Minghui Li,1,* Yuelin Liu,1,* Xu Han,1,* Tao Li,2 Zhizheng Zhang,1 Ningyi Xue,1 Mengdi Liang,1 Ge Ma,1 Tiansong Xia1 

1Department of Breast Surgery, The First Affiliated Hospital with Nanjing Medical University, Nanjing, 210029, People’s Republic of China; 2Department of Pathology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, 210029, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Tiansong Xia; Ge Ma, Department of Breast Surgery, The First Affiliated Hospital with Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, People’s Republic of China, Tel +86-25-83718836, Email xiatsswms@163.com; ntmage@sina.com

Background: Aneuploid circulating endothelial cells (CECs) are an indicator in breast cancer (BC). Significant changes of aneuploid CECs occurred during neoadjuvant chemotherapy (NCT). This study aimed to explore the predictive and prognostic values of aneuploid CECs in locally advanced breast cancer (LABC) patients with different NCT responses.
Methods: Breast cancer patients received an EC4-T4 NCT regimen. A novel subtraction enrichment and immunostaining fluorescence in situ hybridization (SE-iFISH) strategy was applied for the detection of CECs (CD45–/CD31+/DAPI+). Receiver operating characteristic (ROC) curves were plotted to evaluate the predictive value of aneuploid CEC counts in distinguishing NCT-resistant patients from sensitive ones. All patients were observed for progression-free survival (PFS) and overall survival (OS).
Results: The CEC counts at any time point did not show the ability to predict the efficacy of NCT. The difference in the CECs between post-chemotherapy levels and baseline could be sufficient to distinguish chemotherapy-resistant cases from other cases in Hormone+Her-2-/+ (HR+) BC patients. Patients with reduction of CECs after all courses of NCT were associated with higher probability of PFS.
Conclusion: Variations in aneuploid CECs during NCT may predict chemotherapy response in patients with HR+ breast cancer. The decrease in the number of aneuploid CECs after all courses of NCT indicates better treatment outcomes in patients with LABC.

Keywords: circulating endothelial cells, aneuploidy, neoadjuvant chemotherapy, prognosis, locally advanced breast cancer