A Single-Arm Phase II Clinical Trial of Fulvestrant Combined with Neoadjuvant Chemotherapy of ER+/HER2– Locally Advanced Breast Cancer: Integrated Analysis of 18F-FES PET-CT and Metabolites with Treatment Response
- Author:
Qing SHAO
1
;
Ningning ZHANG
;
Xianjun PAN
;
Wenqi ZHOU
;
Yali WANG
;
Xiaoliang CHEN
;
Jing WU
;
Xiaohua ZENG
Author Information
- Publication Type:Original Article
- From:Cancer Research and Treatment 2025;57(1):126-139
- CountryRepublic of Korea
- Language:English
-
Abstract:
Purpose: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.
Materials and Methods: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.
Results: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.
Conclusion: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.
