Prognostic and predictive effects of circulating and disseminated tumor cells in breast cancer: A National Cancer Database (NCDB) analysis.

Abstract

1029 Background: Alongside other biomarkers, circulating tumor cells (CTCs) and disseminated tumor cells (DTCs) could contribute to our growing understanding of the breast cancer (BC) “liquid biopsy”. This study evaluated 1) clinicopathologic factors associated with CTCs and DTCs, 2) the prognostic value of CTCs and DTCs by disease stage, 3), the efficacy of chemotherapy by CTC and DTC status. Methods: We conducted a retrospective analysis of BC using the 2004-2016 National Cancer Database (NCDB). The NCDB defines CTCs as isolated tumor cells (ITCs) found in the blood (using assays such as reverse transcriptase polymerase chain reaction or immunohistochemistry) distant from the breast. DTCs are ITCs found in the bone marrow or other non-regional tissues. To evaluate variables associated with CTCs or DTCs, we used chi-squared and Wilcoxon rank-sum tests (univariate), followed by multivariate logistic regression. Consequently, we included CTC or DTC status in a multivariate, stage-by-stage Cox regression analysis for overall survival (OS). After adjusting for 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: 4,846 cases reported CTC-status, 1,454 (21.1%) of which were positive. 4,993 cases reported DTC-status, 1,400 (20.3%) of which were positive. Factors associated with positive CTC status were HER2-positivity, progesterone receptor-positivity, lobular histology and N-staging. Factors associated with positive DTC status were being White, HER2-positivity, lobular histology and N-staging. Positive CTC-status was associated with poor OS overall in late-stage (III and IV) (HR 1.477, 95% CI: 1.129-1.931, p = 0.004) but not early-stage BC (0, I, II) (p = 0.110) disease. DTC-status was not associated with OS in early-stage or late-stage subsets. In hormone receptor (HR)-positive disease, chemotherapy was associated with better OS when CTC-status was also positive both in early-stage (p = 0.003) and late-stage (p = 0.023) disease. In a subset of the same BC subtype with negative CTC-status, however, chemotherapy conferred no survival benefit (p = 0.638 for early-stage, p = 0.501 for late-stage). 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 stronger 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.