地舒单抗对新辅助治疗乳腺癌患者播散肿瘤细胞（DTCs）的影响：GeparX 转化亚研究。
The effect of denosumab on disseminated tumor cells (DTCs) of breast cancer patients with neoadjuvant treatment: a GeparX translational substudy.
机构信息
Department of Gynecology and Obstetrics, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Fetscherstraße 74, 01307, Dresden, Germany.
National Center for Tumor Diseases (NCT), Dresden, Germany: German Cancer Research Center (DKFZ), Heidelberg, Germany; Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany; Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Dresden, Germany.
出版信息
Breast Cancer Res. 2023 Mar 28;25(1):32. doi: 10.1186/s13058-023-01619-2.
BACKGROUND
Disseminated tumor cells (DTCs) in the bone marrow are observed in about 40% at primary diagnosis of breast cancer and predict poor survival. While anti-resorptive therapy with bisphosphonates was shown to eradicate minimal residue disease in the bone marrow, the effect of denosumab on DTCs, particularly in the neoadjuvant setting, is largely unknown. The recent GeparX clinical trial reported that denosumab, applied as an add-on treatment to nab-paclitaxel based neoadjuvant chemotherapy (NACT), did not improve the patient's pathologic complete response (pCR) rate. Herein, we analyzed the predictive value of DTCs for the response to NACT and interrogated whether neoadjuvant denosumab treatment may eradicate DTCs in the bone marrow.
METHODS
A total of 167 patients from the GeparX trial were analyzed for DTCs at baseline by immunocytochemistry using the pan-cytokeratin antibody A45-B/B3. Initially DTC-positive patients were re-analyzed for DTCs after NACT ± denosumab.
RESULTS
At baseline, DTCs were observed in 43/167 patients (25.7%) in the total cohort, however their presence did not predict response to nab-paclitaxel based NACT (pCR rates: 37.1% in DTC-negative vs. 32.6% DTC-positive; p = 0.713). Regarding breast cancer subtypes, the presence of DTCs at baseline was numerically associated with response to NACT in TNBC patients (pCR rates: 40.0% in DTC-positive vs. 66.7% in DTC-negative patients; p = 0.16). Overall, denosumab treatment did not significantly increase the given DTC-eradication rate of NACT (NACT: 69.6% DTC-eradication vs. NACT + denosumab: 77.8% DTC-eradication; p = 0.726). In TNBC patients with pCR, a numerical but statistically non-significant increase of DTC-eradication after NACT + denosumab was observed (NACT: 75% DTC-eradication vs. NACT + denosumab: 100% DTC-eradication; p = 1.00).
CONCLUSION
This is the first study worldwide, demonstrating that neoadjuvant add-on denosumab over a short-term period of 24 months does not increase the DTC-eradication rate in breast cancer patients treated with NACT.
背景
在乳腺癌的初次诊断中，约有 40%的患者骨髓中存在弥散性肿瘤细胞（DTCs），且这些患者的生存预后较差。虽然双膦酸盐类抗吸收药物的应用可消除骨髓中的微小残留病灶，但地舒单抗对 DTCs 的影响，特别是在新辅助治疗环境中，仍知之甚少。最近的 GeparX 临床试验报告称，地舒单抗作为基于nab-紫杉醇的新辅助化疗（NACT）的附加治疗，并未提高患者的病理完全缓解（pCR）率。在此，我们分析了 DTCs 对 NACT 反应的预测价值，并探讨了新辅助地舒单抗治疗是否可以消除骨髓中的 DTCs。
方法
对 GeparX 试验中的 167 例患者进行了基线 DTCs 分析，采用泛细胞角蛋白抗体 A45-B/B3 进行免疫细胞化学检测。最初，对接受 NACT±地舒单抗治疗的 DTC 阳性患者进行了 DTCs 的重新分析。
结果
在总队列中，167 例患者中有 43 例（25.7%）在基线时存在 DTCs，但它们的存在并不能预测基于 nab-紫杉醇的 NACT 的反应（pCR 率：DTC 阴性组为 37.1%，DTC 阳性组为 32.6%；p=0.713）。关于乳腺癌亚型，基线时存在 DTCs 与三阴性乳腺癌（TNBC）患者对 NACT 的反应呈数值相关（pCR 率：DTC 阳性组为 40.0%，DTC 阴性组为 66.7%；p=0.16）。总体而言，地舒单抗治疗并未显著提高 NACT 既定的 DTC 消除率（NACT：69.6% DTC 消除率，NACT+地舒单抗：77.8% DTC 消除率；p=0.726）。在接受 NACT 治疗后获得 pCR 的 TNBC 患者中，尽管无统计学意义，但观察到 NACT+地舒单抗后 DTC 消除率的数值增加（NACT：75% DTC 消除率，NACT+地舒单抗：100% DTC 消除率；p=1.00）。
结论
这是全球首次研究表明，在 24 个月的短期治疗中，新辅助添加地舒单抗不会增加接受 NACT 治疗的乳腺癌患者的 DTC 消除率。
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