Prognostic relevance of the HER2 status of circulating tumor cells in metastatic breast cancer patients screened for participation in the DETECT study program

Abstract

Background: Circulating tumor cells (CTCs) have been reported to predict clinical outcome in metastatic breast cancer (MBC). Biology of CTCs may differ from that of the primary tumor and HER2-positive CTCs are found in some patients with HER2-negative tumors. Patients and methods: Patients with HER2-negative MBC were screened for participation in DETECT III and IV trials before the initiation of a new line of therapy. Blood samples were analyzed using CELLSEARCH. CTCs were labeled with an anti-HER2 antibody and classified according to staining intensity (negative, weak, moderate, or strong staining). Results: Screening blood samples were analyzed in 1933 patients with HER2-negative MBC. As many as 1217 out of the 1933 screened patients (63.0%) had 1 CTC per 7.5 ml blood; 5 CTCs were detected in 735 patients (38.0%; range 1-35 078 CTCs, median 8 CTCs). HER2 status of CTCs was assessed in 1159 CTC-positive patients; 1 CTC with strong HER2 staining was found in 174 (15.0%) patients. The proportion of CTCs with strong HER2 staining among all CTCs of an individual patient ranged between 0.06% and 100% (mean 15.8%). Patients with estrogen receptor (ER)-and progesterone receptor (PR)-positive tumors were more likely to harbor 1 CTC with strong HER2 staining. CTC status was significantly associated with overall survival (OS). Detection of 1 CTC with strong HER2 staining was associated with shorter 3) versus 16.5 (14.9-18.1) months in patients with CTCs with negative-tomoderate HER2 staining only, P ¼ 0.013]. In multivariate analysis, age, ER status, PR status, Eastern Cooperative Oncology Group performance status, therapy line, and CTC status independently predicted OS. Conclusion: CTC detection in patients with HER2-negative disease is a strong prognostic factor. Presence of 1 CTC with strong HER2 staining was associated with shorter OS, supporting a biological role of HER2 expression on CTCs.

Circulating tumor cell assay to non-invasively evaluate PD-L1 and other therapeutic targets in multiple cancers

“…With our test, we show sensitivity of 83%, 80% and 63% and specificity of 89%, 94%, 89% for ER, PR, HER2 respectively on CTCs derived from known cancer patients. Studies have reported significant heterogeneity between ER/PR/HER2 protein expression in CTCs and primary tumor/metastatic biopsy, and this status may change over time due to therapy [11,[42][43][44][45]. In our CTC-based test, we observed slightly lower sensitivity for HER2 by ICC than other markers.…”

“…ER, PR and HER2 status is prognostic and predictive in breast cancer [41,42]. The choice of targeted therapies in breast, ovarian and uterine neoplasms depends on the expression of ER/PR on the tumor cells.…”

Heterogeneity of HER2 Expression in Circulating Tumor Cells of Patients with Breast Cancer Brain Metastases and Impact on Brain Disease Control

“…Curiously, in patients with HER2-negative metastatic breast cancer screened for participation in the DETECT study and analyzed using the CellSearch system, the presence of ≥1 CTC with strong HER2 staining was associated with a shorter OS. A possible explanation for this contrasting finding is that patients receiving HER2-directed treatment based on the detection of HER2-positive CTC were not included in the survival analysis [19]. In our study with a pragmatic approach, 38% of patients were receiving HER2-targeted therapy, which might have altered the clinical course of disease and improved the outcome for patients.…”

“…Between November 2016 and February 2018, 39 women were accrued. Patients underwent SRT with radiosurgery (SRS) or stereotactic fractionated radiotherapy (SFRT) in 68% (27) and 31% (12) of cases, respectively, with a median prescribed dose of 20 Gy (15)(16)(17)(18)(19)(20)(21)(22) with SRS and 27.5 Gy (25-30) in five fractions with SFRT.…”

Unveiling the Potential of Liquid Biopsy in HER2-Positive Breast Cancer Management

“…The CTC clearance at the end of treatment was not associated with OS, although better OS was observed in patients with no evidence of CTCs at first follow-up compared to patients with detectable CTCs (HR 0.36; 95% CI, 0.17-0.76; p = 0.005) (Table 1). Finally, in a very recent research article also within the DETECT program, the authors analysed the HER2 status of CTCs in patients HER2-negative tumours and its clinical significance [54]. Herein, CTCs HER2 status was analysed in 1159 CTCs-positive patients.…”