Shao Qing, Zhang Ningning, Pan Xianjun, Zhou Wenqi, Wang Yali, Chen Xiaoliang, Wu Jing, Zeng Xiaohua
Department of Breast Cancer Center, Chongqing University Cancer Hospital, Chongqing, China.
Department of Nuclear Medicine, Chongqing University Cancer Hospital, Chongqing, China.
Cancer Res Treat. 2025 Jan;57(1):126-139. doi: 10.4143/crt.2023.1251. Epub 2024 Jul 9.
This Phase II trial was objected to evaluate the efficacy and safety of adding fulvestrant to neoadjuvant chemotherapy in patients with estrogen receptor (ER)+/human epidermal growth factor receptor 2 (HER2)- locally advanced breast cancer (LABC). Additionally, the study aimed to investigate the association of 16α-18F-fluoro-17β-fluoroestradiol (18F-FES) positron emission tomography (PET)-computed tomography (CT) and metabolites with efficacy.
Fulvestrant and EC-T regimen were given to ER+/HER2- LABC patients before surgery. At baseline, patients received 18F-FES PET-CT scan, and plasma samples were taken for liquid chromatography-mass spectrometry analysis. The primary endpoint was objective response rate (ORR). Secondary endpoints included total pathologic complete response (tpCR) and safety.
Among the 36 patients enrolled, the ORR was 86.1%, the tpCR rate was 8.3%. The incidence of grade ≥ 3 treatment-emergent adverse events was 22%. The decrease in ER value in sensitive patients was larger than that in non-sensitive patients, as was Ki-67 (p < 0.05). The maximum standardized uptake value, mean standardized uptake values, total lesion ER expression of 18F-FES PET-CT in sensitive patients were significantly higher than those in non-sensitive patients (p < 0.05). Moreover, these parameters were significantly correlated with Miller and Payne grade and the change in ER expression before and after treatment (p < 0.05). Thirteen differential expressed metabolites were identified, which were markedly enriched in 19 metabolic pathways.
This regimen demonstrated acceptable toxicity and encouraging antitumor efficacy. 18F-FES PET-CT might serve as a tool to predict the effectiveness of this therapy. Altered metabolites or metabolic pathways might be associated with treatment response.
本II期试验旨在评估在雌激素受体（ER）阳性/人表皮生长因子受体2（HER2）阴性的局部晚期乳腺癌（LABC）患者中，在新辅助化疗基础上加用氟维司群的疗效和安全性。此外，该研究旨在探讨16α-18F-氟-17β-雌二醇（18F-FES）正电子发射断层扫描（PET）-计算机断层扫描（CT）及代谢产物与疗效的相关性。
对ER阳性/HER2阴性的LABC患者在手术前给予氟维司群和EC-T方案。在基线时，患者接受18F-FES PET-CT扫描，并采集血浆样本进行液相色谱-质谱分析。主要终点为客观缓解率（ORR）。次要终点包括总病理完全缓解（tpCR）和安全性。
在入组的36例患者中，ORR为86.1%，tpCR率为8.3%。≥3级治疗中出现的不良事件发生率为22%。敏感患者的ER值下降幅度大于非敏感患者，Ki-67也是如此（p<0.05）。敏感患者18F-FES PET-CT的最大标准化摄取值、平均标准化摄取值、总病灶ER表达均显著高于非敏感患者（p<0.05）。此外，这些参数与米勒和佩恩分级以及治疗前后ER表达的变化显著相关（p<0.05）。鉴定出13种差异表达的代谢产物，它们在19条代谢途径中显著富集。
该方案显示出可接受的毒性和令人鼓舞的抗肿瘤疗效。18F-FES PET-CT可能作为预测该治疗有效性的工具。代谢产物或代谢途径的改变可能与治疗反应相关。
