Abstract PS2-20: Prognostic value of baseline circulating tumor cells (CTCs) enumerations is for stage III and stage IV breast cancer
Authors: Qiang Zhang, Zheng Cai, Lorenzo Gerratana, Paolo D'Amico, Andrew A. Davis, Saya Liz Jacob, Elena Vagia, Ami N Shah, Lisa Flaum, Youbin Zhang, Wenan Qiang, Firas Wehbe, Amir Behdad, William Gradishar, Leonidas C Platanias, Massimo Cristofanilli
Journal: Cancer Research (2021)

Abstract Introduction: Prognosis of metastatic breast cancer (MBC) is initially predicted by the cancer’s characteristics based on AJCC TNM system, including the size of the cancer tumor, invasion into nearby tissue, lymph nodes and other parts of the body beyond the breast. Although additional information including hormone-receptor status, HER2 status, and possibly Oncotype DX score contributed to improve prognostic evaluation, predicting clinical outcomes and treatment benefit for MBC is still a challenge in clinic because of the clinical and biologically heterogeneous condition. We recently reported that CTCs enumeration can classify MBC in two distinct prognostic groups independently of clinical and molecular characteristics (Crit Rev Oncol Hematol. 2019). Moreover, our group reported that CTCs is associated with HER2 expression in MBC which may indicate more aggressive tumor (2019 AACR #1919). Here we compared CTCs enumeration of Stage III and Stage IV, which would be helpful to evaluate the MBC metastasis capability and treatment in clinic. Methods: The study included 38 specimens prospectively collected under IRB-approved protocol from 38 patients with Stage III MBC, and 254 specimens from 254 patients with stage IV MBC who received standard systemic treatments based on disease subtypes at NMH (2016-2020). Duplicate whole blood samples (7.5ml/each) were collected in EDTA tubes from these patients who were longitudinally characterized for CTCs before therapy (baseline). CTCs enrichment and enumeration were performed in FDA approved semi-automated fluorescence CELLTRACKS ANALYZERII® System (Menarini) by using CELLSEARCH® CXC Kit contains antibodies targeting the Epithelial Cell Adhesion Molecule (EpCAM) antigen for capturing CTCs, anti-CK-PE which is specific for the intracellular protein cytokeratin in epithelial cells, DAPI for staining the cell nucleus, anti-CD45-APC is specific for leukocytes (2019 ASCO #1036). The CTCs were classified based on morphology and correct phenotype as CK+, DAPI+ and CD45-. Kruskal-Wallis test was used for statistics. Results: Patients were classified as Luminal, HER2 positive and TNBC disease subtypes in 46.6%, 46.7% and 6.7% respectively in Stage III patients, and 54%, 18% and 28% respectively in Stage IV patients. The patients at age above 50 were 26.% in Stage III group and 68% in Stage IV group respectively. IBC patients represented 61.5% and 33.5% of Stage III and Stage IV patients respectively. Metastasis in liver, lung and bone were diagnosed in 40.7%, 40.2% and 62.8% in Stage IV patients. CTC negative (&amp;lt;5 CTCs) and positive (≥5CTCs) patients were identified in 32/38 (84.22%, group 1) and 6/38 (15.78%, group 2) respectively in Stage III patients, and 149/254 (59%, Stage IV indolent ) and 105/254 (41%, Stage IV aggressive ) respectively in Stage IV patients. Patients in Group 1 have a significantly less recurrence probability than patients in Group 2 (p=0.015). Correspondingly, patients with Stage IV indolent also had significantly longer survival than patients with Stage aggressive disease (p=0.0021). When comparing the all population, Group 1 patients still have the highest survival probability (p=0.00057) within 47 months follow-up survey. More interesting, there was no any CTC-clusters found in all Stage III patients when there were 28 out of 254 stage IV patients (11.02%) were detected with CTC-clusters, who had the worst prognosis in compared to either Stage IV patients without CTC-clusters or Stage III patients (p=0.00035). Conclusions: In this study, we showed that enumeration of baseline CTC and CTC-clusters correlated with worse prognosis even the patients were pathologically diagnosed for the same stage, which provided an additional measure to predict disease recurrence after systemic therapies especially for Stage III MBC patients. Citation Format: Qiang Zhang, Zheng Cai, Lorenzo Gerratana, Paolo D'Amico, Andrew A. Davis, Saya Liz Jacob, Elena Vagia, Ami N Shah, Lisa Flaum, Youbin Zhang, Wenan Qiang, Firas Wehbe, Amir Behdad, William Gradishar, Leonidas C Platanias, Massimo Cristofanilli. Prognostic value of baseline circulating tumor cells (CTCs) enumerations is for stage III and stage IV breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS2-20.