Circulating Tumor Cells in Breast Cancer Patients Treated by Neoadjuvant Chemotherapy: A Meta-analysis

François-Clément Bidard; Stefan Michiels; Sabine Riethdorf; Volkmar Mueller; Laura J Esserman; Anthony Lucci; Bjørn Naume; Jun Horiguchi; Rafael Gisbert-Criado; Stefan Sleijfer; Masakazu Toi; Jose A Garcia-Saenz; Andreas Hartkopf; Daniele Generali; Françoise Rothé; Jeffrey Smerage; Laura Muinelo-Romay; Justin Stebbing; Patrice Viens; Mark Jesus M Magbanua; Carolyn S Hall; Olav Engebraaten; Daisuke Takata; José Vidal-Martínez; Wendy Onstenk; Noriyoshi Fujisawa; Eduardo Diaz-Rubio; Florin-Andrei Taran; Maria Rosa Cappelletti; Michail Ignatiadis; Charlotte Proudhon; Denise M Wolf; Jessica B Bauldry; Elin Borgen; Rin Nagaoka; Vicente Carañana; Jaco Kraan; Marisa Maestro; Sara Yvonne Brucker; Karsten Weber; Fabien Reyal; Dominic Amara; Mandar G Karhade; Randi R Mathiesen; Hideaki Tokiniwa; Antonio Llombart-Cussac; Alessandra Meddis; Paul Blanche; Koenraad d'Hollander; Paul Cottu; John W Park; Sibylle Loibl; Aurélien Latouche; Jean-Yves Pierga; Klaus Pantel

doi:10.1093/jnci/djy018

Circulating Tumor Cells in Breast Cancer Patients Treated by Neoadjuvant Chemotherapy: A Meta-analysis

François-Clément Bidard, Stefan Michiels, Sabine Riethdorf, Volkmar Mueller, Laura J Esserman, Anthony Lucci, Bjørn Naume, Jun Horiguchi, Rafael Gisbert-Criado, Stefan Sleijfer, Masakazu Toi, Jose A Garcia-Saenz, Andreas Hartkopf, Daniele Generali, Françoise Rothé, Jeffrey Smerage, Laura Muinelo-Romay, Justin Stebbing, Patrice Viens, Mark Jesus M MagbanuaCarolyn S Hall, Olav Engebraaten, Daisuke Takata, José Vidal-Martínez, Wendy Onstenk, Noriyoshi Fujisawa, Eduardo Diaz-Rubio, Florin-Andrei Taran, Maria Rosa Cappelletti, Michail Ignatiadis, Charlotte Proudhon, Denise M Wolf, Jessica B Bauldry, Elin Borgen, Rin Nagaoka, Vicente Carañana, Jaco Kraan, Marisa Maestro, Sara Yvonne Brucker, Karsten Weber, Fabien Reyal, Dominic Amara, Mandar G Karhade, Randi R Mathiesen, Hideaki Tokiniwa, Antonio Llombart-Cussac, Alessandra Meddis, Paul Blanche, Koenraad d'Hollander, Paul Cottu, John W Park, Sibylle Loibl, Aurélien Latouche, Jean-Yves Pierga, Klaus Pantel

Section of Biostatistics

103 Citations (Scopus)

Abstract

Background: We conducted a meta-analysis in nonmetastatic breast cancer patients treated by neoadjuvant chemotherapy (NCT) to assess the clinical validity of circulating tumor cell (CTC) detection as a prognostic marker. Methods: We collected individual patient data from 21 studies in which CTC detection by CellSearch was performed in early breast cancer patients treated with NCT. The primary end point was overall survival, analyzed according to CTC detection, using Cox regression models stratified by study. Secondary end points included distant disease-free survival, locoregional relapse-free interval, and pathological complete response. All statistical tests were two-sided. Results: Data from patients were collected before NCT (n ¼ 1574) and before surgery (n ¼ 1200). CTC detection revealed one or more CTCs in 25.2% of patients before NCT; this was associated with tumor size (P < .001). The number of CTCs detected had a detrimental and decremental impact on overall survival (P < .001), distant disease-free survival (P < .001), and locoregional relapse-free interval (P < .001), but not on pathological complete response. Patients with one, two, three to four, and five or more CTCs before NCT displayed hazard ratios of death of 1.09 (95% confidence interval [CI] ¼ 0.65 to 1.69), 2.63 (95% CI ¼ 1.42 to 4.54), 3.83 (95% CI ¼ 2.08 to 6.66), and 6.25 (95% CI ¼ 4.34 to 9.09), respectively. In 861 patients with full data available, adding CTC detection before NCT increased the prognostic ability of multivariable prognostic models for overall survival (P < .001), distant disease-free survival (P < .001), and locoregional relapse-free interval (P ¼ .008). Conclusions: CTC count is an independent and quantitative prognostic factor in early breast cancer patients treated by NCT. It complements current prognostic models based on tumor characteristics and response to therapy.

