Two Years After Chemotherapy, Circulating Tumor Cells are Harbingers of Shorter Survival

SAN ANTONIO—Circulating tumor cells (CTCs) 2 years after chemotherapy are associated with poor survival rates among patients with high-risk, early-stage breast cancer, according to an analysis of data from the randomized, open-label phase 3 SUCCESS A trial. The findings were presented at the 2015 San Antonio Breast Cancer Symposium.¹

“The presence of CTCs as assessed during routine breast cancer follow-up care 2 years after adjuvant chemotherapy was associated with poor survival,” reported lead author Wolfgang Janni, MD, PhD, of University Hospital Ulm in Germany. “Monitoring of minimal residual disease, such as CTC testing, during breast cancer follow-up might be used as a surveillance marker to identify patients at high risk for relapse who could benefit from tailored intensified follow-up care and/or secondary treatment intervention.”

CTCs are believed to be prognostic in early and metastatic breast cancer, noted Dr Janni. However, there has been scant data available regarding the prognostic role of CTCs assessed during long-term follow-up care.

The research team therefore sought to assess the prognostic value of CTCs 2 years after chemotherapy from the SUCCESS A phase 3 trial. High-risk breast cancer patients were randomly assigned to recieve adjuvant chemotherapy treatment with 3 cycles of epirubicin-fluorouracil-cyclophosphamide followed by either 3 cycles of docetaxel or 3 cycles of gemcitabine-docetaxel. After that treatment patients were then randomly assigned to undergo either 2 or 5 years of zoledronate treatment.

Using the FDA-approved CellSearch System (Janssen Diagnostics, LLC), the researchers defined CTC positivity as 1 or more circulating tumor cell captured from 21 mL of peripheral blood.

After initial univariate analyses, survival times were analyzed in multivariate regression tests “adjusting for age, menopausal status, tumor stage, nodal stage, grading, histological type, hormone receptor status and HER2 status,” he said. Survival times were measured beginning with the date of follow-up CTC assessment two years after chemotherapy.

A total of 198 (18.2%) of 1087 patients had positive CTC status 2 years after adjuvant chemotherapy, Dr Janni reported.

“Presence of CTCs 2 years after adjuvant chemotherapy is a significant independent prognostic factor for poor overall survival and poor disease-free survival,” Dr Janni concluded. “The prognostic value of the presence of CTCs 2 years after chemotherapy was not evident for patients with HER2-positive tumors.” However, there was no statistical interaction between biological subtype and CTC presence.

Multivariate analysis of CTC status before chemotherapy “showed significant independent prognostic role for CTC status 2 years after chemotherapy on overall survival (OS; hazard ratio (HR) 3.82, 95% confidence interval (CI) 1.99-7.31; P <.001) and disease-free survival (DFS; HR 2.28, 95% CI 1.48-3.50, P < .001),” Dr Janni concluded.

Reference

1. Janni W, Rack B, Fasching P, et al. Persistence of circulating tumor cells in high risk early breast cancer patients during follow-up care suggests poor prognosis – Results from the adjuvant SUCCESS A trial. Oral presentation at: San Antonio Breast Cancer Symposium 2015; December 9, 2015; San Antonio, TX.