Serial enumeration of circulating tumor cells predicts treatment response and prognosis in metastatic breast cancer: a prospective study in 393 patients

BACKGROUND: To prospectively assess circulating tumor cell (CTC) status at baseline (CTC(BL)) and after one cycle of a new line of systemic therapy (CTC(1C)), and changes from CTC(BL) to CTC(1C) (CTC kinetics, CTC(KIN)) for their utility in predicting response, progression-free (PFS) and overall survival (OS) in metastatic breast cancer (MBC). METHODS: CTC(BL) and CTC(1C) status was determined as negative (-) or positive (+) for < 5 or ≥ 5 CTCs/7.5 ml blood using CellSearch™ (Veridex). CTC(KIN) was categorized as favorable (CTC(1C)-) or unfavorable (CTC(1C)+). Tumor response was to be assessed every 2–3 months using the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Statistical analysis focused on the relation between CTC status and CTC(KIN), and response, PFS, and OS. RESULTS: 133/393 (34%) patients enrolled were CTC(BL)+. CTC(1C) status after one cycle and radiological tumor response were assessed after median (range) periods of 1.2 (0.5–3.2) and 2.9 (0.5–4.8) months, respectively. 57/201 (28%) were CTC(1C)+. Median [95% confidence interval] PFS and OS (months) were significantly reduced in CTC(BL)+ vs. CTC(BL)- patients (PFS 4.7 [3.7–6.1] vs. 7.8 [6.4–9.2]; OS 10.4 [7.9–15.0] vs. 27.2 [22.3–29.9]), and for CTC(1C)+ vs. CTC(1C)- patients (PFS 4.3 [3.6–6.0] vs. 8.5 [6.6–10.4]; OS 7.7 [6.4–13.9] vs. 30.6 [22.6–not available]). Unfavorable CTC(KIN) was significantly associated with progressive disease. Multivariate Cox regression analysis revealed prognostic factors for shorter PFS (CTC(BL)+, persistent CTCs after one cycle, ≥ 3rd-line therapy, and triple-negative receptor status) and shorter OS (CTC(BL)+, persistent CTCs after one cycle, bone-and-visceral/local metastases, ≥ 3rd-line therapy, and triple-negative receptor status). CONCLUSIONS: CTC(BL), CTC(1C), and CTC(KIN) are predictive of outcome in MBC. Serial CTC enumeration is useful in tailoring systemic treatment of MBC. TRIAL REGISTRATION: Not applicable.