Prognostic value of circulating tumor cells identified in the peripheral blood of patients with breast cancer treated with CDK4/6 inhibitors.

e15026 Background: CDK4/6 inhibitors represent an important treatment option for early and metastatic breast cancer (BC). The detection of circulating tumor cells (CTCs) is a strong adverse prognostic factor in BC, however limited data exist on their prognostic value in patients receiving treatment with CDK4/6 inhibitors. We herein aimed to assess the prognostic value of CTCs, isolated with different assays, in patients treated with CDK4/6 inhibitors. Methods: Peripheral blood (PB) was obtained from 67 patients with BC (early stage: n = 9; metastatic stage: n = 58), prior to the start of CDK4/6 inhibitors plus endocrine treatment. CTCs were in parallel enriched using Ficoll density gradient centrifugation and the automated size-based Parsortix system (ANGLE plc). CTCs were identified via immunofluorescence staining with antibodies against cytokeratins (CKs)/CD45/dapi, followed by assessment using fluorescence microscopy. Results: CTCs (CK+/CD45- cells) were detected in 14.3% and 38.5% of patients with early and metastatic BC, respectively (mean CTC number per patient: n = 1.17 vs 3.15; p = 0.316). The enrichment of CTCs using different approaches, Ficoll and Parsortix, did not affect the overall CTC detection rate, which was 11.4% and 4.5% using the cut-off values of ≥2 CTCs and ≥5 CTCs, respectively. However, the positivity concordance rate between the two assays was only 6.8%. CTC detection was not associated with clinicopathological features or response to treatment. However, in the metastatic setting, a reduced overall survival (OS) was demonstrated among patients with detectable ≥2 CTCs and ≥5 CTCs using the Parsortix system (median OS: 15.5 versus 48.4 months; p = 0.000, and median OS: 11.2 versus 47.2 months; p = 0.000, respectively; Kaplan Meier analysis). Conclusions: CTCs are more frequently detected in patients with metastatic as compared to early stage BC. The Ficoll and Parsortix approaches provide similar CTC positivity rates, however they allow CTC detection mostly in different patients. The results also support an adverse prognostic value of CTCs identified by the Parsortix system for patients with metastatic BC treated with CDK4/6 inhibitors.