Abstract P6-10-23: Presence of circulating tumor cell clusters and elevated platelet counts interactively predict disease progression in advanced-stage breast cancer patients
Authors: Wang Chun , Ye Zhong , Zhang Zhenchao , Abu-Khalaf Maysa , Silver Daniel , Lopez AnaMaria , Fellin Frederick , Bhattacharya Saveri , Jaslow Rebecca , Yao Kaelan , Toorkey Darayus , Pancholy Neha , Myers Ronald , Yang Hushan 
Published: March 2020

Abstract
Background: Circulating tumor cells (CTCs) and their clusters (CTC-clusters) are promising prognostic markers in breast cancer. Recently studies showed that platelets interact with tumor cells in the circulation and promote metastasis. However, no study has been reported to explore the effects of interactions between CTCs/CTC-clusters and platelets on the prognosis of breast cancer at the population level.
Methods: A total of 146 female advanced-stage breast cancer patients were included in this study. CTCs and CTC-clusters were enumerated using the CellSearch system. Platelet count was obtained from laboratory tests. The individual and joint effects of CTCs/CTC-clusters and platelets on progression free survival (PFS) were evaluated using the Cox proportional hazards model.
Results: Elevated CTCs (≥ 5 CTCs/7.5 mL), presence of CTC-clusters, or high platelet counts (≥ 400 × 109/L) were individually associated with PFS (hazard ratio [HR] 2.69, 2.71, and 1.79, respectively). We further stratified patients into three risk groups according to the status of CTCs/CTC-clusters in combination with the level of platelet counts, including: 1) low-risk group: for CTC-related analyses, low CTCs (&lt; 5 CTCs/7.5 mL) and platelet counts (&lt; 400 × 109/L); for CTC-cluster-related analyses, absence of CTC-cluster and low platelet counts; 2) medium-risk group: for CTC-related analyses, either elevated CTCs (≥ 5 CTCs/7.5 mL) or high platelet counts (≥ 400 × 109/L), but not both; for CTC-cluster-related analyses, either presence of CTC-clusters or high platelet counts, but not both; 3) high-risk group: for CTC-related analyses, both elevated CTCs and high platelet counts; for CTC-cluster-related analyses, presence of CTC-clusters and high platelet counts. A significantly increased risk for disease progression was observed in high-risk patients, especially in patients with both CTC-clusters and high platelet counts (adjusted HR 16.06, P = 0.0003, log-rank P&lt; 0.0001). Furthermore, we identified a multiplicative interaction between CTC-clusters and platelets on PFS (P for interaction = 0.0483), and the patients with both CTC-clusters and high platelet counts had the shortest time of development of new metastatic sites.
Conclusions: Our results indicated the effects of interactions between the presence of CTC-clusters and high platelet counts on tumor progression and dissemination in breast cancer. Future studies are warranted to validate our findings and explore their biological mechanisms and clinical relevance.
Citation Format: Chun Wang, Zhong Ye, Zhenchao Zhang, Maysa Abu-Khalaf, Daniel Silver, AnaMaria Lopez, Frederick Fellin, Saveri Bhattacharya, Rebecca Jaslow, Kaelan Yao, Darayus Toorkey, Neha Pancholy, Ronald Myers, Hushan Yang. Presence of circulating tumor cell clusters and elevated platelet counts interactively predict disease progression in advanced-stage breast cancer patients [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 P6-10-23.