Increased Circulating Epithelial Tumor Cells (CETC/CTC) over the Course of Adjuvant Radiotherapy Is a Predictor of Less Favorable Outcome in Patients with Early-Stage Breast Cancer

Matthias Mäurer; Dorothea Schott; Monika Pizon; Sonia Drozdz; Thomas Wendt; Andrea Wittig; Katharina Pachmann

doi:10.3390/curroncol30010021

Increased Circulating Epithelial Tumor Cells (CETC/CTC) over the Course of Adjuvant Radiotherapy Is a Predictor of Less Favorable Outcome in Patients with Early-Stage Breast Cancer

Curr Oncol. 2022 Dec 24;30(1):261-273. doi: 10.3390/curroncol30010021.

Authors

Matthias Mäurer^{1

2}, Dorothea Schott³, Monika Pizon³, Sonia Drozdz¹, Thomas Wendt¹, Andrea Wittig¹, Katharina Pachmann³

Affiliations

¹ Department of Radiotherapy and Radiation Oncology, University Hospital Jena, Bachstraße 18, 07743 Jena, Germany.
² Clinician Scientist Program OrganAge, Interdisciplinary Center for Clinical Research (IZKF), Jena University Hospital, 07747 Jena, Germany.
³ Transfusionsmedizinisches Zentrum Bayreuth, Kurpromenade 2, 95448 Bayreuth, Germany.

Abstract

Background: Adjuvant radiotherapy (RT) is an integral component of a multidisciplinary treatment strategy for early-stage breast cancer. It significantly reduces the incidence of loco-regional recurrence but also of distant events. Distant events are due to tumor cells disseminated from the primary tumor into lymphatic fluid or blood, circulating epithelial tumor cells (CETC/CTC), which can reach distant tissues and regrow into metastases. The purpose of this study is to determine changes in the number of CETC/CTC in the course of adjuvant RT, and to evaluate whether they are correlated to local recurrence and distant metastases in breast cancer patients.

Methods: Blood from 165 patients irradiated between 2002 and 2012 was analyzed 0-6 weeks prior to and 0-6 weeks after RT using the maintrac^® method, and patients were followed over a median period of 8.97 (1.16-19.09) years.

Results: Patients with an increase in CETC/CTC numbers over the course of adjuvant RT had a significantly worse disease-free survival (p = 0.004) than patients with stable or decreasing CETC/CTC numbers. CETC/CTC behavior was the most important factor in predicting subsequent relapse-free survival. In particular, patients who had received neoadjuvant chemotherapy were disproportionately more likely to develop metastases when cell counts increased over the course of RT (p = 0.003; hazard ratio 4.886).

Conclusions: Using the maintrac^® method, CETC/CTC were detected in almost all breast cancer patients after surgery. The increase in CETC/CTC numbers over the course of RT represents a potential predictive biomarker to judge relative risk/benefit in patients with early breast cancer. The results of this study highlight the need for prospective clinical trials on CETC/CTC status as a predictive criterion and for individualization of treatment.

Clinical trial registration: The trial is registered (2 May 2019) at trials.gov under NCT03935802.

Keywords: biomarkers; circulating epithelial tumor cells; early-stage breast cancer; prediction; radiotherapy.

Publication types

Clinical Trial
Research Support, Non-U.S. Gov't

MeSH terms

Breast Neoplasms* / drug therapy
Carcinoma*
Female
Humans
Prospective Studies
Radiotherapy, Adjuvant

Substances

bis(beta-carboxyethyl)tin dichloride

Associated data

ClinicalTrials.gov/NCT03935802

Grants and funding

M.M. was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) Clinician Scientist Program OrganAge (funding number 413668513) and by the Interdisciplinary Center of Clinical Research of the Medical Faculty Jena.