c-MET-positive circulating tumor cells and cell-free DNA as independent prognostic factors in hormone receptor-positive/HER2-negative metastatic breast cancer

Jieun Park; Eun Sol Chang; Ji Yeon Kim; Chaithanya Chelakkot; Minjung Sung; Ji Young Song; Kyungsoo Jung; Ji Hye Lee; Jun Young Choi; Na Young Kim; Hyegyeong Lee; Mi Ran Kang; Mi Jeong Kwon; Young Kee Shin; Yeon Hee Park; Yoon La Choi

doi:10.1186/s13058-024-01768-y

c-MET-positive circulating tumor cells and cell-free DNA as independent prognostic factors in hormone receptor-positive/HER2-negative metastatic breast cancer

Jieun Park, Eun Sol Chang, Ji Yeon Kim, Chaithanya Chelakkot, Minjung Sung, Ji Young Song, Kyungsoo Jung, Ji Hye Lee, Jun Young Choi, Na Young Kim, Hyegyeong Lee, Mi Ran Kang, Mi Jeong Kwon, Young Kee Shin, Yeon Hee Park, Yoon La Choi

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

8 Scopus citations

Abstract

Background: Endocrine therapy resistance in hormone receptor-positive/HER2-negative (HR+/HER2−) breast cancer (BC) is a significant clinical challenge that poses several unmet needs in the management of the disease. This study aimed to investigate the prognostic value of c-MET-positive circulating tumor cells (cMET+ CTCs), ESR1/PIK3CA mutations, and cell-free DNA (cfDNA) concentrations in patients with hormone receptor-positive (HR+) metastatic breast cancer (mBC). Methods: Ninety-seven patients with HR+ mBC were prospectively enrolled during standard treatment at Samsung Medical Center. CTCs were isolated from blood using GenoCTC^® and EpCAM or c-MET CTC isolation kits. PIK3CA and ESR1 hotspot mutations were analyzed using droplet digital PCR. CfDNA concentrations were calculated using internal control copies from the ESR1 mutation test. Immunocytochemistry was performed to compare c-MET overexpression between primary and metastatic sites. Results: The proportion of c-MET overexpression was significantly higher in metastatic sites than in primary sites (p = 0.00002). Survival analysis showed that c-MET+ CTC, cfDNA concentration, and ESR1 mutations were significantly associated with poor prognosis (p = 0.0026, 0.0021, and 0.0064, respectively) in HR+/HER2− mBC. By contrast, EpCAM-positive CTC (EpCAM+ CTC) and PIK3CA mutations were not associated with progression-free survival (PFS) in HR+/HER2− mBC. Multivariate analyses revealed that c-MET+ CTCs and cfDNA concentration were independent predictors of PFS in HR+/HER2− mBC. Conclusions: Monitoring c-MET+ CTC, rather than assessing c-MET expression in the primary BC site, could provide valuable information for predicting disease progression, as c-MET expression can change during treatment. The c-MET+ CTC count and cfDNA concentration could provide complementary information on disease progression in HR+ /HER2− mBC, highlighting the importance of integrated liquid biopsy.

Original language	English
Article number	13
Journal	Breast Cancer Research
Volume	26
Issue number	1
DOIs	https://doi.org/10.1186/s13058-024-01768-y
State	Published - 18 Jan 2024

Keywords

Cell-free DNA
Circulating tumor cells
Metastatic breast cancer
Prognostic biomarkers
c-MET

UN SDGs

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

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10.1186/s13058-024-01768-y

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Park, J., Chang, E. S., Kim, J. Y., Chelakkot, C., Sung, M., Song, J. Y., Jung, K., Lee, J. H., Choi, J. Y., Kim, N. Y., Lee, H., Kang, M. R., Kwon, M. J., Shin, Y. K., Park, Y. H., & Choi, Y. L. (2024). c-MET-positive circulating tumor cells and cell-free DNA as independent prognostic factors in hormone receptor-positive/HER2-negative metastatic breast cancer. Breast Cancer Research, 26(1), Article 13. https://doi.org/10.1186/s13058-024-01768-y

