The Value of Monitoring the Behavior of Circulating Tumor Cells at the End of Endocrine Therapy in Breast Cancer Patients

Katharina Pachmann,Stefan Schuster

doi:10.3390/cancers10110407

Abstract

After five years of endocrine therapy, patients with ER+ (estrogen receptor positive) breast cancer face the question of the benefit of further treatment. Ten years of endocrine therapy has been demonstrated to improve survival compared to five years. However, the individual benefit of continuation remains unclear. Therefore, markers for predicting benefit from endocrine treatment and extended endocrine treatment are desperately needed. In this study the dynamics over time of the tumor cells circulating in peripheral blood of patients, circulating tumor cells/ circulating epithelial tumor cells (CTC/CETC), as the systemic part of the tumor were investigated in 36 patients with ER+ primary breast cancer. CTC/CETCs were monitored serially during and after endocrine therapy. After termination of endocrine therapy 12 patients showed an increase in CTC/CETCs, with 8 of 12 suffering relapse. No change or a reduction was observed in 24 patients, with 2 of 24 suffering relapse. Initial tumor size was marginally prognostic (p = 0.053) but not nodal status nor the mere number of CTC/CETCs. Only the trajectory of CTC/CETCs was a statistically significant predictor of relapse free survival (increasing cell numbers: mean = 940 days vs. stable/decreasing cell numbers mean not reached). Individual cases demonstrated that an increase of CTC/CETCs after discontinuation of tamoxifen therapy could be stopped by resuming the endocrine therapy.

Highlights

Until recently adjuvant chemotherapy was given to almost all primary breast cancer patients in order to prevent metastasis formation [1]
In this study the dynamics over time of the tumor cells circulating in peripheral blood of patients, circulating tumor cells/ circulating epithelial tumor cells (CTC/CETC), as the systemic part of the tumor were investigated in 36 patients with ER+ primary breast cancer
We show that an increase in cell numbers after the end of endocrine treatment is of highly significant clinical relevance but that auptake of therapy can lead to re-decreasing CETC

Summary

Introduction

Until recently adjuvant chemotherapy was given to almost all primary breast cancer patients in order to prevent metastasis formation [1]. Since most chemotherapeutic agents are mainly active against proliferating cells it has long been known that this leads to overtreatment, especially in patients that have estrogen receptor positive breast cancer with a low fraction of proliferating cells [2]. Expression analyses from the primary tumor comprising genes which are involved in multiple cellular and cancer-associated processes such as cell cycle, proliferation, invasion, angiogenesis, and metastasis formation [3,4] were developed and the term precision oncology was used to describe the selection or deselection of adjuvant chemotherapy guided by these expression profiling tools. There is still no consensus as to whether these new tools will definitely be helpful. It remains the decision of the patient who may mull for years over whether she has made the right decision

Methods

Results

Conclusion