Prognostic value of HER2-positive circulating tumor cells in patients with metastatic breast cancer

Naoki Hayashi; Seigo Nakamura; Yasuharu Tokuda; Yuji Shimoda; Hiroshi Yagata; Atsushi Yoshida; Hidekazu Ota; Gabriel N. Hortobagyi; Massimo Cristofanilli; Naoto T. Ueno

doi:10.1007/s10147-011-0260-0

Prognostic value of HER2-positive circulating tumor cells in patients with metastatic breast cancer

Naoki Hayashi, Seigo Nakamura, Yasuharu Tokuda, Yuji Shimoda, Hiroshi Yagata, Atsushi Yoshida, Hidekazu Ota, Gabriel N. Hortobagyi, Massimo Cristofanilli, Naoto T. Ueno^*

^*Corresponding author for this work

Medicine, Hematology Oncology Division

Research output: Contribution to journal › Article › peer-review

77 Scopus citations

Abstract

Backgrounds The presence of ≥5 circulating tumor cells (CTCs) in 7.5 ml blood is a poor prognostic marker in metastatic breast cancer (MBC). However, the role of human epidermal growth factor receptor 2 (HER2) status in CTCs is not known. Methods We prospectively assessed the prognostic value of this parameter for patients with MBC who started a new line of systemic therapy. The CTC count (≥5 or <5) and the HER2 status in CTCs at the initiation of the therapy and 3-4 weeks later (first follow-up) were determined. Results The median follow-up time of the 52 enrolled patients was 655.0 days (18-1,275 days). HER2-positive CTCs were present in 14 of the 52 patients (26.9%) during the study period. Eight of 33 patients (24.2%) with HER2-negative primary tumors had HER2-positive CTCs during the study period. At first follow-up, patients with HER2-positive CTCs had significantly shorter progression-free (n = 6; P = 0.001) and overall (P = 0.013) survival than did patients without HER2-positive CTCs (n = 43) in log-rank analysis. In multivariate analysis, HER2-positive CTCs at first follow-up (P = 0.029) and the number of therapies patients received before this study (P = 0.006) were independent prognostic factors in terms of progression-free survival. The number of therapies (P = 0.001) and a count of ≥5 CTCs (P = 0.043) at baseline were independent prognostic factors in terms of overall survival. Conclusions We showed that HER2 status in CTCs may be a prognostic factor for MBC. Well-powered prospective studies are necessary to determine the potential role of HER2-targeted therapies for patients with HER2-positive CTCs and HER2-negative primary tumors.

Original language	English (US)
Pages (from-to)	96-104
Number of pages	9
Journal	International Journal of Clinical Oncology
Volume	17
Issue number	2
DOIs	https://doi.org/10.1007/s10147-011-0260-0
State	Published - Apr 2012

Funding

The authors thank Sachiko Ohde for statistical assistance; Bibari Nakamura, Keiko Shimizu, and all the staff from the Department of Breast Surgical Oncology, St. Luke’s International Hospital, for help in collecting clinical data; Masayuki Shimada, Takeshi Watanabe, and Yuki Matsuo from SRL Inc. for tissue analysis; and Sunita Patterson, Department of Scientific Publications, MD Anderson Cancer Center, for editorial review. This research is supported in part by the National Institutes of Health through MD Anderson’s Cancer Center Support Grant, CA016672.

Keywords

Breast neoplasm
Circulating tumor cell
HER2
Metastasis

ASJC Scopus subject areas

Hematology
Oncology
Surgery

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1007/s10147-011-0260-0

Cite this

@article{3b028061f6a047d39b0547c4cdc4dd6e,

title = "Prognostic value of HER2-positive circulating tumor cells in patients with metastatic breast cancer",

abstract = "Backgrounds The presence of ≥5 circulating tumor cells (CTCs) in 7.5 ml blood is a poor prognostic marker in metastatic breast cancer (MBC). However, the role of human epidermal growth factor receptor 2 (HER2) status in CTCs is not known. Methods We prospectively assessed the prognostic value of this parameter for patients with MBC who started a new line of systemic therapy. The CTC count (≥5 or <5) and the HER2 status in CTCs at the initiation of the therapy and 3-4 weeks later (first follow-up) were determined. Results The median follow-up time of the 52 enrolled patients was 655.0 days (18-1,275 days). HER2-positive CTCs were present in 14 of the 52 patients (26.9%) during the study period. Eight of 33 patients (24.2%) with HER2-negative primary tumors had HER2-positive CTCs during the study period. At first follow-up, patients with HER2-positive CTCs had significantly shorter progression-free (n = 6; P = 0.001) and overall (P = 0.013) survival than did patients without HER2-positive CTCs (n = 43) in log-rank analysis. In multivariate analysis, HER2-positive CTCs at first follow-up (P = 0.029) and the number of therapies patients received before this study (P = 0.006) were independent prognostic factors in terms of progression-free survival. The number of therapies (P = 0.001) and a count of ≥5 CTCs (P = 0.043) at baseline were independent prognostic factors in terms of overall survival. Conclusions We showed that HER2 status in CTCs may be a prognostic factor for MBC. Well-powered prospective studies are necessary to determine the potential role of HER2-targeted therapies for patients with HER2-positive CTCs and HER2-negative primary tumors.",

keywords = "Breast neoplasm, Circulating tumor cell, HER2, Metastasis",

author = "Naoki Hayashi and Seigo Nakamura and Yasuharu Tokuda and Yuji Shimoda and Hiroshi Yagata and Atsushi Yoshida and Hidekazu Ota and Hortobagyi, {Gabriel N.} and Massimo Cristofanilli and Ueno, {Naoto T.}",

