Purpose:

The aim of PREDICT was to confirm clinical validity and the potential for clinical utility of serial circulating tumor cell (CTC) enumeration in patients with metastatic breast cancer, focusing on its prognostic value in different breast cancer subtypes and clinical settings.

Experimental Design:

In total, 4,436 individual patient-level data with CTC results from both baseline and one follow-up (CellSearch; Menarini Silicon Biosystems) were analyzed to evaluate the association between CTC detection and overall survival (OS) in the full patient cohort and separately for tumor and treatment types.

Results:

Using the cutoff ≥1 CTC for CTC positivity, 913 (20.6%) patients had 0 CTCs at both time points (neg/neg) and 325 (7.3%) and 1,189 (26.8%) patients converted from CTC negative to CTC positive (neg/pos) or vice versa (pos/neg), whereas 2,009 (45.3%) patients had at least one CTC at both time points (pos/pos). The median OS for the neg/neg, neg/pos, pos/neg, and pos/pos group was 45.6, 26.1, 32.3, and 17.3 months, respectively (P < 0.0001, global log-rank test). CTC responders (pos/neg) showed a lower risk of death compared with CTC nonresponders (pos/pos; HR, 0.48; 95% confidence interval, 0.44–0.53). Similar results were obtained in subgroup analyses according to hormone receptor and HER2 subtype, treatment type, and with a ≥5 CTC cutoff for CTC positivity.

Conclusions:

Follow-up CTC assessments strongly predict OS independently from tumor subtype and treatment. New randomized trials to define the clinical utility of CTC monitoring for risk stratification and as an early response marker in metastatic breast cancer are urgently needed.

This content is only available via PDF.
©2025 The Authors; Published by the American Association for Cancer Research
2025
American Association for Cancer Research
This open access article is distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) license.
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License .
Attribution-NonCommercial-NoDerivatives

Article PDF first page preview

First page of Clinical Validity of Repeated Circulating Tumor Cell Enumeration as an Early Treatment Monitoring Tool for Metastatic Breast Cancer in the PREDICT Global Pooled Analysis<alt-title alt-title-type="short">Clinical Validity of Repeated CTC Enumeration in MBC</alt-title>

Supplementary data

Supplementary Methods S1

Supplementary Methods 1

- pdf file
Supplementary Table S1

Supplementary Table 1. Clinical trials, multicenter studies, and institutions/centers that provided data sets from MBC patients for the pooled analysis.

- pdf file
Supplementary Table S2

Supplementary Table 2. Absolute and relative frequencies of CTC change groups and percentage of CTC responders (as categorized according to the ≥1 CTC or ≥5 CTC cutoff for CTC positivity) overall, according to tumor subtypes and according to treatment type.

- pdf file
Supplementary Table S3

Supplementary Table 3: Comparisons of the probabilities of being CTC positive among tumor subtypes (hormone receptor-positive/HER2-negative, HER2-positive, triple-negative) according to time point of CTC assessment (baseline, first follow-up) and cutoff for CTC positivity (≥1 CTC, ≥5 CTCs). Probabilities of being CTC positive are given in terms of percentages and odds ratios with 95% confidence intervals (CI) obtained using binary logistic regression models with the response variable CTC positive (yes vs no)

- pdf file
Supplementary Table S4

Supplementary Table 4: Comparisons of the probabilities of being CTC positive betweenHER2- positive/hormone receptor-positive and HER2-positive/hormone receptor-negative tumors according to time point of CTC assessment (baseline, first follow-up) and cutoff for CTC positivity (≥1 CTC, ≥5 CTCs). Probabilities of being CTC positive are given in terms of percentages and odds ratios with 95% confidence intervals (CI) obtained using binary logistic regression models with the response variable CTC positive (yes vs no).

- pdf file
Supplementary Table S5

Supplementary Table 5: Comparisons of the probabilities of patients that are CTC positive at baseline being a CTC responder (i.e., switching from CTC positive at baseline to CTC negative at first follow-up) among tumor subtypes (hormone receptor-positive/HER2-negative, HER2-positive, triple-negative) according to cutoff for CTC positivity (≥1 CTC, ≥5 CTCs). Probabilities of being a CTC responder are given in terms of percentages and odds ratios with 95% confidence intervals (CI) obtained using binary logistic regression models with the response variable CTC responder (yes vs no).

- pdf file
Supplementary Table S6

Supplementary Table 6: Comparisons of the probabilities of patients that are CTC positive at baseline being a CTC responder (i.e., switching from CTC positive at baseline to CTC negative at first follow-up) between HER2-positive/hormone receptor-negative and HER2-positive/hormone receptor-positive tumors according to cutoff for CTC positivity (≥1 CTC, ≥5 CTCs). Probabilities of being a CTC responder are given in terms of percentages and odds ratios with 95% confidence intervals (CI) obtained using binary logistic regression models with the response variable CTC responder (yes vs no).

- pdf file
Supplementary Table S7

Supplementary Table 7. Median overall survival (OS) and hazard ratios for the CTC change groups as categorized based on the ≥5 CTC cutoff for CTC positivity (reference group neg/neg) for patients with hormone receptor-positive/HER2-negative, HER2-positive and triple-negative tumors.

- pdf file
Supplementary Table S8

Supplementary Table 8. Median overall survival (OS) and hazard ratios for the CTC change groups as categorized based on the ≥5 CTC cutoff for CTC positivity (reference group neg/neg) for patients with HER2-positive/ hormone receptor-positive and HER2-positive/ hormone receptor-negative tumors

- pdf file
Supplementary Table S9

Supplementary Table 9. Median overall survival (OS) and hazard ratios for the CTC change groups as categorized based on the ≥5 CTC cutoff for CTC positivity (reference group neg/neg) for patients that received chemotherapy-based or endocrine therapy-based treatment.

- pdf file
Supplementary Figure S1

Supplementary Figure 1. Diagram showing patient disposition.

- pdf file
Supplementary Figure S2

Supplementary Figure 2: Kaplan-Meier plots of overall survival (OS) according to CTC status at baseline for a cutoff for CTC positivity ≥1 CTC (A, B, C) and a cutoff for CTC positivity ≥5 CTCs (D, E, F). Survival time is given as time since baseline CTC assessment in months. (A, D) hormone receptor-positive/HER2-negative tumors; (B, E) HER2- positive tumors; (C, F) triple-negative tumors. The P-values refer to pairwise comparisons with the log rank test.

- pdf file
Supplementary Figure S3

Supplementary Figure 3: Kaplan-Meier plots of overall survival (OS) according to CTC status at baseline for HER2-positive/hormone receptor-positive tumors(A, B) and HER2-positive/hormone receptor-negative tumors(C, D). Survival time is given as time since baseline CTC assessment in months. (A, C) cutoff for CTC positivity ≥1 CTC; (B, D) cutoff for CTC positivity ≥5 CTCs. The P-values refer to pairwise comparisons with the log rank test.

- pdf file
Supplementary Figure S4

Supplementary Figure 4. Kaplan-Meier plot of overall survival according to change in CTC status from baseline to first follow-up (cutoff for CTC positivity ≥1 CTC). (A) HER2-positive/hormone receptor-positive tumors; (B) HER2-positive/hormone receptor-negative tumors. Survival time is given as time since baseline CTC assessment in months. The P-values refers to the global log rank test with 3 degrees of freedom.

- pdf file