Original language	English
Journal	National Cancer Institute. Journal (Print)
Volume	110
Issue number	6
Pages (from-to)	560-567
Number of pages	8
ISSN	0027-8874
DOIs	https://doi.org/10.1093/jnci/djy018
Publication status	Published - 1 Jun 2018

UN SDGs

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

Access to Document

10.1093/jnci/djy018

djy018.pdfFinal published version, 979 KB

Cite this

Bidard, F.-C., Michiels, S., Riethdorf, S., Mueller, V., Esserman, L. J., Lucci, A., Naume, B., Horiguchi, J., Gisbert-Criado, R., Sleijfer, S., Toi, M., Garcia-Saenz, J. A., Hartkopf, A., Generali, D., Rothé, F., Smerage, J., Muinelo-Romay, L., Stebbing, J., Viens, P., ... Pantel, K. (2018). Circulating Tumor Cells in Breast Cancer Patients Treated by Neoadjuvant Chemotherapy: A Meta-analysis. National Cancer Institute. Journal (Print), 110(6), 560-567. https://doi.org/10.1093/jnci/djy018

Bidard, F-C, Michiels, S, Riethdorf, S, Mueller, V, Esserman, LJ, Lucci, A, Naume, B, Horiguchi, J, Gisbert-Criado, R, Sleijfer, S, Toi, M, Garcia-Saenz, JA, Hartkopf, A, Generali, D, Rothé, F, Smerage, J, Muinelo-Romay, L, Stebbing, J, Viens, P, Magbanua, MJM, Hall, CS, Engebraaten, O, Takata, D, Vidal-Martínez, J, Onstenk, W, Fujisawa, N, Diaz-Rubio, E, Taran, F-A, Cappelletti, MR, Ignatiadis, M, Proudhon, C, Wolf, DM, Bauldry, JB, Borgen, E, Nagaoka, R, Carañana, V, Kraan, J, Maestro, M, Brucker, SY, Weber, K, Reyal, F, Amara, D, Karhade, MG, Mathiesen, RR, Tokiniwa, H, Llombart-Cussac, A, Meddis, A, Blanche, P, d'Hollander, K, Cottu, P, Park, JW, Loibl, S, Latouche, A, Pierga, J-Y & Pantel, K 2018, 'Circulating Tumor Cells in Breast Cancer Patients Treated by Neoadjuvant Chemotherapy: A Meta-analysis', National Cancer Institute. Journal (Print), vol. 110, no. 6, pp. 560-567. https://doi.org/10.1093/jnci/djy018

@article{752b3b8867974e3897e1a3340d2805b0,

title = "Circulating Tumor Cells in Breast Cancer Patients Treated by Neoadjuvant Chemotherapy: A Meta-analysis",

abstract = "Background: We conducted a meta-analysis in nonmetastatic breast cancer patients treated by neoadjuvant chemotherapy (NCT) to assess the clinical validity of circulating tumor cell (CTC) detection as a prognostic marker. Methods: We collected individual patient data from 21 studies in which CTC detection by CellSearch was performed in early breast cancer patients treated with NCT. The primary end point was overall survival, analyzed according to CTC detection, using Cox regression models stratified by study. Secondary end points included distant disease-free survival, locoregional relapse-free interval, and pathological complete response. All statistical tests were two-sided. Results: Data from patients were collected before NCT (n ¼ 1574) and before surgery (n ¼ 1200). CTC detection revealed one or more CTCs in 25.2% of patients before NCT; this was associated with tumor size (P < .001). The number of CTCs detected had a detrimental and decremental impact on overall survival (P < .001), distant disease-free survival (P < .001), and locoregional relapse-free interval (P < .001), but not on pathological complete response. Patients with one, two, three to four, and five or more CTCs before NCT displayed hazard ratios of death of 1.09 (95% confidence interval [CI] ¼ 0.65 to 1.69), 2.63 (95% CI ¼ 1.42 to 4.54), 3.83 (95% CI ¼ 2.08 to 6.66), and 6.25 (95% CI ¼ 4.34 to 9.09), respectively. In 861 patients with full data available, adding CTC detection before NCT increased the prognostic ability of multivariable prognostic models for overall survival (P < .001), distant disease-free survival (P < .001), and locoregional relapse-free interval (P ¼ .008). Conclusions: CTC count is an independent and quantitative prognostic factor in early breast cancer patients treated by NCT. It complements current prognostic models based on tumor characteristics and response to therapy.",

