Zhaomei Mu1, Chun Wang2, Zhong Ye2, Giovanna Rossi3,4, Carl Sun2, Ling Li2, Zhu Zhu2, Hushan Yang2, Massimo Cristofanilli5. 1. Department of Medicine-Hematology and Oncology, Robert H Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA. zmu22001@yahoo.com. 2. Department of Medical Oncology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, 19107, USA. 3. Department of Medicine-Hematology and Oncology, Robert H Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA. 4. Division of Thoracic Oncology, European Institute of Oncology, Milan, Italy. 5. Department of Medicine-Hematology and Oncology, Robert H Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA. massimo.cristofanilli@nm.org.
Abstract
PURPOSE: Circulating cancer associated macrophage-like cells (CAMLs) have been detected in the peripheral blood of patients with solid tumors including breast cancer. However, the prognostic relevance of CAMLs in metastatic breast cancer (MBC) has not been evaluated. In the present study, we aimed to measure CAMLs and circulating tumor cells (CTCs) at baseline and examine their prognostic value in patients with MBC. METHODS: Peripheral blood samples from 127 MBC patients were collected at baseline before starting a new treatment. The detection and enumeration of CAMLs and CTCs in 7.5 ml whole blood were performed using the CellSearch™ system. The associations of CAMLs and CTCs with the progression-free survival (PFS) and overall survival (OS) in the patients were evaluated using Kaplan-Meier curves and Cox proportional hazards modeling. RESULTS: Among 127 MBC patients, 21 (16.5%) were detected with CAMLs and 38 (29.9%) had elevated CTCs (≥5 CTCs/7.5 ml). Patients with CAMLs at baseline had worse PFS and OS with an adjusted hazard ratio (HR) of 1.75 (95% CI 1.03-2.98, P = 0.0374) and 3.75 (95% CI 1.52-9.26, P = 0.0042), compared to patients without CAMLs. Compared with patients with <5 CTCs and without CAMLs, patients with <5 CTCs and with CAMLs, with ≥5 CTCs but without CAMLs, or with ≥5 CTCs and with CAMLs, had an increasing trend of risk of disease progression (HR = 0.84, 3.42 and 4.04 respectively, P for trend <0.0001) and death (HR = 2.66, 6.14, and 9.13, respectively, P for trend <0.0001). CONCLUSION: Baseline enumeration of individual CAMLs is an independent indicator for MBC patients' survival. Evaluation of CAMLs in peripheral blood might provide a potential biomarker with additional prognostic values over CTC enumeration alone in MBC patients.
PURPOSE: Circulating cancer associated macrophage-like cells (CAMLs) have been detected in the peripheral blood of patients with solid tumors including breast cancer. However, the prognostic relevance of CAMLs in metastatic breast cancer (MBC) has not been evaluated. In the present study, we aimed to measure CAMLs and circulating tumor cells (CTCs) at baseline and examine their prognostic value in patients with MBC. METHODS: Peripheral blood samples from 127 MBCpatients were collected at baseline before starting a new treatment. The detection and enumeration of CAMLs and CTCs in 7.5 ml whole blood were performed using the CellSearch™ system. The associations of CAMLs and CTCs with the progression-free survival (PFS) and overall survival (OS) in the patients were evaluated using Kaplan-Meier curves and Cox proportional hazards modeling. RESULTS: Among 127 MBCpatients, 21 (16.5%) were detected with CAMLs and 38 (29.9%) had elevated CTCs (≥5 CTCs/7.5 ml). Patients with CAMLs at baseline had worse PFS and OS with an adjusted hazard ratio (HR) of 1.75 (95% CI 1.03-2.98, P = 0.0374) and 3.75 (95% CI 1.52-9.26, P = 0.0042), compared to patients without CAMLs. Compared with patients with <5 CTCs and without CAMLs, patients with <5 CTCs and with CAMLs, with ≥5 CTCs but without CAMLs, or with ≥5 CTCs and with CAMLs, had an increasing trend of risk of disease progression (HR = 0.84, 3.42 and 4.04 respectively, P for trend <0.0001) and death (HR = 2.66, 6.14, and 9.13, respectively, P for trend <0.0001). CONCLUSION: Baseline enumeration of individual CAMLs is an independent indicator for MBCpatients' survival. Evaluation of CAMLs in peripheral blood might provide a potential biomarker with additional prognostic values over CTC enumeration alone in MBCpatients.
Entities:
Keywords:
Circulating cancer associated macrophage-like cells (CAMLs); Circulating tumor cells (CTCs); Metastatic breast cancer (MBC); Overall survival (OS); Prognosis; Progression-free survival (PFS)
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