Global evaluation of minimal residual disease in primary breast cancer patients

Abstract

1020 Background: Disseminated tumor cells (DTCs) in bone marrow (BM) are correlated with worse outcome, yet there is little data on circulating tumor cells (CTCs) in operable patients. We hypothesized that a significant number of primary breast cancer patients have minimal residual disease (MRD= CTCs and/or DTCs) that correlates with primary tumor characteristics. Methods: We prospectively evaluated MRD in stage I-III patients. Bilateral anterior iliac crest BM aspirates (10ml each side) were processed by cytospin, Ficoll gradient, and ICC for cytokeratin (CK). Cells staining for CK (with malignant morphology) were DTC positive. CTCs were assessed using 30 ml of peripheral blood in a CellSearch system (Veridex, Warren, NJ), and were defined as ≥1 nucleated cell/10 ml lacking CD 45 but expressing CK 8, 18, or 19. Tumor characteristics compared with MRD included: T size, lymph node status, LVSI, ER, PgR, Her-2, and Ki-67. Patients who received chemotherapy prior to BM/ blood collection were included. Statistical analyses were performed using chi-square tests. Results: We enrolled 124 patients; two were lost to follow-up. BM was evaluable in 93/124 (75%), and blood in 106/124 (85%). Median follow-up is 18 mos. Table 1 shows clinicopathologic characteristics. Seventy-five percent (91/122) of patients received no systemic therapy prior to BM/blood collection. CTCs and DTCs were found in 36 %( 38/106) and 23 % (21/93) of patients respectively. Seventeen percent (18/106) had ≥ 2 CTCs, and 6% (6/106) had >5 CTCs. There was no statistically significant correlation between CTCs and DTCs. No tumor characteristics correlated with DTCs, but Her-2 positivity correlated with CTCs (p=0.02, OR= 4.2). There was no difference in rates of MRD in patients who received chemotherapy versus those who had not. Conclusions: CTCs and DTCs are found in a significant number of patients with primary breast cancer. No correlation existed between presence of CTCs and DTCs. Except for Her-2 and CTCs, primary tumor characteristics did not reliably predict presence of MRD. Patient Clinicopathologic Characteristics T1 31% (39/124) T2 43% (53/124) T3 8% (10/124) T4 18% (22/124) ER 61% (75/124) PgR 51% (63/124) Her2 15% (18/124) Ki-67, high 53% (27/51) Lymph Node Status 48% (57/118) LVSI 35%( 42/119) Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Veridex