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

Y1 - 2018

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 = 1574) and before surgery (n = 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] = 0.65 to 1.69), 2.63 (95% CI = 1.42 to 4.54), 3.83 (95% CI = 2.08 to 6.66), and 6.25 (95% CI = 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 = .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 = 1574) and before surgery (n = 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] = 0.65 to 1.69), 2.63 (95% CI = 1.42 to 4.54), 3.83 (95% CI = 2.08 to 6.66), and 6.25 (95% CI = 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 = .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

VL - 110

SP - 560

EP - 567

JO - National Cancer Institute. Journal (Print)

JF - National Cancer Institute. Journal (Print)

SN - 0027-8874

IS - 6

ER -