Circulating tumor cells (CTC) and circulating endothelial cells (CEC) in patients (pts) receiving adjuvant bevacizumab (B) plus dose-dense (dd) doxorubicin/cyclophosphamide (AC) followed by nab-paclitaxel (nab-P) for early-stage breast cancer (ESBC).

Abstract

579 Background: Women with high risk ESBC remain at substantial risk of relapse despite adjuvant chemotherapy (AT). Current testing does not completely stratify individual risk of relapse, or assess response to AT. CTC predict outcome in metastatic BC, and CEC have been associated with response to antiangiogenic therapy. We evaluated CTC and CEC during AT plus the angiogenesis inhibitor B. Methods: In a phase II trial at 2 centers,80 pts with HER2- ESBC were treated with q2 week AC (60/600 mg/m2) × 4 followed by q2wk nab-P (260 mg/m2) × 4 with pegfilgrastin on day 2 plus B for one year (10 mg/kg IV q2wk × 8 with chemotherapy then 15 mg/kg q3wk); radiation and endocrine therapy per standard of care. The primary endpoint was cardiac safety. Blood for CTC and CEC was analyzed at baseline, week 2, 8, 16 and q3 mo for 12 mo. CTC were measured using a 2 step analysis. Cells were enriched using anti-EpCAM coated immunomagnetic beads; CTC were analyzed by multiparametric flow cytometry (FC) and defined as EpCAM+, CD45-, with thioflavin as a nucleic acid marker. CEC were evaluated by FC and defined as CD45-, CD31+ or CD146+ and CD34+ and with low side scatter. Results: 80 pts were enrolled; 16 patients withdrew early due to toxicity. Median FU is 33 mo (range [R] 0.5- 40 mo). 10 pts have relapsed; median TTP is 19.5 mo (R 0.5- 27 mo). Cardiac toxicity data has been presented (Dickler et al, ASCO 2007). Baseline median CTC was 0.28 (R 0 - 96). Baseline median CEC was 11.65 for CD31+ and 2.21 for CD146+. Baseline CTC predicted recurrence; p=0.002 for CTC as a continuous variable and p = 0.03 using a cutpoint of 1 by Wilcoxon log-rank test. CEC at baseline did not predict progression. CTC did not change over time (p = 0.16); CEC decreased - 0.5/week for CD31+ (p < 0.001), and -0.04/wk for CD146+ (p = 0.001). Conclusions: CTC at baseline predicted recurrence, and CEC continuously decreased during dd AC/nab-P combined with B. CTC have the potential to stratify pts at increased risk of recurrence at baseline, and reduction in CEC may be a marker of B effect. Further FU is required to evaluate the prognostic value of serial CTC and CEC. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech Abraxis BioScience, Genentech Abraxis BioScience, Genentech