Combined effects of neoadjuvant letrozole and zoledronic acid on γδT cells in postmenopausal women with early-stage breast cancer
Combined effects of neoadjuvant letrozole and zoledronic acid on γδT cells in postmenopausal women with early-stage breast cancer
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DOI：
10.1016/j.breast.2017.12.017
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发表时间：
2018-04-01
期刊：
影响因子：
3.9
通讯作者：
Toi, Masakazu
中科院分区：
文献类型：
--
作者：
Sugie, Tomoharu;Suzuki, Eiji;Toi, Masakazu
引言：辅助双膦酸盐可改善绝经后乳腺癌的预后。然而，临床结果和免疫调节之间的关联，他们仍然是uncleared.Methods：在这个前瞻性的，开放标签的第二阶段研究，绝经后妇女雌激素受体阳性和人表皮生长因子受体2阴性的早期乳腺癌接受新辅助来曲唑（LET）一个月，然后用单剂量的唑来膦酸治疗。患者在手术前接受了额外5个月的LET治疗。主要终点是通过MRI通过直径确定的肿瘤客观缓解率（ORR）。ORR和γ δ T细胞频率之间的关联被评估为次要终点。结果：在60例患者中，55例患者可通过MRI评估反应。唑来膦酸LET的ORR为38.2%（21/55），与历史对照（45%）相当。在整个治疗过程中观察到V δ 2 T细胞亚群的频率降低，并且V δ 2 T细胞被激活6个月。在计划的亚组分析中，与频率高的患者相比，唑来膦酸输注前V δ 2 T细胞频率低的患者发生了有利的肿瘤缓解（59.3% [16/27] vs 17.9% [5/28]，p = 0.002）。结论：这些结果表明，新辅助LET与唑来膦酸不能达到整体效果的局部肿瘤反应。然而，γ δ T细胞频率低的患者将受益于包括唑来膦酸的治疗。(UMIN 000008701）。(C)2018爱思唯尔有限公司版权所有
Introduction: Adjuvant bisphosphonates lead to better prognosis in postmenopausal breast cancer. However, the association between clinical outcomes and immune modulation by them is still unclear.Methods: In this prospective, open-label phase II study, postmenopausal women with estrogen receptor-positive and human epidermal growth factor receptor 2-negative early-stage breast cancer received neoadjuvant letrozole (LET) for one month, followed by treatment with a single dose of zoledronic acid. The patients underwent an additional 5 months of treatment with LET prior to surgery. The primary endpoint was the tumor objective response rate (ORR) determined by diameter via MRI. The association between the ORR and gamma delta T cell frequencies was assessed as a secondary endpoint.Results: Out of sixty patients, 55 patients were evaluable for response by MRI. The ORR for LET with zoledronic acid was 38.2% (21/55), which was comparable to that of historical controls (45%). A decrease in the frequency of the V delta 2 T cell subset was observed throughout treatment, and V delta 2 T cells were activated for 6 months. In planned subgroup analyses, patients with low frequencies of V delta 2 T cells prior to zoledronic acid infusion experienced a favorable tumor response compared to those with high frequencies (59.3% [16/27] vs 17.9% [5/28], p = .002). There were no serious adverse events with this treatment regimen.Conclusion: These results showed that neoadjuvant LET with zoledronic acid could not achieve overall effect for local tumor response. However, patients with a low frequency of gamma delta T cells would benefit from the treatment including zoledronic acid. (UMIN 000008701). (C) 2018 Elsevier Ltd. All rights reserved.