Impact of apoptotic circulating tumor cells (aCTC) in metastatic breast cancer

While intact circulating tumor cells (iCTC) have independent negative prognostic impact on patients with metastatic breast cancer (MBC), the prognostic relevance of apoptotic CTC (aCTC) has not been validated in larger patient cohorts. This study assessed aCTC and iCTC statuses at baseline (CTC_BL) and CTC kinetics (CTC_KIN) as changes from CTC_BL to one completed treatment cycle for their utility in predicting response, progression-free survival (PFS), and overall survival (OS) in MBC.

Status of iCTC and aCTC was prospectively assessed in 442 patients using the CellSearch™ system. Different cutoffs were analyzed both for iCTC and aCTC (≥5, ≥10, ≥25 and ≥50 CTC/7.5 ml). CTC_KIN were characterized by ≥25 % changes in CTC counts.

Numbers of iCTC and aCTC at baseline correlated strongly (r = 0.7). For iCTC_BL positive patients, additional detection of aCTC_BL had a significant prognostic impact on OS (aCTC_BL positive 10.3 vs. aCTC_BL negative 16.4 months, p = 0.012). Worst prognosis for OS was observed in patients with ≥50 iCTC/7.5 ml and simultaneously detected aCTC. Determination of aCTC_KIN showed stronger discriminating power than iCTC_KIN, with higher PFS and OS for the group with decreasing CTCs (PFS 7.7 vs. 6.1; OS 22.2 vs. 16.4).

Intact and aCTC are predictive of outcome in MBC. Apoptotic CTC counts ≥ 5/7.5 ml in conjunction with iCTC at baseline have an independent unfavorable prognostic impact on OS. Decreasing aCTC_KIN at ≥ 5/7.5 ml in serial enumeration is associated with favorable outcome. Therefore, separate enumeration of iCTC and aCTC is useful in tailoring systemic treatment.