A Single-Arm Phase II Clinical Trial of Fulvestrant Combined with Neoadjuvant Chemotherapy of ER+/HER2- Locally Advanced Breast Cancer: Integrated Analysis of <sup>18</sup>F-FES PET-CT and Metabolites with Treatment Response

This Phase II trial was objected to evaluate the efficacy and safety of adding fulvestrant to NCT in patients with ER+/HER2-locally advanced breast cancer (LABC).Additionally, the study aimed to investigate the association of 18 F-FES PET-CT and metabolites with efficacy. Materials and MethodsFulvestrant and EC-T regimen were given to ER+/HER2-LABC patients before surgery.At baseline, patients received 18 F-FES PET-CT scan, and plasma samples were taken for LC-MS analysis.The primary endpoint was ORR.Secondary endpoints included tpCR and safety. ResultsAmong the 36 patients enrolled, the ORR was 86.1%, the tpCR rate was 8.3%.The incidence of grade ≥3 TEAEs 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 SUVmax, SUVmean, TL-ER of 18 F-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 MP 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. ConclusionThis 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.