Abstract P2-02-05: Dynamic circulating tumor cell changes in enumeration and HER2 expression during systemic therapy for metastatic breast cancer
Authors: Zhang Qiang , Qin Weijun , D'Amico Paolo , Davis Andrew A. , Jiao Jianhua , Gerratana Lorenzo , Jacob Saya L. , Zhang Youbin , Donahue Jeannine , Qiang Wenan , Shah Ami N , Behdad Amir , Flaum Lisa , Gradishar William , Platanias Leonidas C , Cristofanilli Massimo 
Published: March 2022

Abstract
Introduction: CTCs are tumor cells that circulate in the blood of patient with primary and MBC and, are responsible for seeing of metastasis. The monitoring of CTCs in MBC emerged as strong prognostic and possible predictive biomarker in oncology over the past couple of decades. Meanwhile, overexpression of HER2 protein has been associated with rapid cell division and worse prognosis of MBC. Here we report a significant correlation between dynamic CTCs enumeration and CTCs-HER2 expression during the systemic therapies, with potential implication to understand treatment resistance. Methods: A total of 298 whole blood samples (7.5ml/each) were collected from 149 patients with stage IV breast cancer (2016-2020) at the Northwestern University Robert H Lurie Comprehensive Cancer Center, before (Baseline) and 3 months after (Time point 2) initiation of systemic treatment. CTC enumerations were performed using the FDA approved CellSearch™ system (Menarini) which is specific for the intracellular protein cytokeratin (CK) in epithelial cells, DAPI stains the cell nucleus, anti-CD45-APC is specific for leukocytes, and anti-HER-2/neu-FLU is specific for HER-2/neu antigen. The CTCs were classified as CK+, EpCAM+, DAPI+ and CD45-. We developed a criteria for evaluation of HER2 expression by 4 different categories (0,1+,2+,3+) based on expression intensity in our lab (present in 2021 ASCO). In this study we included CTCs with all intensities of HER2 expression (1+ to 3+) which was standardized in our lab. Mann-Whitney U test was used for statistics. Results: Of the 149 baseline samples, CTC≥1 were found in 101 patients (67.8%). A change in CTCs between baseline and time point 2 for these 101 patients: Three groups were identified: Group 1: 33patients (33%) with increase CTCs; Group 2: 64 patients (63%) with decreased CTC; Group 3: 4 patients (4%) with no change The median increase of total CTCs and HER2+ CTCs in Group 1 were 7.0 and 2.0, respectively; the median decrease of total CTCs and HER2+ CTCs in Group 2 were 9.5 and 2.0, respectively. The change of HER2+ CTCs was significantly correlated with the change of total CTCs after systemic therapy, with the correlation coefficient as rs=0.662 (p&lt;0.001) for these 101 patients. A significant positive correlation between HER2+ CTCs and total CTCs were found in both Group 1 and Group 2, rs=0.717 (p&lt;0.001) and rs=0.604 (p&lt;0.001) respectively. Furthermore, the ratio of HER2+ CTCs (HER2+ CTCs/total CTCs) in both Group 1 and Group 2 was also significantly correlated with total CTCs after therapy with the corresponding correlation coefficient as rs=0.536 (p&lt;0.001) and rs=0.388 (p&lt;0.001) in Group 1 and Group 2, respectively. Conclusion: Our study demonstrated that dynamic changes of CTCs after systemic therapies, are positively correlated with the HER2 expression in CTCs in different levels of baseline CTCs amounts. Observation of HER2 expression and ratio in CTCs during the course of systemic therapy is useful in monitoring therapy efficacy and potential disease progress.
Citation Format: Qiang Zhang, Weijun Qin, Paolo D'Amico, Andrew A. Davis, Jianhua Jiao, Lorenzo Gerratana, Saya L. Jacob, Youbin Zhang, Jeannine Donahue, Wenan Qiang, Ami N Shah, Amir Behdad, Lisa Flaum, William Gradishar, Leonidas C Platanias, Massimo Cristofanilli. Dynamic circulating tumor cell changes in enumeration and HER2 expression during systemic therapy for metastatic breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-02-05.