Prognostic and Predictive Value of Circulating and Disseminated Tumor Cells in Breast Cancer: A National Cancer Database (NCDB) Analysis

Abstract

Importance: Our understanding of the utility of circulating tumor cells (CTCs) and disseminated tumor cells (DTCs) as clinical biomarkers continues to evolve. Objective: This study evaluated (1) clinicopathologic factors associated with the presence of CTCs or DTCs, (2) the prognostic value of CTCs or DTCs by disease stage, 3), the value of these biomarkers in predicting the benefit of chemotherapy. Design: This is a retrospective analysis of patients with breast cancer (BC) diagnosed between 2004 and 2016 using the National Cancer Database (NCDB). To evaluate variables associated with the presence of CTCs or DTCs at the univariate level, we used chi-squared and Wilcoxon rank-sum tests. Multivariate logistic regression models were then constructed using significant variables. Consequently, we included CTC or DTC status (i.e. positive or negative) in multivariate, stage-by-stage Cox regression analyses for overall survival (OS). After stratifying by receptor status and staging, we used the Kaplan-Meier method to explore chemotherapy efficacy in CTC- or DTC-positive vs. CTC- or DTC-negative subsets. Results: Factors significantly associated with CTCs were race, progesterone receptor status, HER2 status, histology and AJCC N- and M-staging. Factors associated with DTCs were race, HER2 status, histology and AJCC N-staging. CTCs were associated with poor OS in late-stage (III and IV) but not early-stage (0-II) BC. DTCs were not significantly associated with OS in either context. In hormone receptor (HR)-positive disease, chemotherapy was associated with better OS when CTC status was positive, both in early-stage and late-stage disease. In a subset of patients without CTCs, however, chemotherapy conferred no survival benefit. DTC status was not a significant predictor of chemotherapy efficacy in early or late-stage, HR+ disease. Conclusions: This study suggests that CTC-status is a significant prognostic factor at later stages of BC; yet it can also help guide management of early-stage disease as it appears predictive for chemotherapy benefit.

Role of circulating tumor DNA and circulating tumor cells in breast cancer: History and updates

“…8 Tissue-based protein biomarkers such as estrogen receptor (ER), progesterone receptor (PR), HER2, and Ki67 are used to choose an appropriate treatment and estimate prognosis. 8,11 However, in locations where the cancer is surgically inaccessible, a tumor biopsy may increase the risk of metastasis. 3,12 Moreover, since neither multiple site-testing nor longitudinal testing is feasible, a tissue biopsy is not amenable for repetition.…”

“…The last disadvantage encountered with tumor biopsy is that it is expensive and time-consuming. 11 Blood-based tumor markers such as CA 15-3 and carcinoembryonic antigen (CEA) are used to monitor therapy in advanced disease. Several studies show that high levels of CA 15-3 and CEA levels act as highly accurate evidence of recurrence of BC in postoperative asymptomatic patients.…”

“…Furthermore, even though circulating biomarkers have efficiently uncovered metastasis to distant organs such as bones or liver, they have little value in characterizing locoregional metastasis or lung-only metastasis. 11 Liquid biopsy has emerged as a clinical tool that can overcome such restraints, allowing for a better representation of disease status. Since blood can be easily sampled, this approach is regarded as noninvasive and repeatable, conveying dynamic assessment of biomarkers.…”

“…ctDNA measurement allows the determination of the genetic variations accountable for the resistance to specific treatment regimens. 11 CTCs and ctDNA provide different, yet complementary information. ctDNA and CTCs have become the real-time liquid biopsy biomarkers redirecting the diagnosis, prognosis of cancers, and dynamic surveillance of cancer therapies.…”

Morphological features of breast cancer circulating tumor cells in blood after physical and biological type of isolation

“…Circulating tumor cells (CTCs) have become an important biomarker in breast cancer as they can provide critical information about disease progression and response to therapy. 1 , 2 They represent an intermediate part of the metastatic cascade, therefore monitoring CTC levels in the blood has exceptional implications for the management of cancer patients. 3 In the blood stream, CTCs are a heterogeneous cell population of tumor cells with different phenotypes.…”