Circulating tumor cells (CTCs) and molecular subtypes (MST) in a treatment algorithm for metastatic breast cancer (MBC).

Abstract

e21022 Background: We measured CTC s and MST of MBC [ER+, HER2- (HR+); HER2+ (H2+); or Triple Negative (TN)] in all MBC pts in our practice and used these in an algorithm to treat MBC. Methods: CTC’s were measured in 156 pts whether beginning Rx with 1st MBC (97), or under way with Rx (59). Pts had CTC s measured over 61 mo. from 11/20/06 thr. 12/31/11; 66 of the pts had died as of 12/31/11. Pts were Rx’d with an algorithm using CTC’s and MST: Pts with ≥ 5 CTC s were Rx’d with chemoRx, usually doublet ChemoRx, but accounting for pt preferences. When CTC’s improved to < 5 for a sustained 3-4 mo. period, or if initially < 5m we sought less morbid therapies: hormonal if ER+, or single agent ChemoRx +/- biologics if ER- or hormone refractory. In a detailed statistical analysis of variables affecting Disease Specific Survival (DSS) in the first 140 pts thr. 6/30/11, with median f/u of 24.0 mo., highest CTC level (max CTC) observed during f/u was used for analysis: CTC Low (max <5, n=60); CTC Moderate (max 5-99; n=55); and CTC High (max ≥ 100; n=25). Results: We reported the distribution of pts and death rates for the 3 MST and the 3 max CTC groupings earlier (Graham, ASCO 2010); the conclusions are similar with 156 pts and longer f/u. Each MST has 40% of pts with 0-4 CTC’s at all time points. Each MST has a smaller group with CTC’s ≥ 100, 16% of all pts. 33% of deaths (22 of 66) occurred in the ≥ 100 CTC pts. 88% with ≥ 100 CTC’s died; these are early deaths. Only 13 of 66 (20%) died if CTC’s < 5, and 31 of 65 (48%) ifh 5-99 CTC’s. In the first 140 pt analyzed thr. 6/30/11, the median DSS from date of highest CTC is not reached for the CTC Low (max. f/u 54 mo.), vs. 35.8 mo. in the CTC Moderate and 3.3 mo. in the CTC High. DSS was signif. longer for the CTC Low and CTC Moderate vs. the CTC High (P<0.001 for both comparisons). DSS was also signif. greater in the CTC Low vs. the CTC Moderate (P = 0.04). Cox multivariate analysis showed that the Max CTC group (HR 4.8, 95% CI 3.1 - 7.6, p < 0.001), age ≥ 55 at time of max CTC (HR 4.0, 95% CI 2.7 - 7.9, p < 0.001), and MST (HR 2.1, 95% CI 1.4 – 3.1, p < 0.001) were predictive of DSS. Conclusions: a. A treatment algorithm of CTC’s and MST in MBC finds subgroups of MBC with long, intermediate and very short DSS; b. Effective treatments are short-lived in pts with CTC max ≥ 100.