author = "Fran{\c c}ois-Cl{\'e}ment Bidard and Stefan Michiels and Sabine Riethdorf and Volkmar Mueller and Esserman, {Laura J} and Anthony Lucci and Bj{\o}rn Naume and Jun Horiguchi and Rafael Gisbert-Criado and Stefan Sleijfer and Masakazu Toi and Garcia-Saenz, {Jose A} and Andreas Hartkopf and Daniele Generali and Fran{\c c}oise Roth{\'e} and Jeffrey Smerage and Laura Muinelo-Romay and Justin Stebbing and Patrice Viens and Magbanua, {Mark Jesus M} and Hall, {Carolyn S} and Olav Engebraaten and Daisuke Takata and Jos{\'e} Vidal-Mart{\'i}nez and Wendy Onstenk and Noriyoshi Fujisawa and Eduardo Diaz-Rubio and Florin-Andrei Taran and Cappelletti, {Maria Rosa} and Michail Ignatiadis and Charlotte Proudhon and Wolf, {Denise M} and Bauldry, {Jessica B} and Elin Borgen and Rin Nagaoka and Vicente Cara{\~n}ana and Jaco Kraan and Marisa Maestro and Brucker, {Sara Yvonne} and Karsten Weber and Fabien Reyal and Dominic Amara and Karhade, {Mandar G} and Mathiesen, {Randi R} and Hideaki Tokiniwa and Antonio Llombart-Cussac and Alessandra Meddis and Paul Blanche and Koenraad d'Hollander and Paul Cottu and Park, {John W} and Sibylle Loibl and Aur{\'e}lien Latouche and Jean-Yves Pierga and Klaus Pantel",

year = "2018",

month = jun,

day = "1",

doi = "10.1093/jnci/djy018",

language = "English",

volume = "110",

pages = "560--567",

journal = "National Cancer Institute. Journal (Print)",

issn = "0027-8874",

publisher = "Oxford University Press",

number = "6",

}

TY - JOUR

T1 - Circulating Tumor Cells in Breast Cancer Patients Treated by Neoadjuvant Chemotherapy

