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Longitudinal enumeration and cluster evaluation of circulating tumor cells improve prognostication for patients with newly diagnosed metastatic breast cancer in a prospective observational trial

Larsson, Anna Maria LU ; Jansson, Sara LU ; Bendahl, Pär Ola LU ; Levin Tykjaer Jörgensen, Charlotte LU ; Loman, Niklas LU ; Graffman, Cecilia LU ; Lundgren, Lotta LU ; Aaltonen, Kristina LU and Rydén, Lisa LU (2018) In Breast Cancer Research 20(1). p.1-14
Abstract

Background: Circulating tumor cells (CTCs) carry independent prognostic information in patients with metastatic breast cancer (MBC) on different lines of therapy. Moreover, CTC clusters are suggested to add prognostic information to CTC enumeration alone but their significance is unknown in patients with newly diagnosed MBC. We aimed to evaluate whether longitudinal enumeration of circulating tumor cells (CTCs) and CTC clusters could improve prognostication and monitoring of patients with metastatic breast cancer (MBC) starting first-line therapy. Methods: This prospective study included 156 women with newly diagnosed MBC. CTCs and CTC clusters were detected using CellSearch technology at baseline (BL) and after 1, 3, and 6months of... (More)

Background: Circulating tumor cells (CTCs) carry independent prognostic information in patients with metastatic breast cancer (MBC) on different lines of therapy. Moreover, CTC clusters are suggested to add prognostic information to CTC enumeration alone but their significance is unknown in patients with newly diagnosed MBC. We aimed to evaluate whether longitudinal enumeration of circulating tumor cells (CTCs) and CTC clusters could improve prognostication and monitoring of patients with metastatic breast cancer (MBC) starting first-line therapy. Methods: This prospective study included 156 women with newly diagnosed MBC. CTCs and CTC clusters were detected using CellSearch technology at baseline (BL) and after 1, 3, and 6months of systemic therapy. The primary end point was progression-free survival (PFS) and the secondary end point overall survival (OS). Median follow-up time was 25 (7-69) months. Results: There were 79 (52%) and 30 (20%) patients with ≥5 CTCs and≥1 CTC cluster at baseline, respectively; both factors were significantly associated with impaired survival. Landmark analyses based on follow-up measurements revealed increasing prognostic hazard ratios for ≥5 CTCs and CTC clusters during treatment, predicting worse PFS and OS. Both factors added value to a prognostic model based on clinicopathological variables at all time points and ≥5 CTCs and presence of CTC clusters enhanced the model's C-index to >0.80 at 1, 3, and 6months. Importantly, changes in CTCs during treatment were significantly correlated with survival and patients with a decline from ≥5 CTCs at BL to <5 CTCs at 1month had a similar odds ratio for progression to patients with <5 CTCs at BL and 1month. Stratification of patients based on CTC count and CTC clusters into four groups (0 CTCs, 1-4 CTCs, ≥5 CTCs, and ≥1 CTC+CTC clusters) demonstrated that patients with CTC clusters had significantly worse survival compared to patients without clusters. Conclusions: Longitudinal evaluation of CTC and CTC clusters improves prognostication and monitoring in patients with MBC starting first-line systemic therapy. The prognostic value increases over time, suggesting that changes in CTC count are clinically relevant. The presence of CTC clusters adds significant prognostic value to CTC enumeration alone.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Circulating tumor cells (CTCs), Cluster, Enumeration, Metastatic breast cancer, Prognosis
in
Breast Cancer Research
volume
20
issue
1
pages
1 - 14
publisher
BioMed Central
external identifiers
  • scopus:85048258335
ISSN
1465-5411
DOI
10.1186/s13058-018-0976-0
language
English
LU publication?
yes
id
2788bd07-4055-4e5f-af50-ca2b63c47ac6
date added to LUP
2019-05-25 23:41:29
date last changed
2019-07-16 04:10:07
@article{2788bd07-4055-4e5f-af50-ca2b63c47ac6,
  abstract     = {<p>Background: Circulating tumor cells (CTCs) carry independent prognostic information in patients with metastatic breast cancer (MBC) on different lines of therapy. Moreover, CTC clusters are suggested to add prognostic information to CTC enumeration alone but their significance is unknown in patients with newly diagnosed MBC. We aimed to evaluate whether longitudinal enumeration of circulating tumor cells (CTCs) and CTC clusters could improve prognostication and monitoring of patients with metastatic breast cancer (MBC) starting first-line therapy. Methods: This prospective study included 156 women with newly diagnosed MBC. CTCs and CTC clusters were detected using CellSearch technology at baseline (BL) and after 1, 3, and 6months of systemic therapy. The primary end point was progression-free survival (PFS) and the secondary end point overall survival (OS). Median follow-up time was 25 (7-69) months. Results: There were 79 (52%) and 30 (20%) patients with ≥5 CTCs and≥1 CTC cluster at baseline, respectively; both factors were significantly associated with impaired survival. Landmark analyses based on follow-up measurements revealed increasing prognostic hazard ratios for ≥5 CTCs and CTC clusters during treatment, predicting worse PFS and OS. Both factors added value to a prognostic model based on clinicopathological variables at all time points and ≥5 CTCs and presence of CTC clusters enhanced the model's C-index to &gt;0.80 at 1, 3, and 6months. Importantly, changes in CTCs during treatment were significantly correlated with survival and patients with a decline from ≥5 CTCs at BL to &lt;5 CTCs at 1month had a similar odds ratio for progression to patients with &lt;5 CTCs at BL and 1month. Stratification of patients based on CTC count and CTC clusters into four groups (0 CTCs, 1-4 CTCs, ≥5 CTCs, and ≥1 CTC+CTC clusters) demonstrated that patients with CTC clusters had significantly worse survival compared to patients without clusters. Conclusions: Longitudinal evaluation of CTC and CTC clusters improves prognostication and monitoring in patients with MBC starting first-line systemic therapy. The prognostic value increases over time, suggesting that changes in CTC count are clinically relevant. The presence of CTC clusters adds significant prognostic value to CTC enumeration alone.</p>},
  articleno    = {48},
  author       = {Larsson, Anna Maria and Jansson, Sara and Bendahl, Pär Ola and Levin Tykjaer Jörgensen, Charlotte and Loman, Niklas and Graffman, Cecilia and Lundgren, Lotta and Aaltonen, Kristina and Rydén, Lisa},
  issn         = {1465-5411},
  keyword      = {Circulating tumor cells (CTCs),Cluster,Enumeration,Metastatic breast cancer,Prognosis},
  language     = {eng},
  month        = {06},
  number       = {1},
  pages        = {1--14},
  publisher    = {BioMed Central},
  series       = {Breast Cancer Research},
  title        = {Longitudinal enumeration and cluster evaluation of circulating tumor cells improve prognostication for patients with newly diagnosed metastatic breast cancer in a prospective observational trial},
  url          = {http://dx.doi.org/10.1186/s13058-018-0976-0},
  volume       = {20},
  year         = {2018},
}