Abstract B19: The impact of circulating tumor cells on treatment response in early breast cancer patients with hormone receptor-positive and HER2 positive who underwent the neoadjuvant therapy
Authors: Bae Soong June , Park Soeun , Cha Chi Hwan , Kim Dooreh , Lee Janghee , Ahn Sung Gwe , Jeong Joon 
Published: June 2020

Abstract
Introduction: Accumulating evidence has described that circulating tumor cells (CTCs) imply a poor prognosis in patients with early breast cancer. In this study, we evaluated the association between CTCs and response of neoadjuvant therapy in patients with hormone receptor (HR)-positive and HER2-positive breast cancer.
Method: The HERAKLES study was a prospective single-arm, multicenter, phase II trial designed to evaluate the efficacy and safety of letrozole and trastuzumab for neoadjuvant therapy in postmenopausal patients with HR-positive and HER2-positive breast cancer (NCT02214004). All patients received trastuzumab every 3 weeks for eight cycles and daily letrozole for 24 weeks, followed by the surgery. After neoadjuvant therapy, the clinical response was assessed by the radiologic modalities. The CTCs were investigated by using a microfabricated porous filter in which the size of the square pores was optimized as 8.5 × 8.5 μm for the nickel electroformed membrane filter from 10mL of whole blood. Then, immunofluorescence staining was conducted with antibodies against CD45, EpCAM, cytokeratins, and then counterstained with DAPI. The CTCs were determined as DAPI-positive, EpCAM-positive, CK-positive, and CD45-negative cells. The CTCs analysis before and after neoadjuvant therapy was performed in 21 patients. In addition, we classified the patients into 4 groups: Group A, CTC-negative at both times (n=4); Group B, presence of CTC at pretreatment and CTC-negative at post-treatment (n=4); Group C, CTC-negative at pretreatment and presence of CTC at post-treatment (n=6); Group D, presence of CTC at both times (n=7).
Results: The CTCs were detected in 11 (52.4%; median CTCs count, 2; range, 1-26) patients at pre-treatment and 13 (61.9%; median CTCs count, 4; range, 1-11) patients at post-treatment. CTC detection and CTC changes after neoadjuvant therapy were not associated with primary tumor characteristics. There was no patient with disease progression after neoadjuvant therapy in group A and B. However, the disease progression was observed in one (16.7%) patient in group C and two (28.6%) patients in group D (p=0.470). When the CTC was analyzed as continuous value, the CTCs were increased in all (the average change of CTCs, +6.0) patients with disease progression after neoadjuvant therapy, although the CTCs were increased in 7 (38.9%; the average change of CTCs, -1.3) of 18 patients without progression disease (p=0.09).
Conclusions: The increase in CTCs after neoadjuvant treatment, including aromatase inhibitor and trastuzumab, tended to be correlated with poor treatment response in HR+/HER2+ breast cancer patients, although it remains underpowered. Our results supported that the monitoring of CTCs may reflect the response to neoadjuvant aromatase inhibitor and trastuzumab therapy in HR+/HER2+ breast cancer.
Citation Format: Soong June Bae, Soeun Park, Chi Hwan Cha, Dooreh Kim, Janghee Lee, Sung Gwe Ahn, Joon Jeong. The impact of circulating tumor cells on treatment response in early breast cancer patients with hormone receptor-positive and HER2 positive who underwent the neoadjuvant therapy [abstract]. In: Proceedings of the AACR Special Conference on Advances in Liquid Biopsies; Jan 13-16, 2020; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(11_Suppl):Abstract nr B19.