T2 - A Meta-analysis

AU - Bidard, François-Clément

AU - Michiels, Stefan

AU - Riethdorf, Sabine

AU - Mueller, Volkmar

AU - Esserman, Laura J

AU - Lucci, Anthony

AU - Naume, Bjørn

AU - Horiguchi, Jun

AU - Gisbert-Criado, Rafael

AU - Sleijfer, Stefan

AU - Toi, Masakazu

AU - Garcia-Saenz, Jose A

AU - Hartkopf, Andreas

AU - Generali, Daniele

AU - Rothé, Françoise

AU - Smerage, Jeffrey

AU - Muinelo-Romay, Laura

AU - Stebbing, Justin

AU - Viens, Patrice

AU - Magbanua, Mark Jesus M

AU - Hall, Carolyn S

AU - Engebraaten, Olav

AU - Takata, Daisuke

AU - Vidal-Martínez, José

AU - Onstenk, Wendy

AU - Fujisawa, Noriyoshi

AU - Diaz-Rubio, Eduardo

AU - Taran, Florin-Andrei

AU - Cappelletti, Maria Rosa

AU - Ignatiadis, Michail

AU - Proudhon, Charlotte

AU - Wolf, Denise M

AU - Bauldry, Jessica B

AU - Borgen, Elin

AU - Nagaoka, Rin

AU - Carañana, Vicente

AU - Kraan, Jaco

AU - Maestro, Marisa

AU - Brucker, Sara Yvonne

AU - Weber, Karsten

AU - Reyal, Fabien

AU - Amara, Dominic

AU - Karhade, Mandar G

AU - Mathiesen, Randi R

AU - Tokiniwa, Hideaki

AU - Llombart-Cussac, Antonio

AU - Meddis, Alessandra

AU - Blanche, Paul

AU - d'Hollander, Koenraad

AU - Cottu, Paul

AU - Park, John W

AU - Loibl, Sibylle

AU - Latouche, Aurélien

AU - Pierga, Jean-Yves

AU - Pantel, Klaus

PY - 2018/6/1

Y1 - 2018/6/1

N2 - Background: We conducted a meta-analysis in nonmetastatic breast cancer patients treated by neoadjuvant chemotherapy (NCT) to assess the clinical validity of circulating tumor cell (CTC) detection as a prognostic marker. Methods: We collected individual patient data from 21 studies in which CTC detection by CellSearch was performed in early breast cancer patients treated with NCT. The primary end point was overall survival, analyzed according to CTC detection, using Cox regression models stratified by study. Secondary end points included distant disease-free survival, locoregional relapse-free interval, and pathological complete response. All statistical tests were two-sided. Results: Data from patients were collected before NCT (n ¼ 1574) and before surgery (n ¼ 1200). CTC detection revealed one or more CTCs in 25.2% of patients before NCT; this was associated with tumor size (P < .001). The number of CTCs detected had a detrimental and decremental impact on overall survival (P < .001), distant disease-free survival (P < .001), and locoregional relapse-free interval (P < .001), but not on pathological complete response. Patients with one, two, three to four, and five or more CTCs before NCT displayed hazard ratios of death of 1.09 (95% confidence interval [CI] ¼ 0.65 to 1.69), 2.63 (95% CI ¼ 1.42 to 4.54), 3.83 (95% CI ¼ 2.08 to 6.66), and 6.25 (95% CI ¼ 4.34 to 9.09), respectively. In 861 patients with full data available, adding CTC detection before NCT increased the prognostic ability of multivariable prognostic models for overall survival (P < .001), distant disease-free survival (P < .001), and locoregional relapse-free interval (P ¼ .008). Conclusions: CTC count is an independent and quantitative prognostic factor in early breast cancer patients treated by NCT. It complements current prognostic models based on tumor characteristics and response to therapy.

AB - Background: We conducted a meta-analysis in nonmetastatic breast cancer patients treated by neoadjuvant chemotherapy (NCT) to assess the clinical validity of circulating tumor cell (CTC) detection as a prognostic marker. Methods: We collected individual patient data from 21 studies in which CTC detection by CellSearch was performed in early breast cancer patients treated with NCT. The primary end point was overall survival, analyzed according to CTC detection, using Cox regression models stratified by study. Secondary end points included distant disease-free survival, locoregional relapse-free interval, and pathological complete response. All statistical tests were two-sided. Results: Data from patients were collected before NCT (n ¼ 1574) and before surgery (n ¼ 1200). CTC detection revealed one or more CTCs in 25.2% of patients before NCT; this was associated with tumor size (P < .001). The number of CTCs detected had a detrimental and decremental impact on overall survival (P < .001), distant disease-free survival (P < .001), and locoregional relapse-free interval (P < .001), but not on pathological complete response. Patients with one, two, three to four, and five or more CTCs before NCT displayed hazard ratios of death of 1.09 (95% confidence interval [CI] ¼ 0.65 to 1.69), 2.63 (95% CI ¼ 1.42 to 4.54), 3.83 (95% CI ¼ 2.08 to 6.66), and 6.25 (95% CI ¼ 4.34 to 9.09), respectively. In 861 patients with full data available, adding CTC detection before NCT increased the prognostic ability of multivariable prognostic models for overall survival (P < .001), distant disease-free survival (P < .001), and locoregional relapse-free interval (P ¼ .008). Conclusions: CTC count is an independent and quantitative prognostic factor in early breast cancer patients treated by NCT. It complements current prognostic models based on tumor characteristics and response to therapy.

U2 - 10.1093/jnci/djy018

DO - 10.1093/jnci/djy018

M3 - Journal article

C2 - 29659933

SN - 0027-8874

VL - 110

SP - 560

EP - 567

JO - National Cancer Institute. Journal (Print)

JF - National Cancer Institute. Journal (Print)

IS - 6

ER -

Circulating Tumor Cells in Breast Cancer Patients Treated by Neoadjuvant Chemotherapy: A Meta-analysis

Abstract

UN SDGs

Access to Document

Fingerprint

Cite this