Tumor-Derived Extracellular Vesicles as Complementary Prognostic Factors to Circulating Tumor Cells in Metastatic Breast Cancer

Afroditi Nanou; Jieling Miao; Frank A.W. Coumans; Emily M. Dolce; Elizabeth Darga; William Barlow; Jeffrey B. Smerage; Costanza Paoletti; Andrew K. Godwin; Lajos Pusztai; Priyanka Sharma; Alastair Thompson; Gabriel N. Hortobagyi; Leon W.M.M. Terstappen; Daniel F. Hayes

doi:10.1200/PO.22.00372

Tumor-Derived Extracellular Vesicles as Complementary Prognostic Factors to Circulating Tumor Cells in Metastatic Breast Cancer

Afroditi Nanou, Jieling Miao, Frank A.W. Coumans, Emily M. Dolce, Elizabeth Darga, William Barlow, Jeffrey B. Smerage, Costanza Paoletti, Andrew K. Godwin, Lajos Pusztai, Priyanka Sharma, Alastair Thompson, Gabriel N. Hortobagyi, Leon W.M.M. Terstappen, Daniel F. Hayes^*

^*Corresponding author for this work

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

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Abstract

PURPOSE

Circulating tumor cells (CTCs) are strongly prognostic for overall survival (OS) in metastatic breast cancer although additional prognostic biomarkers are needed. We evaluated the complementary prognostic value of tumor‐derived extracellular vesicles (tdEVs) next to CTCs.

METHODS

We applied the open-source ACCEPT software to archived CellSearch images from the prospective clinical trial SWOG0500 to enumerate CTCs and tumor-derived extracellular vesicles (tdEVs) before and after one cycle of chemotherapy.

RESULTS

CTCs enumerated by ACCEPT were strongly correlated with classical ocular enumeration (correlation r = 0.98). OS was worse with elevated tdEVs (median OS for high/medium/low groups: 17.1 v 29.0 v 43.3 months; P < .0001). In patients with longer OS by CTC counts (< 5 CTC/7.5 mL blood), elevated tdEV levels were independently associated with poorer OS (multivariable analysis P < .001). OS was also longer for patients with low tdEVs after one cycle of chemotherapy (median OS for high/medium/low group: 10.8 v 17.8 v 26.7; P < .0001).

CONCLUSION

This study highlights the complementary prognostic significance of tdEVs in metastatic breast cancer before and after one cycle of chemotherapy.

Original language	English
Article number	e2200372
Journal	JCO Precision Oncology
Volume	7
DOIs	https://doi.org/10.1200/PO.22.00372
Publication status	Published - Jan 2023

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10.1200/PO.22.00372Licence: CC BY-NC-ND

Nanou-2023-Tumor-derived-extracellular-vesicleFinal published version, 10.3 MBLicence: CC BY-NC-ND

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Nanou, A., Miao, J., Coumans, F. A. W., Dolce, E. M., Darga, E., Barlow, W., Smerage, J. B., Paoletti, C., Godwin, A. K., Pusztai, L., Sharma, P., Thompson, A., Hortobagyi, G. N., Terstappen, L. W. M. M., & Hayes, D. F. (2023). Tumor-Derived Extracellular Vesicles as Complementary Prognostic Factors to Circulating Tumor Cells in Metastatic Breast Cancer. JCO Precision Oncology, 7, Article e2200372. https://doi.org/10.1200/PO.22.00372

@article{0861d665a550465ea3f14559b0b3fffa,

title = "Tumor-Derived Extracellular Vesicles as Complementary Prognostic Factors to Circulating Tumor Cells in Metastatic Breast Cancer",

abstract = "PURPOSECirculating tumor cells (CTCs) are strongly prognostic for overall survival (OS) in metastatic breast cancer although additional prognostic biomarkers are needed. We evaluated the complementary prognostic value of tumor‐derived extracellular vesicles (tdEVs) next to CTCs.METHODSWe applied the open-source ACCEPT software to archived CellSearch images from the prospective clinical trial SWOG0500 to enumerate CTCs and tumor-derived extracellular vesicles (tdEVs) before and after one cycle of chemotherapy.RESULTSCTCs enumerated by ACCEPT were strongly correlated with classical ocular enumeration (correlation r = 0.98). OS was worse with elevated tdEVs (median OS for high/medium/low groups: 17.1 v 29.0 v 43.3 months; P < .0001). In patients with longer OS by CTC counts (< 5 CTC/7.5 mL blood), elevated tdEV levels were independently associated with poorer OS (multivariable analysis P < .001). OS was also longer for patients with low tdEVs after one cycle of chemotherapy (median OS for high/medium/low group: 10.8 v 17.8 v 26.7; P < .0001).CONCLUSIONThis study highlights the complementary prognostic significance of tdEVs in metastatic breast cancer before and after one cycle of chemotherapy.",

