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

TitleClinical significance of circulating tumor cells in hormone receptor-positive metastatic breast cancer patients who received letrozole with or without bevacizumab.
Publication TypeJournal Article
Year of Publication2020
AuthorsMagbanua MJesus M, Savenkov O, Asmus EJ, Ballman K, Scott JH, Park JW, Dickler M, Partridge AH, Carey LA, Winer E, Rugo HS
JournalClin Cancer Res
Date Published2020 Jun 25
ISSN1078-0432
Abstract

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.

DOI10.1158/1078-0432.CCR-20-1329
Alternate JournalClin. Cancer Res.
PubMed ID32586939
Grant ListUG1 CA233329 / CA / NCI NIH HHS / United States
U10 CA180821 / CA / NCI NIH HHS / United States
UG1 CA233373 / CA / NCI NIH HHS / United States
UG1 CA233180 / CA / NCI NIH HHS / United States
U24 CA196171 / CA / NCI NIH HHS / United States
U10 CA180820 / CA / NCI NIH HHS / United States
U10 CA180888 / CA / NCI NIH HHS / United States
Division: 
Biostatistics
Category: 
Faculty Publication