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

Abstract

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.