Abstract PD10-04: Prognostic potential of mesenchymal circulating tumor cell-associated white blood cell clusters in patients with HER2-negative metastatic breast cancer

Background:Circulating tumor cells (CTCs), potentially involved in the metastatic cascade, may have direct interactions with immune cells during cancer dissemination, and correlate with the inflammatory state in the target organ of metastatic extravasation. Although positive CTC status has been validated as a prognostic marker in breast cancer, the interaction between immune cells and CTCs during the progress of Epithelial-mesenchymal transition (EMT), and the clinical implications of CTC-associated white blood cell clusters (CTC-WBC clusters) for metastatic breast cancer are largely uncharacterized. We investigated the predictive value of different phenotypes of CTC-WBC clusters as a prognostic biomarker in a prospective study for metastatic breast cancer. Methods:The prospective study enrolled 134 patients with HER2-negative metastatic breast cancer who underwent docetaxel plus capecitabine as first-line chemotherapy and subsequently used capecitabine as maintenance therapy from Nov 2013 to Sep 2017. Serial peripheral blood samples were collected dynamically until disease progression for CTC detection using CanPatrol CTC enrichment technique. CTCs were isolated using a filter-based method combined with an RNA in situ hybridization method based on the branched DNA signal amplification technology according to EMT markers. Follow-up data collection was conducted until May 2019 and data analysis was performed in June 2019. Kaplan-Meier analysis and Cox proportional hazards regression analysis were performed to investigate the prognostic value of CTC-WBC clusters. Results:Median age of the 134 female patients was 51.0 years (range,21 to 73 years), and 119 (88.8%) of them were estrogen receptor-and/or progesterone receptor-positive. Median progression-free survival (PFS) was 9.9 months (95% CI, 8.1 to 11.6 months). 116 (86.6%) of the 134 patients had detectable CTCs at baseline with a mean number of 8 CTCs per 5 ml of blood, including epithelial CTCs, biphenotypic epithelial/mesenchymal CTCs and mesenchymal CTCs. Among them, CTC-WBC clusters were detectable in 9 patients, of whom 5 patients had mesenchymal CTCs contained in the CTC-WBC clusters. The patients with at least one detectable mesenchymal CTC-WBC clusters were characterized by significantly worse PFS, when compared with the patients with no mesenchymal CTC-WBC clusters (10.2 months vs 6.3 months, P=0.046), as well as the patients with at least one CTC per 5 ml blood (10.7 months vs 6.3 months, P=0.040). However, the presence of total CTC-WBC cluster regardless of CTC phenotypes was correlated with no significant survival difference in the cohort (10.0 months vs 8.6 months, P=0.913). Conclusions: Our data provide evidence that the emergence of mesenchymal CTC-WBC clusters before treatment is associated with significantly poorer PFS in HER2-negative metastatic breast cancer patients underwent first-line chemotherapy, which may be used as a parameter to predict the clinical outcomes for chemotherapy. This study validated the prognostic value of CTC-WBC cluster underwent mesenchymal transformation in a prospective cohort constituted by relatively homogeneous participants who were all HER2-negative metastatic breast cancer underwent docetaxel plus capecitabine as first-line chemotherapy. The results could provide evidence for mesenchymal CTC-WBC cluster to serve as a potential biomarker for individual therapy. However, limited sample size influenced the statistical power to draw firm conclusions. Thus, further large-scale external validation containing data of overall survival is warranted. Citation Format: Xiuwen Guan, Chunxiao Li, Xiaoying Sun, Lixi Li, Zongbi Yi, Binliang Liu, Jiasen Xu, Binghe Xu, Fei Ma. Prognostic potential of mesenchymal circulating tumor cell-associated white blood cell clusters in patients with HER2-negative metastatic breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr PD10-04.