note = "Funding Information: The authors thank Sachiko Ohde for statistical assistance; Bibari Nakamura, Keiko Shimizu, and all the staff from the Department of Breast Surgical Oncology, St. Luke{\textquoteright}s International Hospital, for help in collecting clinical data; Masayuki Shimada, Takeshi Watanabe, and Yuki Matsuo from SRL Inc. for tissue analysis; and Sunita Patterson, Department of Scientific Publications, MD Anderson Cancer Center, for editorial review. This research is supported in part by the National Institutes of Health through MD Anderson{\textquoteright}s Cancer Center Support Grant, CA016672. ",

year = "2012",

month = apr,

doi = "10.1007/s10147-011-0260-0",

language = "English (US)",

volume = "17",

pages = "96--104",

journal = "International Journal of Clinical Oncology",

issn = "1341-9625",

publisher = "Springer Japan",

number = "2",

}

TY - JOUR

T1 - Prognostic value of HER2-positive circulating tumor cells in patients with metastatic breast cancer

AU - Hayashi, Naoki

AU - Nakamura, Seigo

AU - Tokuda, Yasuharu

AU - Shimoda, Yuji

AU - Yagata, Hiroshi

AU - Yoshida, Atsushi

AU - Ota, Hidekazu

AU - Hortobagyi, Gabriel N.

AU - Cristofanilli, Massimo

AU - Ueno, Naoto T.

N1 - Funding Information: The authors thank Sachiko Ohde for statistical assistance; Bibari Nakamura, Keiko Shimizu, and all the staff from the Department of Breast Surgical Oncology, St. Luke’s International Hospital, for help in collecting clinical data; Masayuki Shimada, Takeshi Watanabe, and Yuki Matsuo from SRL Inc. for tissue analysis; and Sunita Patterson, Department of Scientific Publications, MD Anderson Cancer Center, for editorial review. This research is supported in part by the National Institutes of Health through MD Anderson’s Cancer Center Support Grant, CA016672.

PY - 2012/4

Y1 - 2012/4

N2 - Backgrounds The presence of ≥5 circulating tumor cells (CTCs) in 7.5 ml blood is a poor prognostic marker in metastatic breast cancer (MBC). However, the role of human epidermal growth factor receptor 2 (HER2) status in CTCs is not known. Methods We prospectively assessed the prognostic value of this parameter for patients with MBC who started a new line of systemic therapy. The CTC count (≥5 or <5) and the HER2 status in CTCs at the initiation of the therapy and 3-4 weeks later (first follow-up) were determined. Results The median follow-up time of the 52 enrolled patients was 655.0 days (18-1,275 days). HER2-positive CTCs were present in 14 of the 52 patients (26.9%) during the study period. Eight of 33 patients (24.2%) with HER2-negative primary tumors had HER2-positive CTCs during the study period. At first follow-up, patients with HER2-positive CTCs had significantly shorter progression-free (n = 6; P = 0.001) and overall (P = 0.013) survival than did patients without HER2-positive CTCs (n = 43) in log-rank analysis. In multivariate analysis, HER2-positive CTCs at first follow-up (P = 0.029) and the number of therapies patients received before this study (P = 0.006) were independent prognostic factors in terms of progression-free survival. The number of therapies (P = 0.001) and a count of ≥5 CTCs (P = 0.043) at baseline were independent prognostic factors in terms of overall survival. Conclusions We showed that HER2 status in CTCs may be a prognostic factor for MBC. Well-powered prospective studies are necessary to determine the potential role of HER2-targeted therapies for patients with HER2-positive CTCs and HER2-negative primary tumors.

AB - Backgrounds The presence of ≥5 circulating tumor cells (CTCs) in 7.5 ml blood is a poor prognostic marker in metastatic breast cancer (MBC). However, the role of human epidermal growth factor receptor 2 (HER2) status in CTCs is not known. Methods We prospectively assessed the prognostic value of this parameter for patients with MBC who started a new line of systemic therapy. The CTC count (≥5 or <5) and the HER2 status in CTCs at the initiation of the therapy and 3-4 weeks later (first follow-up) were determined. Results The median follow-up time of the 52 enrolled patients was 655.0 days (18-1,275 days). HER2-positive CTCs were present in 14 of the 52 patients (26.9%) during the study period. Eight of 33 patients (24.2%) with HER2-negative primary tumors had HER2-positive CTCs during the study period. At first follow-up, patients with HER2-positive CTCs had significantly shorter progression-free (n = 6; P = 0.001) and overall (P = 0.013) survival than did patients without HER2-positive CTCs (n = 43) in log-rank analysis. In multivariate analysis, HER2-positive CTCs at first follow-up (P = 0.029) and the number of therapies patients received before this study (P = 0.006) were independent prognostic factors in terms of progression-free survival. The number of therapies (P = 0.001) and a count of ≥5 CTCs (P = 0.043) at baseline were independent prognostic factors in terms of overall survival. Conclusions We showed that HER2 status in CTCs may be a prognostic factor for MBC. Well-powered prospective studies are necessary to determine the potential role of HER2-targeted therapies for patients with HER2-positive CTCs and HER2-negative primary tumors.

KW - Breast neoplasm

KW - Circulating tumor cell

KW - HER2

KW - Metastasis

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ER -

Prognostic value of HER2-positive circulating tumor cells in patients with metastatic breast cancer

Abstract

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UN SDGs

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