Abstract PS2-14: Her2 expression in matched metastatic tumor and circulating tumor cells (ctcs) in breast cancer: Implications for profiling and monitoring of her2 status to help guide anti-her2 therapy
Authors: Stearns Vered , Lehman Jennifer , Mitchell Christine , Blouw Barbara , Huynh Lan , Singh Veena 
Published: February 2021

Abstract
INTRODUCTION: Despite improvements in early detection, 1 in 8 women in the US (12%) will develop invasive breast cancer over the course of her lifetime. Approximately 20% of breast cancer is HER2 positive. During treatment and at disease progression, HER2 receptor conversion may occur. Once metastatic, it may be difficult to access multiple metastatic sites or perform serial biopsies. Therefore, accuracy of results may be sub-optimal as tissue biopsy is a single time point collection and limited by sampling (inter-tumoral and intra-tumoral heterogeneity). A liquid biopsy is a contemporaneous non-invasive and cost-effective method that allows for collection and analysis of tumor material and includes circulating tumor cells (CTCs) or circulating tumor DNA (ctDNA). We compared prospectively the expression of HER2 in metastatic tumors to HER2 amplification in CTCs. METHODS: We enrolled patients with metastatic breast cancer in the Individualized Molecular Analyses Guide Efforts in Breast Cancer (IMAGE) II Study (NCT02965755). All patients regardless of subtype, had at least one line of therapy (chemotherapy, hormone therapy, or anti-HER2 therapy as appropriate). We analyzed HER2 status on tumor biopsies obtained 0-43 months (mean 7.3 months) prior to enrolling in IMAGE, and CTCs isolated from peripheral blood (PB) drawn ideally before starting a new treatment, 1-2 weeks after starting a new treatment and at the time of first restaging. CTCs were captured by Target Selector TM (Biocept) and analyzed for HER2 amplification by FISH. The biomarker expression profile on the metastatic tumor and CTCs were compared for each patient. Concordance of HER2 expression between CTCs and the metastatic tumor tissue was analyzed using McNemar’s test. RESULTS: For 36 evaluable patients, the specificity of HER2 on CTCs to tissue was 92.9% for PB samples collected within 5 weeks of the tumor biopsy and 100% at for PB samples collected between 5-10 weeks post biopsy, with overall concordance of 65% (independent of CTC collection time point), accuracy of 76.5% and specificity of 79.7%. A change in HER2 in amplification between the metastatic tumor and CTCs was noted in 36% (13/36) of patients with 7 patients HER2+ in tissue, HER2- on CTCs and 8 patients HER2- on tissue, HER2+ on CTCs. CONCLUSION: These data demonstrate high accuracy of HER2 amplification on CTCs at baseline and within 10 weeks of treatment and provide a sensitive and specific mechanism to monitor for changes in HER2 status that may be due to either tissue heterogeneity or receptor switch, a well-established phenomenon. This ability to effectively and contemporaneously monitor HER2 status on CTCs has the potential to identify patients who may benefit from the addition of anti-HER2 therapy and those are on anti-HER2 therapy who may not benefit optimally and for whom additional therapeutic options may warrant consideration.
Citation Format: Vered Stearns, Jennifer Lehman, Christine Mitchell, Barbara Blouw, Lan Huynh, Veena Singh. Her2 expression in matched metastatic tumor and circulating tumor cells (ctcs) in breast cancer: Implications for profiling and monitoring of her2 status to help guide anti-her2 therapy [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 PS2-14.