author = "Afroditi Nanou and Jieling Miao and Coumans, {Frank A.W.} and Dolce, {Emily M.} and Elizabeth Darga and William Barlow and Smerage, {Jeffrey B.} and Costanza Paoletti and Godwin, {Andrew K.} and Lajos Pusztai and Priyanka Sharma and Alastair Thompson and Hortobagyi, {Gabriel N.} and Terstappen, {Leon W.M.M.} and Hayes, {Daniel F.}",

note = "Financial transaction number: 2500038663 ",

year = "2023",

month = jan,

doi = "10.1200/PO.22.00372",

language = "English",

volume = "7",

journal = "JCO Precision Oncology",

issn = "2473-4284",

publisher = "American Society of Clinical Oncology",

}

Nanou, A, Miao, J, Coumans, FAW, Dolce, EM, Darga, E, Barlow, W, Smerage, JB, Paoletti, C, Godwin, AK, Pusztai, L, Sharma, P, Thompson, A, Hortobagyi, GN, Terstappen, LWMM & Hayes, DF 2023, 'Tumor-Derived Extracellular Vesicles as Complementary Prognostic Factors to Circulating Tumor Cells in Metastatic Breast Cancer', JCO Precision Oncology, vol. 7, e2200372. https://doi.org/10.1200/PO.22.00372

TY - JOUR

T1 - Tumor-Derived Extracellular Vesicles as Complementary Prognostic Factors to Circulating Tumor Cells in Metastatic Breast Cancer

AU - Nanou, Afroditi

AU - Miao, Jieling

AU - Coumans, Frank A.W.

AU - Dolce, Emily M.

AU - Darga, Elizabeth

AU - Barlow, William

AU - Smerage, Jeffrey B.

AU - Paoletti, Costanza

AU - Godwin, Andrew K.

AU - Pusztai, Lajos

AU - Sharma, Priyanka

AU - Thompson, Alastair

AU - Hortobagyi, Gabriel N.

AU - Terstappen, Leon W.M.M.

AU - Hayes, Daniel F.

N1 - Financial transaction number: 2500038663

PY - 2023/1

Y1 - 2023/1

N2 - PURPOSECirculating tumor cells (CTCs) are strongly prognostic for overall survival (OS) in metastatic breast cancer although additional prognostic biomarkers are needed. We evaluated the complementary prognostic value of tumor‐derived extracellular vesicles (tdEVs) next to CTCs.METHODSWe applied the open-source ACCEPT software to archived CellSearch images from the prospective clinical trial SWOG0500 to enumerate CTCs and tumor-derived extracellular vesicles (tdEVs) before and after one cycle of chemotherapy.RESULTSCTCs enumerated by ACCEPT were strongly correlated with classical ocular enumeration (correlation r = 0.98). OS was worse with elevated tdEVs (median OS for high/medium/low groups: 17.1 v 29.0 v 43.3 months; P < .0001). In patients with longer OS by CTC counts (< 5 CTC/7.5 mL blood), elevated tdEV levels were independently associated with poorer OS (multivariable analysis P < .001). OS was also longer for patients with low tdEVs after one cycle of chemotherapy (median OS for high/medium/low group: 10.8 v 17.8 v 26.7; P < .0001).CONCLUSIONThis study highlights the complementary prognostic significance of tdEVs in metastatic breast cancer before and after one cycle of chemotherapy.

AB - PURPOSECirculating tumor cells (CTCs) are strongly prognostic for overall survival (OS) in metastatic breast cancer although additional prognostic biomarkers are needed. We evaluated the complementary prognostic value of tumor‐derived extracellular vesicles (tdEVs) next to CTCs.METHODSWe applied the open-source ACCEPT software to archived CellSearch images from the prospective clinical trial SWOG0500 to enumerate CTCs and tumor-derived extracellular vesicles (tdEVs) before and after one cycle of chemotherapy.RESULTSCTCs enumerated by ACCEPT were strongly correlated with classical ocular enumeration (correlation r = 0.98). OS was worse with elevated tdEVs (median OS for high/medium/low groups: 17.1 v 29.0 v 43.3 months; P < .0001). In patients with longer OS by CTC counts (< 5 CTC/7.5 mL blood), elevated tdEV levels were independently associated with poorer OS (multivariable analysis P < .001). OS was also longer for patients with low tdEVs after one cycle of chemotherapy (median OS for high/medium/low group: 10.8 v 17.8 v 26.7; P < .0001).CONCLUSIONThis study highlights the complementary prognostic significance of tdEVs in metastatic breast cancer before and after one cycle of chemotherapy.

UR - https://doi.org/10.1200/PO.22.00372

U2 - 10.1200/PO.22.00372

DO - 10.1200/PO.22.00372

M3 - Article

SN - 2473-4284

VL - 7

JO - JCO Precision Oncology

JF - JCO Precision Oncology

M1 - e2200372

ER -

Tumor-Derived Extracellular Vesicles as Complementary Prognostic Factors to Circulating Tumor Cells in Metastatic Breast Cancer

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