@article{3fb7b70c765a4c02939875856d17880d,

title = "c-MET-positive circulating tumor cells and cell-free DNA as independent prognostic factors in hormone receptor-positive/HER2-negative metastatic breast cancer",

abstract = "Background: Endocrine therapy resistance in hormone receptor-positive/HER2-negative (HR+/HER2−) breast cancer (BC) is a significant clinical challenge that poses several unmet needs in the management of the disease. This study aimed to investigate the prognostic value of c-MET-positive circulating tumor cells (cMET+ CTCs), ESR1/PIK3CA mutations, and cell-free DNA (cfDNA) concentrations in patients with hormone receptor-positive (HR+) metastatic breast cancer (mBC). Methods: Ninety-seven patients with HR+ mBC were prospectively enrolled during standard treatment at Samsung Medical Center. CTCs were isolated from blood using GenoCTC{\textregistered} and EpCAM or c-MET CTC isolation kits. PIK3CA and ESR1 hotspot mutations were analyzed using droplet digital PCR. CfDNA concentrations were calculated using internal control copies from the ESR1 mutation test. Immunocytochemistry was performed to compare c-MET overexpression between primary and metastatic sites. Results: The proportion of c-MET overexpression was significantly higher in metastatic sites than in primary sites (p = 0.00002). Survival analysis showed that c-MET+ CTC, cfDNA concentration, and ESR1 mutations were significantly associated with poor prognosis (p = 0.0026, 0.0021, and 0.0064, respectively) in HR+/HER2− mBC. By contrast, EpCAM-positive CTC (EpCAM+ CTC) and PIK3CA mutations were not associated with progression-free survival (PFS) in HR+/HER2− mBC. Multivariate analyses revealed that c-MET+ CTCs and cfDNA concentration were independent predictors of PFS in HR+/HER2− mBC. Conclusions: Monitoring c-MET+ CTC, rather than assessing c-MET expression in the primary BC site, could provide valuable information for predicting disease progression, as c-MET expression can change during treatment. The c-MET+ CTC count and cfDNA concentration could provide complementary information on disease progression in HR+ /HER2− mBC, highlighting the importance of integrated liquid biopsy.",

keywords = "Cell-free DNA, Circulating tumor cells, Metastatic breast cancer, Prognostic biomarkers, c-MET",

author = "Jieun Park and Chang, {Eun Sol} and Kim, {Ji Yeon} and Chaithanya Chelakkot and Minjung Sung and Song, {Ji Young} and Kyungsoo Jung and Lee, {Ji Hye} and Choi, {Jun Young} and Kim, {Na Young} and Hyegyeong Lee and Kang, {Mi Ran} and Kwon, {Mi Jeong} and Shin, {Young Kee} and Park, {Yeon Hee} and Choi, {Yoon La}",

note = "Publisher Copyright: {\textcopyright} 2024, The Author(s).",

year = "2024",

month = jan,

day = "18",

doi = "10.1186/s13058-024-01768-y",

language = "English",

volume = "26",

journal = "Breast Cancer Research",

issn = "1465-5411",

publisher = "BioMed Central Ltd.",

number = "1",

}

Park, J, Chang, ES, Kim, JY, Chelakkot, C, Sung, M, Song, JY, Jung, K, Lee, JH, Choi, JY, Kim, NY, Lee, H, Kang, MR, Kwon, MJ, Shin, YK, Park, YH & Choi, YL 2024, 'c-MET-positive circulating tumor cells and cell-free DNA as independent prognostic factors in hormone receptor-positive/HER2-negative metastatic breast cancer', Breast Cancer Research, vol. 26, no. 1, 13. https://doi.org/10.1186/s13058-024-01768-y

TY - JOUR

T1 - c-MET-positive circulating tumor cells and cell-free DNA as independent prognostic factors in hormone receptor-positive/HER2-negative metastatic breast cancer

