Presence of CTCs 2 years post chemotherapy linked to poorer survival

 SAN ANTONIO — The presence of circulating tumor cells during long-term follow-up independently predicted poorer survival among women with high-risk early breast cancer, according to data from the phase 3 SUCCESS A trial presented at the San Antonio Breast Cancer Symposium.

Circulating tumor cells (CTCs) can be detected in approximately 20% of patients with early breast cancer and 60% of patients with advanced breast cancer, Wolfgang Janni, MD, PhD, director of the department of obstetrics and gynecology at University of Ulm in Germany, said during his presentation. Further, level one evidence has indicated CTCs are an independent prognostic marker in primary and metastatic disease.

“CTCs and monitoring of those has been established as an early surrogate marker for treatment response in advanced breast cancer and is available throughout all points of time of the disease,” Janni said. “However, up to now, no data has been available regarding the prognostic role of CTCs during long-term follow-up of breast cancer.”

The SUCCESS A trial included 3,754 patients with high-risk disease who were randomly assigned to receive adjuvant chemotherapy with 3 cycles of epirubicin-fluorouracil-cyclophosphamide followed by 3 cycles of docetaxel alone or with gemcitabine. Researchers also randomly assigned patients to receive 2 or 5 years of treatment with zoledronate.

Janni and colleagues evaluated data from 1,087 women (median age, 53 years; range, 21-76) who had evaluable CTC data using the CellSearch System (Janssen).

Median follow-up from day of randomization to CTC assessment was 28.4 months. Median follow-up was 37 months thereafter.

Overall, researchers observed a positive CTC status — defined as at least one CTC in 7.5 mL of whole blood — in 204 of these patients 2 years post chemotherapy.

There were no associations between CTC status and patient and primary tumor characteristics and locoregional and systemic treatment.

In multivariate analyses adjusted for factors such as age, menopausal status, tumor size and CTC status before chemotherapy, the presence of CTCs 2 years post chemotherapy appeared significantly associated with increased risk for poor OS (HR = 3.82; 95% CI, 1.99-7.31) and DFS (HR = 2.28; 95% CI, 1.48-3.5).

Seven hundred nineteen patients (65.2%) were CTC negative before and 2 years after chemotherapy, whereas 157 patients (14.2%) were CTC negative prior to chemotherapy but CTC positive 2 years post chemotherapy. Conversely, 180 patients (16.3%) who were CTC positive prior to chemotherapy achieved CTC-negative status 2 years later. There were 47 patients (4.3%) who had persistently positive CTC levels.

Among these four cohorts, researchers observed significant differences in OS and DFS (P ˂ .0001 for both). However, the cohort with persistent CTCs had the poorest survival outcomes.

Only the HER-2–positive subtype showed no association with CTC status and subsequent DFS and OS, but this did not reach statistical significance, Janni said.

“Based upon this, we hypothesize monitoring of minimal residual disease might be helpful as a surveillance tool to identify breast cancer patients at high risk for relapse who could benefit from tailored intensified follow-up or secondary treatment intervention,” Janni said.

The Treat-CTC-Study — an EORTC and BIG intergroup study — will compare additional treatment with trastuzumab (Herceptin, Genentech) vs. no further treatment among patients with persistent CTCs after chemotherapy, Janni said. – by Alexandra Todak

Reference: Janni W, et al. Abstract S2-03. Presented at: San Antonio Breast Cancer Symposium; Dec. 8-12, 2015; San Antonio.

Disclosure: Janni and other study researchers report financial relationships with AstraZeneca, Chugai, Janssen, Lilly, Novartis and Sanofi.