Characterization of Metastatic Breast Cancer Patients with Non-Detectable Circulating Tumor Cells.

Abstract Background: Circulating tumor cells (CTC) are independent predictor of progression free and overall survival in metastatic breast cancer patients, with superior prognosis for patients with CTC <5 per 7.5mL of peripheral blood. However, 30-50% of patients have non-detectable CTC. The aim of this study was to assess the prognostic factors in MBC patients with non-detectable CTC.Methods: This retrospective study included 271 MBC patients evaluated between January 2004 and December 2007. Median age of patients was 56 years (range: 23-82 years). CTCs were enumerated before patients started a new line of treatment using the CellSearchTM. Overall survival (OS) was calculated from the date of CTC measurement, estimated by the Kaplan-Meier product limit method, and compared between groups with the log-rank test.Results: Median CTC count was 2 (range: 0-1780) per 7.5 mL. CTCs were not detected in 99 (36.5%) patients, while 112 (41.3%) patients had CTC ≥ 5. Median OS for patients with 0 CTC; 1-4 CTC and ≥ 5 CTC was 29.3; 26.4; and 19.4 months (p = 0.04), respectively. Patients with brain metastasis have the highest probability of non-detectable CTC (71.4% vs. 33.6%; p = 0.001), while patients with bone metastasis are more likely to have CTC ≥ 1 (48.2% vs. 31.8%; p = 0.01). There was no association between other tumor characteristics (ER, PR, HER2, number and localization of tumor metastasis) and non-detectable CTC status. Patients with CTC = 0 have non-significantly better OS compared to patients with CTC ≥ 1 (29.3 vs. 23.3 months; p = 0.09) and have superior survival in all but one analyzed subgroups; only inflammatory breast cancer (IBC) patients with CTC = 0 have inferior OS compared with patients with CTC ≥ 1 (26 vs. 37 months; p = 0.67). In a subgroup of patients with non-detectable CTC, triple negative MBC has the poorest survival (median OS = 18.8 months), while hormone receptor positive MBC, without visceral metastases and non-inflammatory breast cancer has the best survival (median OS = 36.9 months). In multivariate analysis, hormone receptor status and line of therapy were only independent prognostic factors for OS in patients with non-detectable CTC (Table 1).Conclusion: Patients with non-detectable CTC before start of new line of therapy comprise a heterogeneous group of patients with substantially different prognosis. Triple negative and IBC patients represent poor prognosis subgroups. These data suggest heterogeneity of microscopic disease in advanced cancer and indicate the need to investigate combining additional detection technologies. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 3006.