Circulating tumor cell (CTC) clusters had little, if any, prognostic significance in patients with metastatic breast cancer initiating first-line chemotherapy, according to a study published in Clinical Cancer Research.1

A prospective-retrospective study of data from the SWOG0500 clinical trial tested for the number of CTCs, doublets, and clusters in 564 patients with metastatic breast cancer.

Patients were classified into 3 prognostic subgroups based on baseline CTC/7.5 mL whole blood. Arm A was patients with less than 5 CTCs (273 individuals). Arm B was patients with 5 or more CTCs and then less than 5 CTCs at first follow-up (160 individuals). Arm C was patients with 5 or more CTCs at baseline and first follow-up (n=116).

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About 1 in 5 patients (19%) had CTC doublets or clusters at baseline. Patients in arm B or arm C were significantly more likely to have doublets or clusters than patients in arm A (38% vs. 1.4%; P<.0001). Doublets and clusters were also twice as common in patients in arm C compared with arm B (54% vs. 25%; P<.0001).

Survival analysis showed that patients in arm B or arm C with doublets and clusters at baseline had significantly worse overall survival (11.7 months) compared with doublets only (16.8 months) or clusters only (22.9 months) or no doublets or clusters (19.9 months; P =.008). Looking only at patients assigned to arm B, there was no significant difference in overall survival between patients with doublets and clusters compared with patients with only doublets or those with neither.

Compared with enumeration of CTCs alone, presence of doublets, clusters, or both were not prognostic in patients who had 5 to 19 or 20 or more CTCs/7.5 mL whole blood at baseline.

“The results of this translational medicine study suggest that neither doublets nor clusters plays a major role in the outcome of MBC patients starting first line chemotherapy, raising questions regarding their role in progression of metastatic disease,” the researchers wrote. “Rather, our data suggest that absolute number of CTC[s] may be more important than the physical presence of clusters.”


Paoletti C, Miao J, Dolce EM, et al. Circulating tumor cell clusters in metastatic breast cancer patients: a SWOG S0500 translational medicine study [published online July 29, 2019]. Clin Can Research. doi: 10.1158/1078-0432.CCR-19-0208