Tumor-agnostic ctDNA levels by mFAST-SeqS in first-line HR-positive, HER2 negative metastatic breast cancer patients as a biomarker for survival

Noortje Verschoor; Vanja de Weerd; Mai N. Van; Jaco Kraan; Marcel Smid; Joan B. Heijns; Jan C. Drooger; Johanna M. Zuetenhorst; Annemieke van der Padt-Pruijsten; Agnes Jager; Stefan Sleijfer; John W.M. Martens; Saskia M. Wilting

doi:10.1038/s41523-023-00563-w

Tumor-agnostic ctDNA levels by mFAST-SeqS in first-line HR-positive, HER2 negative metastatic breast cancer patients as a biomarker for survival

Noortje Verschoor^*, Vanja de Weerd, Mai N. Van, Jaco Kraan, Marcel Smid, Joan B. Heijns, Jan C. Drooger, Johanna M. Zuetenhorst, Annemieke van der Padt-Pruijsten, Agnes Jager, Stefan Sleijfer, John W.M. Martens, Saskia M. Wilting

^*Corresponding author for this work

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Abstract

This prospective cohort study reports aneuploidy score by mFast-SeqS as a strong prognostic marker in MBC patients. mFAST-SeqS is an affordable and easily implementable method for the assessment of total ctDNA levels and, as such, provides an alternative prognostic tool. One mixed cohort (cohort A, n = 45) starting any type of treatment in any line of therapy and one larger cohort (cohort B, n = 129) consisting of patients starting aromatase inhibitors (AI) as first-line therapy were used. mFAST-SeqS was performed using plasma of blood in which CTCs (CellSearch) were enumerated. The resulting aneuploidy score was correlated with categorized CTC count and associated with outcome. The aneuploidy score was significantly correlated with CTC count, but discordance was observed in 31.6% when applying cut-offs of 5. In both cohorts, aneuploidy score was a significant prognostic marker for both PFS and OS. In the Cox regression models, the HR for aneuploidy score for PFS was 2.52 (95% CI: 1.56–4.07), and the HR for OS was 2.37 (95% CI: 1.36–4.14). Results presented here warrant further investigations into the clinical utility of this marker in MBC patients.

Original language	English
Article number	61
Journal	npj Breast Cancer
Volume	9
Issue number	1
DOIs	https://doi.org/10.1038/s41523-023-00563-w
Publication status	Published - 14 Jul 2023

Bibliographical note

Funding Information:
We express our gratitude to all women who contributed their specimens to the Liquid Biobank and Caremore-AI trials. Furthermore, we would like to thank all our collaborators that included women in these trials. This trial was funded by EU-FP7, Project number 601760-2, and by the Dutch Cancer Society (KWF), grant number 12481. The current study was presented as a poster presentation (P2-03-14) at the San Antonio Breast Cancer Symposium, December 6–10, 2022, in San Antonio, Texas.

Publisher Copyright:
© 2023, The Author(s).

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Tumor-agnostic ctDNA levels by mFAST-SeqS in first-line HR-positive, HER2 negative metastatic breast cancer patients as a biomarker for survivalFinal published version, 739 KBLicence: CC BY

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Verschoor, N., de Weerd, V., Van, M. N., Kraan, J., Smid, M., Heijns, J. B., Drooger, J. C., Zuetenhorst, J. M., van der Padt-Pruijsten, A., Jager, A., Sleijfer, S., Martens, J. W. M., & Wilting, S. M. (2023). Tumor-agnostic ctDNA levels by mFAST-SeqS in first-line HR-positive, HER2 negative metastatic breast cancer patients as a biomarker for survival. npj Breast Cancer, 9(1), Article 61. https://doi.org/10.1038/s41523-023-00563-w

@article{32cec85d77494fa69238dcd95f75d4ec,

title = "Tumor-agnostic ctDNA levels by mFAST-SeqS in first-line HR-positive, HER2 negative metastatic breast cancer patients as a biomarker for survival",

abstract = "This prospective cohort study reports aneuploidy score by mFast-SeqS as a strong prognostic marker in MBC patients. mFAST-SeqS is an affordable and easily implementable method for the assessment of total ctDNA levels and, as such, provides an alternative prognostic tool. One mixed cohort (cohort A, n = 45) starting any type of treatment in any line of therapy and one larger cohort (cohort B, n = 129) consisting of patients starting aromatase inhibitors (AI) as first-line therapy were used. mFAST-SeqS was performed using plasma of blood in which CTCs (CellSearch) were enumerated. The resulting aneuploidy score was correlated with categorized CTC count and associated with outcome. The aneuploidy score was significantly correlated with CTC count, but discordance was observed in 31.6% when applying cut-offs of 5. In both cohorts, aneuploidy score was a significant prognostic marker for both PFS and OS. In the Cox regression models, the HR for aneuploidy score for PFS was 2.52 (95% CI: 1.56–4.07), and the HR for OS was 2.37 (95% CI: 1.36–4.14). Results presented here warrant further investigations into the clinical utility of this marker in MBC patients.",

