Prognostic significance of circulating tumor cell (CTC) levels at various times during first- and second-line chemotherapy for metastatic breast cancer (MBC).

Abstract

e21077 Background: CTCs have prognostic capability in the treatment of MBC based on a dichotomous level of ≥5/7.5 ml blood (Hi) vs. <5/7.5 ml blood (Lo) at baseline and first follow-up. The value of CTCs beyond baseline is not well established, and the implication of values that are reduced but remain high has not been explored. Methods: Chart review of patients (pts) on 1st or 2nd line treatment of MBC, with CTC determinations between 2/2008 and 9/2011, were retrospectively identified at a large community oncology practice. Pts with ≥2 CTCs or 1 CTC ≥5 were eligible. Demographics, treatment regimens and progression-free survival (PFS) were assessed. The Veridex Cell Search system was utilized for all CTC determinations. Qualifying baseline CTCs were those drawn -14 days to +30 days from start of treatment. Results: 221 eligible pts were identified, 71 with baseline CTCs in 1st line, and 84 in 2nd line. Median age was 59.5 (range 26-90), 40.7% were African-American, 17.6% HER2+, and 63%/49% ER/PR+. The median time to baseline CTC was 5 days in the 1st line and 1 day in the 2nd line. 1st line PFS was 8.0 vs. 5.8 mo among baseline Hi vs. Lo groups (p = 0.085). 2nd line PFS was 3.7 vs. 4.0 mo for Hi and Lo groups, respectively, (ns). Follow-up CTCs were obtained at clinical convenience. A 90 day landmark was used for analysis of PFS by four baseline/follow-up CTC pattern groups. 1st line PFS showed medians ranging from 6.0 mo (Hi/Hi) to 10.2 mo (Lo/Lo). In 1st line pts with Hi baseline CTCs (n=24), median PFS was 6.0 vs. 7.0 mo for Hi vs. Lo at follow-up (p = .64). Grouping pts with Hi baseline CTCs by reductions in absolute CTC count at follow-up (<33% vs. ≥33%) showed median PFS 3.5 mo for <33% reduction, 8.8 mo for ≥33% reduction (p = .0179). Sensitivity analyses with other cutoffs in reduction from 20-80% showed similar results. Conclusions: In the community setting, baseline and subsequent CTCs obtained at various times after baseline yield clinically useful prognostic information. Pts with positive baseline CTC levels experiencing a reduction of ≥33% exhibit significantly longer PFS, indicating that a simple high/low approach to the test can be modified to yield more prognostic value.