3
作者：
Buzdar, AU;Ibrahim, NK;Hortobagyi, GN
通讯作者：
Hortobagyi, GN