AU - Park, Jieun

AU - Chang, Eun Sol

AU - Kim, Ji Yeon

AU - Chelakkot, Chaithanya

AU - Sung, Minjung

AU - Song, Ji Young

AU - Jung, Kyungsoo

AU - Lee, Ji Hye

AU - Choi, Jun Young

AU - Kim, Na Young

AU - Lee, Hyegyeong

AU - Kang, Mi Ran

AU - Kwon, Mi Jeong

AU - Shin, Young Kee

AU - Park, Yeon Hee

AU - Choi, Yoon La

PY - 2024/1/18

Y1 - 2024/1/18

N2 - Background: Endocrine therapy resistance in hormone receptor-positive/HER2-negative (HR+/HER2−) breast cancer (BC) is a significant clinical challenge that poses several unmet needs in the management of the disease. This study aimed to investigate the prognostic value of c-MET-positive circulating tumor cells (cMET+ CTCs), ESR1/PIK3CA mutations, and cell-free DNA (cfDNA) concentrations in patients with hormone receptor-positive (HR+) metastatic breast cancer (mBC). Methods: Ninety-seven patients with HR+ mBC were prospectively enrolled during standard treatment at Samsung Medical Center. CTCs were isolated from blood using GenoCTC® and EpCAM or c-MET CTC isolation kits. PIK3CA and ESR1 hotspot mutations were analyzed using droplet digital PCR. CfDNA concentrations were calculated using internal control copies from the ESR1 mutation test. Immunocytochemistry was performed to compare c-MET overexpression between primary and metastatic sites. Results: The proportion of c-MET overexpression was significantly higher in metastatic sites than in primary sites (p = 0.00002). Survival analysis showed that c-MET+ CTC, cfDNA concentration, and ESR1 mutations were significantly associated with poor prognosis (p = 0.0026, 0.0021, and 0.0064, respectively) in HR+/HER2− mBC. By contrast, EpCAM-positive CTC (EpCAM+ CTC) and PIK3CA mutations were not associated with progression-free survival (PFS) in HR+/HER2− mBC. Multivariate analyses revealed that c-MET+ CTCs and cfDNA concentration were independent predictors of PFS in HR+/HER2− mBC. Conclusions: Monitoring c-MET+ CTC, rather than assessing c-MET expression in the primary BC site, could provide valuable information for predicting disease progression, as c-MET expression can change during treatment. The c-MET+ CTC count and cfDNA concentration could provide complementary information on disease progression in HR+ /HER2− mBC, highlighting the importance of integrated liquid biopsy.

AB - Background: Endocrine therapy resistance in hormone receptor-positive/HER2-negative (HR+/HER2−) breast cancer (BC) is a significant clinical challenge that poses several unmet needs in the management of the disease. This study aimed to investigate the prognostic value of c-MET-positive circulating tumor cells (cMET+ CTCs), ESR1/PIK3CA mutations, and cell-free DNA (cfDNA) concentrations in patients with hormone receptor-positive (HR+) metastatic breast cancer (mBC). Methods: Ninety-seven patients with HR+ mBC were prospectively enrolled during standard treatment at Samsung Medical Center. CTCs were isolated from blood using GenoCTC® and EpCAM or c-MET CTC isolation kits. PIK3CA and ESR1 hotspot mutations were analyzed using droplet digital PCR. CfDNA concentrations were calculated using internal control copies from the ESR1 mutation test. Immunocytochemistry was performed to compare c-MET overexpression between primary and metastatic sites. Results: The proportion of c-MET overexpression was significantly higher in metastatic sites than in primary sites (p = 0.00002). Survival analysis showed that c-MET+ CTC, cfDNA concentration, and ESR1 mutations were significantly associated with poor prognosis (p = 0.0026, 0.0021, and 0.0064, respectively) in HR+/HER2− mBC. By contrast, EpCAM-positive CTC (EpCAM+ CTC) and PIK3CA mutations were not associated with progression-free survival (PFS) in HR+/HER2− mBC. Multivariate analyses revealed that c-MET+ CTCs and cfDNA concentration were independent predictors of PFS in HR+/HER2− mBC. Conclusions: Monitoring c-MET+ CTC, rather than assessing c-MET expression in the primary BC site, could provide valuable information for predicting disease progression, as c-MET expression can change during treatment. The c-MET+ CTC count and cfDNA concentration could provide complementary information on disease progression in HR+ /HER2− mBC, highlighting the importance of integrated liquid biopsy.

KW - Cell-free DNA

KW - Circulating tumor cells

KW - Metastatic breast cancer

KW - Prognostic biomarkers

KW - c-MET

UR - http://www.scopus.com/inward/record.url?scp=85182697853&partnerID=8YFLogxK

U2 - 10.1186/s13058-024-01768-y

DO - 10.1186/s13058-024-01768-y

M3 - Article

C2 - 38238761

AN - SCOPUS:85182697853

SN - 1465-5411

VL - 26

JO - Breast Cancer Research

JF - Breast Cancer Research

IS - 1

M1 - 13

ER -

c-MET-positive circulating tumor cells and cell-free DNA as independent prognostic factors in hormone receptor-positive/HER2-negative metastatic breast cancer

Abstract

Keywords

UN SDGs

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