Liquid biopsy as a surveillance tool for breast cancer follow-Up

in Commentary November 26, 2018

from Cancer Therapy Advisor by Christina Bennett

Patients with high-risk early-stage breast cancer with detectable circulating tumor cells (CTCs) 2 years after chemotherapy completion had worse survival and greater risk of disease recurrence compared with patients without detectable CTCs, a study published in the Journal of the National Cancer Institute found.¹ These findings come shortly after Sparano and colleagues reported a similar correlation between the presence of CTCs and risk of recurrence in patients with estrogen receptor-positive breast cancer.²

“Usually we are only able to determine the prognosis of our patients based on tumor biology and patient characteristics,” study coauthor Elisabeth Trapp, MD, department of gynecology and obstetrics, Ludwig-Maximilians-University Munich, Germany, told Cancer Therapy Advisor. “Using liquid biopsy will help us to answer the question in a more individualized and patient-targeted way. These are preliminary data showing that liquid biopsy may be used as a sort of surveillance tool throughout breast cancer follow-up.”

The results are based on data from the SUCCESS A trial (ClinicalTrials.gov Identifier: NCT02181101), a multicenter, open-label, phase 3 randomized study that evaluated 2 adjuvant chemotherapy regimens followed by 2 years or 5 years of zoledronate in patients with high-risk early-stage breast cancer.

Investigators used the CellSearch system, which has been approved by the US Food and Drug Administration, to screen for CTCs both at baseline and at 2 years after the completion of chemotherapy. A positive CTC detection was defined as the presence of at least 1 CTC in 7.5 mL of peripheral blood. Overall survival and disease-free survival were also assessed at 2 years after chemotherapy; survival included death from any cause.

In total, 1087 patients with high-risk early-stage breast cancer were included in the analysis, and at 2 years after chemotherapy completion, 198 patients (18.2%) had detectable CTCs.

Patients with detectable CTCs at 2-year follow-up had a nearly 4-fold elevated risk of death and more than 2-fold greater risk of disease recurrence compared to patients without detectable CTCs. Broken down, of the patients who were CTC-positive at follow-up, 10.6% (21 of 198) died and 18.2% (36 of 198) had disease recurrence. Of the patients who were CTC-negative at follow-up, 2.5% (22 of 889) died and 7.3% (65 of 889) had disease recurrence.

“We have a couple trials now that show this,” Julie Gralow, MD, told Cancer Therapy Advisor, referring to Trapp et al and Sparano et al. Dr Gralow is the director of breast medical oncology at Seattle Cancer Care Alliance, Washington. She was not involved in the current study. Now the real question, she said, is whether a treatment can be given at this time point to reduce the risk of recurrence.

Case in point, an exploratory subgroup analysis in the Trapp et al study found that 10 of 39 triple-negative breast cancer patients with CTC positivity (25.6%) had recurrence. For triple-negative patients that are CTC positive at follow-up, Dr Gralow postulated, would you give chemotherapy at that point when three quarters of patients won’t recur and a quarter will? Patients who have triple-negative breast cancer currently don’t have many FDA-approved therapy options besides chemotherapy.

“That’s something that we’d have to do a trial [to know] and hopefully it wouldn’t be that we’d give chemo again years down the line,” she said, “but we’d have some other targeted therapy that could be oral and less toxic.”

A trial called LATER-R that may provide insights into possible interventions is in the very early stages of planning. The trial is being developed by Joseph Sparano, MD, at Montefiore Medical Center, New York, and his colleagues.

Dr Trapp welcomed further study, saying, “A prospective randomized follow-up trial on liquid biopsy is required to validate its power to identify patients with a high risk for recurrence.”

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