Circulating tumor cells could be used to stratify patients with hormone receptor (HR)–positive, HER2-negative breast cancer for late recurrence risk, results of a secondary analysis of a randomized clinical trial suggest.
Risk of late clinical recurrence was about 13-fold higher among HR-positive patients with a positive circulating tumor cell (CTC) assay result, according to results of the study, published in.
“This prospectively conducted study offers a high level of evidence supporting the association between a positive CTC assay result and risk of clinical recurrence,” said, of Albert Einstein College of Medicine, New York, and his coauthors.
The present study is the first to show that this CTC assay may play a role in determining late clinical recurrence after local and systemic adjuvant therapy, according to the investigators.
The study is a secondary analysis of E5103, a phase 3 trial of adjuvant doxorubicin and cyclophosphamide followed by paclitaxel with bevacizumab in patients with HER2-negative stage II-III breast cancer. Investigators included a total of 547 patients who had no clinical evidence of recurrence between 4.5 and 7.5 years of registration in that trial.
Positive CTC assay results occurred in 26 of those patients (4.8%), they found.
At a median follow-up of 2.6 years, 24 patients had a clinical recurrence, including 23 HR-positive patients and just 1 HR-negative patient. Accordingly, the investigators focused most of their further analysis on the HR-positive subset.
A total of 7 of 23 patients with HR-positive disease (30.4%) had a positive CTC assay result.
A positive CTC result in HR-positive patients was associated with a 13.1-fold increased risk of recurrence, multivariate analysis showed.
Higher CTC burden appeared to be associated with a numerically higher recurrence risk in HR-positive patients, the investigators found. They saw recurrences in 16 of 335 patients with a CTC count of 0 cells per 7.5 mL blood (4.8%), compared with 2 of 12 patients with 1 cell per 7.5 mL blood (16.7%), and 5 of 6 patients with 2 or more cells per 7.5 mL (83.3%).
Taken together, these results provided proof of concept to support additional investigations of the CTC assay and other blood-based biomarker tests in the setting of late clinical recurrence in HR-positive patients, the researchers said.
They acknowledged several limitations of this study: It was small, it had relatively short follow-up, and it did not evaluate the CTC assay in the context of other assays.
“Notwithstanding proof of concept, further evaluation is required to confirm the clinical validity and determine the clinical utility of performing the CTC assay in this context,” Dr. Sparano and his coauthors wrote.
Late recurrences, or those that occur more than 5 years after diagnosis, account for about half of all recurrences among HR-positive receptive breast cancers, Dr. Sparano and his colleagues said.
The researchers had no conflicts of interest to report. The study was supported by grants from the National Cancer Institute, National Institutes of Health, Breast Cancer Research Foundation, and Susan G. Komen Foundation.
SOURCE: Sparano J et al. JAMA Oncol. 2018 Jul 26. doi: 10.1001/jamaoncol.2018.2574.