The prognostic impact of circulating tumor cells in subtypes of metastatic breast cancer

Abstract

The detection of circulating tumor cells (CTCs) in the peripheral blood of metastatic breast cancer (MBC) patients is an independent marker of prognosis. This large prospective multicenter study aimed to assess the impact of CTCs on overall survival (OS) and progression free survival (PFS) in patients with predefined molecular subgroups of MBC. To this end, 468 MBC patients were divided into three subgroups based on immunohistochemical staining of the primary tumor: (1) hormone receptor-positive/HER2-negative (HorR+/HER2-), (2) HER2-positive (HER2+), and (3) HorR-negative/HER2-negative (HorR-/HER2-) patients. CTC status (<5 CTCs/7.5 ml blood (CTC-negative) vs. ≥5 CTCs/7.5 ml blood (CTC-positive)) was determined using the CellCearch(®) system before patients started a new line of therapy. At baseline, 205 (42 %) patients were CTC-positive. On multivariate analysis, CTC-positivity was an independent prognostic factor for shorter PFS and OS. In HorR+/HER2- patients, median PFS [95 % CI] of CTC-negative versus CTC-positive patients was 8.60 [5.93-11.27] versus 4.33 [3.29-5.38] months (p < 0.001), in HER2+ patients 7.60 [5.40-9.79] versus 6.60 [4.20-9.00] months (p = 0.477) and in HorR-/HER2- patients 5.83 [5.09-6.78] versus 3.05 [1.81-4.29] months (p < 0.001), respectively. Median OS [95 % CI] of CTC-negative versus CTC-positive patients was as follows: not reached by either in the HorR+/HER2- subgroup (p < 0.001), not reached versus 18.07 [11.10-25.05] months (p = 0.001) in the HER2+ subgroup, and not reached versus 8.57 [4.07-13.07] months in the HorR-/HER2- subgroup (p = 0.001). In conclusion, our results strongly confirm the independent prognostic value of CTC enumeration in MBC patients. In contrast to recent reports, there was no association between primary tumor-based molecular subgroups and the impact of CTC status on OS. Hence, CTC status may help to identify patients who require aggressive therapy, especially among those with triple-negative MBC.

Detection of Circulating Tumor Cells in Breast Cancer Patients: Prognostic Predictive Role

“…In a larger study, 468 MBC patients were divided into three subgroups based on immunohistochemical staining of the primary tumor: hormone receptor postive, Her2-positive and triple negative groups. This study confirmed independent prognostic value of CTC detection but lack to show difference between primary tumor-based molecular subgroups and impact of CTC status on survival (Wallwiener et al, 2013). Circulating cell-free DNA carrying tumor-specific alterations (circulating tumor DNA) has been investigated and compared with cancer antigen 15-3 (CA 15-3) and circulating tumor cells in a recent study (Dawson et, al., 2013).…”

Pooled Analysis of the Prognostic Relevance of Circulating Tumor Cells in Primary Breast Cancer

“…Numerous published studies demonstrate that CTC prevalence predicts disease recurrence and survival in patients with metastatic breast cancer (MBC; refs. [2][3][4][5][6], and the persistence of CTCs after treatment has been shown to predict lack of responses to therapy in metastatic settings (7)(8)(9).…”

Role of Circulating Tumor Cells and Cell-Free Tumor Deoxyribonucleic Acid Fragments as Liquid Biopsy Materials in Breast Oncology

“…[19,20] The prognostic value of this cutoff value has been further verified by several studies and still in utilization. [21,22] Besides the prognostic role of CTC status, alteration in CTC levels during treatment has also been shown to reflect therapy response in metastatic BC. The study of Hayes et al indicated that, a decrease in CTC levels under the threshold of five-cells/7.5 ml PB predicted better PFS and OS in metastatic BC.…”

“…The dynamic individual mutations can be detected by using former approach, but it requires of specific CTC types on patient survival have contradictory results. For example, while one study determined that patients with HER2-positive CTCs had significantly longer PFS, [22] another study showed that patients with HER2-positive CTCs had significantly worse survival; [25] and another study determined that HER2 status of CTCs in metastatic BC had no correlation with clinical outcome. [26] An ongoing clinical trial called DETECT may provide results to resolve this enigma.…”