Correlation of Circulating Tumor Cells with Clinicopathological Factors and Treatment Response in MBC

Circulating tumor cell (CTC) characterization for relevant biomarkers has potential clinical utility for treatment monitoring, with the goal of guiding treatment decisions. The IMAGE-II (Individualized Molecular Analyses Guide Efforts in Breast Cancer; NCT02965755) study assessed CTC detection rate, and correlated CTC levels with clinical characteristics, pathological characteristics, molecular biomarkers, and treatment response in patients with metastatic breast cancer (MBC).

The IMAGE-II study enrolled patients with MBC who progressed on at least 1 line of therapy. Archival tissue was obtained from all patients, and serial blood samples were prospectively collected for CTC analysis at various timepoints (at baseline [Day 1], after 1-2 weeks of therapy, after 8-12 weeks, and at subsequent restaging [every 8-12 weeks]). Medical record review was conducted every 3 months for ongoing treatment response and death. CTC characterization was performed for ER, HER2, and PD-L1, biomarker status.

Median age of the patient cohort was 56 years; the majority of women were non-Hispanic (94.3%), post-menopausal (52.9%), had ductal carcinoma (77.1%), and ER+/HER2- disease (58.6%). Patients had received a median of 3 prior lines of therapy.

CTC was detected in the majority of patients (84%; 59/70); of these, 63% had baseline CTC counts <5/7.5 mL; Median CTC count was 6.5. Lobular cancers and CTC-based ER+ status are associated with higher CTC levels. There was a trend for higher CTC counts at baseline in younger patients (aged <50 years vs ≥50 years), Black women, and in patients with visceral metastasis (vs non-visceral metastasis); however, these did not reach statistical significance.

Baseline CTC levels had prognostic value; higher baseline CTC levels was associated with poorer OS, which was independent of subtype, and whether they received chemotherapy or endocrine therapy. Moreover, treatment was associated with changes in CTC levels; increased CTC levels correlated with unfavorable PFS and OS, particularly in TNBC.

Significant discordance was noted between tissue-based breast cancer subtype and biomarker status by CTC analysis, with higher discordance in classification noted in expression of ER. In the HER2 cohort, 4 CTC-based HER2+ cases were CTC-based HER- and 2 CTC-based HER2- cases were CTC-based HER; these differences were not statistically significant.

In conclusion, the authors reported significant differences in the expression of ER between tumor tissue and CTC, which was attributed to tumor evolution.


Bayable A, Wang T, Blackford A, et al. Novel correlation of circulating tumor cells (CTC) with clinical characteristics, pathological factors, and treatment response in patients with metastatic breast cancer (MBC). Presented at the 46th San Antonio Breast Cancer Symposium Annual Meeting, December 5-9, 2023; San Antonio, TX: Abstract PO1-16-02.

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