TY - JOUR
T1 - Prospective assessment of the prognostic value of circulating tumor cells and their clusters in patients with advanced-stage breast cancer
AU - Mu, Zhaomei
AU - Wang, Chun
AU - Ye, Zhong
AU - Austin, Laura
AU - Civan, Jesse
AU - Hyslop, Terry
AU - Palazzo, Juan P.
AU - Jaslow, Rebecca
AU - Li, Bingshan
AU - Myers, Ronald E.
AU - Jiang, Juntao
AU - Xing, Jinliang
AU - Yang, Hushan
AU - Cristofanilli, Massimo
N1 - Funding Information:
The work reported in this study received supports from Thomas Jefferson University, The Inflammatory Breast Cancer Network Foundation, The Jamie Lieberman Memorial Endowment Fund, and American Cancer Society Research Scholar Grant 123741-RSG-13-003-01-CCE.
Publisher Copyright:
© 2015, Springer Science+Business Media New York.
PY - 2015/12/1
Y1 - 2015/12/1
N2 - The enumeration of circulating tumor cells (CTCs) provides important prognostic values in patients with metastatic breast cancer. Recent studies indicate that individual CTCs form clusters and these CTC-clusters play an important role in tumor metastasis. We aimed to assess whether quantification of CTC-clusters provides additional prognostic value over quantification of individual CTCs alone. In 115 prospectively enrolled advanced-stage (III and IV) breast cancer patients, CTCs and CTC-clusters were counted in 7.5 ml whole blood using the CellSearch® system at baseline before first-line therapy. The individual and joint effects of CTC and CTC cluster counts on patients’ progression-free survival (PFS) were analyzed using Cox proportional hazards modeling. Of the 115 patients, 36 (31.3 %) had elevated baseline CTCs (≥5 CTCs/7.5 ml) and 20 (17.4 %) had CTC-clusters (≥2 CTCs/7.5 ml). Patients with elevated CTCs and CTC-clusters both had worse PFS with a hazard ratio (HR) of 2.76 [95 % confidence interval (CI) 1.57–4.86, Plog-rank = 0.0005] and 2.83 (1.48–5.39, Plog-rank = 0.001), respectively. In joint analysis, compared with patients with <5 CTCs and without CTC-clusters, patients with elevated CTCs but without clusters, and patients with elevated CTCs and with clusters, had an increasing trend of progression risk, with an HR of 2.21 (1.02–4.78) and 3.32 (1.68–6.55), respectively (Plog-rank = 0.0006, Ptrend = 0.0002). The additional prognostic value of CTC-clusters appeared to be more pronounced in patients with inflammatory breast cancer (IBC), the most aggressive form of breast cancer with the poorest survival. Baseline counts of both individual CTCs and CTC-clusters were associated with PFS in advanced-stage breast cancer patients. CTC-clusters might provide additional prognostic value compared with CTC enumeration alone, in patients with elevated CTCs.
AB - The enumeration of circulating tumor cells (CTCs) provides important prognostic values in patients with metastatic breast cancer. Recent studies indicate that individual CTCs form clusters and these CTC-clusters play an important role in tumor metastasis. We aimed to assess whether quantification of CTC-clusters provides additional prognostic value over quantification of individual CTCs alone. In 115 prospectively enrolled advanced-stage (III and IV) breast cancer patients, CTCs and CTC-clusters were counted in 7.5 ml whole blood using the CellSearch® system at baseline before first-line therapy. The individual and joint effects of CTC and CTC cluster counts on patients’ progression-free survival (PFS) were analyzed using Cox proportional hazards modeling. Of the 115 patients, 36 (31.3 %) had elevated baseline CTCs (≥5 CTCs/7.5 ml) and 20 (17.4 %) had CTC-clusters (≥2 CTCs/7.5 ml). Patients with elevated CTCs and CTC-clusters both had worse PFS with a hazard ratio (HR) of 2.76 [95 % confidence interval (CI) 1.57–4.86, Plog-rank = 0.0005] and 2.83 (1.48–5.39, Plog-rank = 0.001), respectively. In joint analysis, compared with patients with <5 CTCs and without CTC-clusters, patients with elevated CTCs but without clusters, and patients with elevated CTCs and with clusters, had an increasing trend of progression risk, with an HR of 2.21 (1.02–4.78) and 3.32 (1.68–6.55), respectively (Plog-rank = 0.0006, Ptrend = 0.0002). The additional prognostic value of CTC-clusters appeared to be more pronounced in patients with inflammatory breast cancer (IBC), the most aggressive form of breast cancer with the poorest survival. Baseline counts of both individual CTCs and CTC-clusters were associated with PFS in advanced-stage breast cancer patients. CTC-clusters might provide additional prognostic value compared with CTC enumeration alone, in patients with elevated CTCs.
KW - Circulating tumor cell clusters (CTC-clusters)
KW - Circulating tumor cells (CTCs)
KW - Inflammatory breast cancer (IBC)
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U2 - 10.1007/s10549-015-3636-4
DO - 10.1007/s10549-015-3636-4
M3 - Article
C2 - 26573830
AN - SCOPUS:84948380709
VL - 154
SP - 563
EP - 571
JO - Breast Cancer Research and Treatment
JF - Breast Cancer Research and Treatment
SN - 0167-6806
IS - 3
ER -