Abstract P2-01-02: Heterogeneity and variability of human epidermal growth factor receptor 2 (HER2) expression on circulating tumor cells (CTC) in HER2 negative metastatic breast cancer patients treated with first line weekly paclitaxel and bevacizumab in a prospective cohort from the French Breast Cancer InterGroup Unicancer (UCBG): COMET study
Authors: Pierga J-Y , Proudon C , Tredan O , Decraene C , Dubot C , Lorgis V , Jacot W , Goncalves A , Debled M , Levy C , Ferrero J-M , Jouannaud C , Luporsi E , Mouret-Reynier M-A , Dalenc F , Lemonnier J , Berger F , Bidard F-C 
Published: February 2018

Abstract
Background: It has been reported in women with advanced estrogen-receptor (ER)-positive/(HER2)-negative breast cancer the acquisition of a HER2-positive CTC subpopulation during therapy (Jordan NV Nature 2016). The clinical significance of acquired HER2 heterogeneity during the evolution of metastatic breast cancer is unknown. We report here the analysis of HER2 status of CTC before and after one cycle of treatment in HER2 negative metastatic breast cancer patients treated with first line weekly paclitaxel and bevacizumab.
Patients & methods:The French cohort COMET is a prospective study including first line HER2 negative patients (pts) receiving weekly paclitaxel and bevacizumab according to EMA approved combination. The aim of this cohort is to evaluate clinical, biological and radiological parameters associated with pts outcome. We confirmed previously the outcome of patients with high CTC count at base line and after one cycle of treatment (Bidard et al, Lancet Oncol 2014). We present here the analysis on 203 pts evaluated for the expression of HER2 on CTC using the FDA cleared CellSearch method. The HER2 expression of CTCs (CB11 clone) was categorized (class 0–3) as described by Riethdorf et al.CCR2010.
Results: At base line, 144 out of 203 pts had at least one detectable CTC (71%), (median 4, and range 1- 30,000). Among them, 104 (72%) had one or more HER2 positive CTC (1-21,484). In 25 patients with HER2 2+ primary tumor with FISH or CISH non amplified, the incidence of CTC HER2+ cases (13/25, 52%) was similar than in pts with HER2 0 or HER2 1+ (51%) primary tumor. In each case, 3 to 100% of detectable CTC could be HER2+ stained (median 50% of CTC). Only 12 cases (8% of all CTC cases) had 2+ HER2 staining score on CTC and none 3+. After one cycle of treatment, the number of pts with detectable CTC dropped to 64, including 42 with HER2+ CTC (65%). Out of these cases, 14 were 3+ or 2+ HER2 score (22% of CTC+ cases). This was a significant increase compared to baseline (8%) (p&lt;0.001), including 6 cases with 100% of HER2+ CTC. To note, 7 patients without HER2+ CTC at baseline, had detectable HER2+ CTC after one cycle of treatment. With a median follow-up of 2 years, correlation of CTC variations with pts outcome is planned.
Conclusion: HER2 staining on CTC was heterogeneous with HER2 positive and negative subpopulations in the same patient with primary HER2 negative breast cancer. We observe a variability of HER2 CTC status with an increased intensity or appearance of immunostaining in few cases during treatment. We hypothesize that these phenotypes changes within patient-derived circulating tumor cells could contribute to progression of breast cancer and acquisition of drug resistance.
Citation Format: Pierga J-Y, Proudon C, Tredan O, Decraene C, Dubot C, Lorgis V, Jacot W, Goncalves A, Debled M, Levy C, Ferrero J-M, Jouannaud C, Luporsi E, Mouret-Reynier M-A, Dalenc F, Lemonnier J, Berger F, Bidard F-C. Heterogeneity and variability of human epidermal growth factor receptor 2 (HER2) expression on circulating tumor cells (CTC) in HER2 negative metastatic breast cancer patients treated with first line weekly paclitaxel and bevacizumab in a prospective cohort from the French Breast Cancer InterGroup Unicancer (UCBG): COMET study [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P2-01-02.