Circulating tumor cells - not serum tumor markers - predict survival in metastatic breast cancer

Abstract

9516 Background: The presence of ≥5 circulating tumor cells (CTCs) in 7.5mL of blood in women with metastatic breast cancer (MBC) is associated with poor outcome (NEJM 2004). Here we provide previously unreported data from this multi-center trial on the assessment of the serum tumor marker MUC-1 (CA27.29 and/or CA15–3). Methods: In 65 of 177 MBC patients CTCs were assessed at 1st follow-up and MUC-1 at baseline, 1st follow-up (n=65), and the first disease reassessment (V1) after initiation of therapy (n=54). Assessment of MUC-1 was not mandated by the protocol and was only available from investigators that performed the assay as part of their routine assessment. CTCs were immunomagnetically separated and fluorescently labeled using the CellSearch Kit. Only nucleated (DAPI+) cells with the phenotype EpCAM+, Cytokeratin 8, 18 and/or 19+, and CD45- were counted using the CellSpotter Analyzer. Patients were classified as positive when ≥5 CTCs/7.5mL were detected. Patients were classified as positive when MUC-1 increased by 25% over the two time points. Results: Twenty-four of 65 (37%) patients had ≥ 5CTCs, 19 of 65 (29%) and 18 of 54 (33%) had >25% increase in MUC-1 at 1st follow-up and V1 respectively. CTCs and change in MUC-1 did not significantly correlate at any time point. In a univariate Cox hazards regression analysis, significant parameters for Progression Free Survival (PFS) were type of therapy (p=0.0197), change in MUC-1 (p≤0.0008), and CTCs (p=0.0008). For Overall Survival (OS) significant parameters were ER/PR (p=0.0172), ECOG (p=0.0128), type of therapy (p=0.0314) and CTCs (p=0.0064). MUC-1 was not significant for OS at 1st follow-up or 1st disease reassessment (p≥0.2255). In multivariate analyses, CTCs remained the strongest and most significant independent predictor of poor outcome. Conclusions: A significant correlation between PFS and change in serum MUC-1 tumor marker and CTCs was found in MBC. MUC-1 however did not correlate with overall survival. The presence of CTCs after initiation of therapy strongly correlates with survival and may be a more appropriate surrogate measure of disease progression. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Immunicon Immunicon