Background:
We tested the hypothesis that presence of microscopic disease in both blood and bone marrow predicts outcome in non-metastatic breast cancer (BC).

Material and Methods:
We prospectively collected data on circulating (blood, CTC) and disseminated (bone marrow, DTC) tumor cells at the time of surgery in 353 stage I-III BC patients. We evaluated patient outcomes and correlated findings of microscopic disease with standard prognostic indicators. We also assessed HER2 status using FISH between primary tumor and CTC and /or DTC in a select number of patients using a microfluidic method.

Result:
At least one CTC was identified in 25% of patients, 32% had DTCs, and 7% had both CTCs and DTCs. Median follow-up time was 50 months. Univariate analysis showed that any CTC predicted worse progression-free (PFS) (p=0.05) and overall survival (OS) (p=0.04). The presence of DTCs independently predicted OS (p=0.022), but not PFS (p=0.494). Patients with one or more CTCs as well as DTCs had only a 76% chance of PFS at two years, and an 86% chance of OS at two years compared to 95% of lymph node positive patients. The overall rate of discordance in HER2 status was 15% between primary tumor and CTCs, and 28% between primary tumor and DTCs.

Conclusion:
Microscopic disease in the blood and bone marrow predicted early recurrence and decreased OS in non-metastatic BC patients. Also, HER2 discordance between the primary tumor and CTCs or DTCs occurred in a significant number of non-metastatic BC patients.