Clinical significance of circulating tumor cells in hormone receptor-positive metastatic breast cancer patients who received letrozole with or without bevacizumab.

PURPOSE: We evaluated the prognostic and predictive value of circulating tumor cells (CTCs) hormone-receptor positive (HR+) metastatic breast cancer (MBC) patients randomized to letrozole (Let) alone or letrozole plus bevacizumab (Let+Bev) in the first-line setting (CALGB 40503).

EXPERIMENTAL DESIGN: Blood samples were collected at pretreatment and three additional time points during therapy. The presence of ≥5 CTCs per 7.5 mLs of blood was considered CTC-positive. Association of CTCs with progression-free survival (PFS) and overall survival (OS) was assessed using Cox regression models.

RESULTS: Of 343 patients treated, 294 had CTC data and were included in this analysis. Median follow-up was 39 months. In multivariable analysis, CTC-positive patients at baseline (31%) had significantly reduced PFS (HR=1.49; 95%CI: 1.12-1.97) and OS (HR=2.08; 95%CI: 1.49-2.93) compared to CTC-negative. Failure to clear CTCs during treatment was associated with significantly increased risk of progression (HR=2.2; 95%CI: 1.58-3.07) and death (HR=3.4; 95% CI: 2.36-4.88). CTC-positive patients who received only Let had the worse PFS (HR=2.3; 95% CI: 1.54-3.47) and OS (HR=2.6; 95% CI: 1.59-4.40). Median PFS in CTC-positive patients was significantly longer (18.0 versus 7.0 months) in Let+Bev versus Let arm (p=0.0009). Restricted mean survival time analysis further revealed that addition of Bev was associated with PFS benefit in both CTC-positive and CTC-negative patients, but OS benefit was only observed in CTC-positive patients.

CONCLUSIONS: CTCs were highly prognostic for the addition of Bev to first-line Let in patients with HR+ MBC. Further research to determine the potential predictive value of CTCs in this setting is warranted.