Arnould L, Gelly M, Penault-Llorca F, Benoit L, Bonnetain F, Migeon C, Cabaret V, Fermeaux V, Bertheau P, Garnier J, Jeannin J-F, Coudert B
Department of Pathology, Centre G-F Leclerc, Dijon 21000, France.
Br J Cancer. 2006 Jan 30;94(2):259-67. doi: 10.1038/sj.bjc.6602930.
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.
本研究通过免疫组织化学（IHC）评估了HER2阳性原发性乳腺癌患者在接受曲妥珠单抗新辅助原发性全身治疗（PST）期间的免疫细胞反应。总共23例IHC 3+原发性乳腺癌患者接受了曲妥珠单抗联合多西他赛治疗。分别记录了9例（39%）患者的病理完全缓解和14例（61%）患者的部分缓解。病例匹配对照包括接受不含曲妥珠单抗的基于多西他赛的PST治疗的患者（D组；n = 23）或接受不含多西他赛或曲妥珠单抗的PST治疗的患者（非紫杉烷、非曲妥珠单抗，NT-NT组；n = 23）。所有手术标本由两名独立病理学家进行盲法分析，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估。对潜在的细胞溶解细胞进行颗粒酶B和TiA1染色。还对残留肿瘤细胞中的HER2表达进行了评估。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TiA1的淋巴细胞表达增加有关。本研究支持免疫（特别是NK细胞）反应在曲妥珠单抗治疗乳腺癌机制中的体内作用。这些结果表明，曲妥珠单抗加紫杉烷可导致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。
