Abstract PD04-03: Circulating Tumor Cells as Predictor of Metastatic Disease Spread in Patients with Breast Cancer

Abstract

Abstract Background. The formation of distant metastases in each tissue is a tightly regulated biological event. The characteristic organ distribution of metastasis in the various cancers was first recognized in 1889 by Paget and gave rise to the “ seed and soil “ hypothesis. Several reports demonstrate that the presence of more than 5 circulating tumor cells (CTC) in peripheral blood is associated with short survival in patients (pts) with metastatic breast cancer (MBC). Interestingly, pts with bone metastasis had higher absolute number and percentage of ≥5 CTC (De Giorgi et al. 2010). Because of the correlation between CTC detection, metastatic site and prognosis, we hypothesized that the baseline detection of ≥5 CTC at the time of initial recurrence can predict the development of new metastatic sites, when progression of disease occurs. Methods. We retrospectively evaluated a cohort of 516 MBC pts who had a CTC assessment before starting systemic treatment at the M.D. Anderson Cancer Center between September 2004 and November 2009. CTC were enumerated using the CellSearch™ technology. Among all pts, we selected 408 women with documented radiological progression of disease defined according to RECIST. Pts were divided in 2 categories: subjects who experienced progression of the pre-existing metastatic site(s) and those who developed new metastatic site(s). The rate of development of new metastatic sites was compared between groups according to baseline value of CTC (<5 vs of ≥5), by Fisher Exact Test. Results. At a median follow-up of 16 months (range, 1-58), 168 (41%) pts had died. The estimated overall survival was 28.6 months for pts with <5 CTC and 19.1 months for those with ≥5 CTC (log-rank P=.001). The rates of development of new metastatic sites according to baseline value of CTC, and stratified by the original sites of disease are shown in table 1. Fifty-three (22%) pts with <5 CTC and 52 (32%) with ≥5 CTC developed new metastatic sites when progression of disease was documented (P=.028). Pts presenting with baseline CTC ≥5, and bone metastases without visceral involvement had the highest rate of development of new metastatic sites. Conclusions. Our analysis indicates that the presence of a high number of CTC before starting systemic treatment can predict for a higher probability to develop new metastatic sites on progression. This finding seems to be largely limited to pts with bone involvement at baseline. Our results may suggest the need to evaluate more effective bone-directed therapies for MBC pts with ≥5 CTC in order to prevent further progression of disease. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr PD04-03.