author = "Noortje Verschoor and {de Weerd}, Vanja and Van, {Mai N.} and Jaco Kraan and Marcel Smid and Heijns, {Joan B.} and Drooger, {Jan C.} and Zuetenhorst, {Johanna M.} and {van der Padt-Pruijsten}, Annemieke and Agnes Jager and Stefan Sleijfer and Martens, {John W.M.} and Wilting, {Saskia M.}",

note = "Funding Information: We express our gratitude to all women who contributed their specimens to the Liquid Biobank and Caremore-AI trials. Furthermore, we would like to thank all our collaborators that included women in these trials. This trial was funded by EU-FP7, Project number 601760-2, and by the Dutch Cancer Society (KWF), grant number 12481. The current study was presented as a poster presentation (P2-03-14) at the San Antonio Breast Cancer Symposium, December 6–10, 2022, in San Antonio, Texas. Publisher Copyright: {\textcopyright} 2023, The Author(s).",

year = "2023",

month = jul,

day = "14",

doi = "10.1038/s41523-023-00563-w",

language = "English",

volume = "9",

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Verschoor, N , de Weerd, V , Van, MN , Kraan, J , Smid, M, Heijns, JB, Drooger, JC, Zuetenhorst, JM, van der Padt-Pruijsten, A, Jager, A , Sleijfer, S , Martens, JWM & Wilting, SM 2023, 'Tumor-agnostic ctDNA levels by mFAST-SeqS in first-line HR-positive, HER2 negative metastatic breast cancer patients as a biomarker for survival', npj Breast Cancer, vol. 9, no. 1, 61. https://doi.org/10.1038/s41523-023-00563-w

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T1 - Tumor-agnostic ctDNA levels by mFAST-SeqS in first-line HR-positive, HER2 negative metastatic breast cancer patients as a biomarker for survival

AU - Verschoor, Noortje

AU - de Weerd, Vanja

AU - Van, Mai N.

AU - Kraan, Jaco

AU - Smid, Marcel

AU - Heijns, Joan B.

AU - Drooger, Jan C.

AU - Zuetenhorst, Johanna M.

AU - van der Padt-Pruijsten, Annemieke

AU - Jager, Agnes

AU - Sleijfer, Stefan

AU - Martens, John W.M.

AU - Wilting, Saskia M.

N1 - Funding Information: We express our gratitude to all women who contributed their specimens to the Liquid Biobank and Caremore-AI trials. Furthermore, we would like to thank all our collaborators that included women in these trials. This trial was funded by EU-FP7, Project number 601760-2, and by the Dutch Cancer Society (KWF), grant number 12481. The current study was presented as a poster presentation (P2-03-14) at the San Antonio Breast Cancer Symposium, December 6–10, 2022, in San Antonio, Texas. Publisher Copyright: © 2023, The Author(s).

PY - 2023/7/14

Y1 - 2023/7/14

N2 - This prospective cohort study reports aneuploidy score by mFast-SeqS as a strong prognostic marker in MBC patients. mFAST-SeqS is an affordable and easily implementable method for the assessment of total ctDNA levels and, as such, provides an alternative prognostic tool. One mixed cohort (cohort A, n = 45) starting any type of treatment in any line of therapy and one larger cohort (cohort B, n = 129) consisting of patients starting aromatase inhibitors (AI) as first-line therapy were used. mFAST-SeqS was performed using plasma of blood in which CTCs (CellSearch) were enumerated. The resulting aneuploidy score was correlated with categorized CTC count and associated with outcome. The aneuploidy score was significantly correlated with CTC count, but discordance was observed in 31.6% when applying cut-offs of 5. In both cohorts, aneuploidy score was a significant prognostic marker for both PFS and OS. In the Cox regression models, the HR for aneuploidy score for PFS was 2.52 (95% CI: 1.56–4.07), and the HR for OS was 2.37 (95% CI: 1.36–4.14). Results presented here warrant further investigations into the clinical utility of this marker in MBC patients.

AB - This prospective cohort study reports aneuploidy score by mFast-SeqS as a strong prognostic marker in MBC patients. mFAST-SeqS is an affordable and easily implementable method for the assessment of total ctDNA levels and, as such, provides an alternative prognostic tool. One mixed cohort (cohort A, n = 45) starting any type of treatment in any line of therapy and one larger cohort (cohort B, n = 129) consisting of patients starting aromatase inhibitors (AI) as first-line therapy were used. mFAST-SeqS was performed using plasma of blood in which CTCs (CellSearch) were enumerated. The resulting aneuploidy score was correlated with categorized CTC count and associated with outcome. The aneuploidy score was significantly correlated with CTC count, but discordance was observed in 31.6% when applying cut-offs of 5. In both cohorts, aneuploidy score was a significant prognostic marker for both PFS and OS. In the Cox regression models, the HR for aneuploidy score for PFS was 2.52 (95% CI: 1.56–4.07), and the HR for OS was 2.37 (95% CI: 1.36–4.14). Results presented here warrant further investigations into the clinical utility of this marker in MBC patients.

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Tumor-agnostic ctDNA levels by mFAST-SeqS in first-line HR-positive, HER2 negative metastatic breast cancer patients as a biomarker for survival

Abstract

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