Circulating tumor cells in breast cancer patients treated by neoadjuvant chemotherapy: A Meta-analysis

55siBACKGROUND: 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.reservedmixedFrançois-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 PantelBidard, François-Clément; Michiels, Stefan; Riethdorf, Sabine; Mueller, Volkmar; Esserman, Laura J.; Lucci, Anthony; Naume, Bjørn; Horiguchi, Jun; Gisbert-Criado, Rafael; Sleijfer, Stefan; Toi, Masakazu; Garcia-Saenz, Jose A.; Hartkopf, Andreas; Generali, Daniele; Rothé, Françoise; Smerage, Jeffrey; Muinelo-Romay, Laura; Stebbing, Justin; Viens, Patrice; Magbanua, Mark Jesus M.; Hall, Carolyn S.; Engebraaten, Olav; Takata, Daisuke; Vidal-Martínez, José; Onstenk, Wendy; Fujisawa, Noriyoshi; Diaz-Rubio, Eduardo; Taran, Florin-Andrei; Rosa Cappelletti, Maria; Ignatiadis, Michail; Proudhon, Charlotte; Wolf, Denise M.; Bauldry, Jessica B.; Borgen, Elin; Nagaoka, Rin; Carañana, Vicente; Kraan, Jaco; Maestro, Marisa; Yvonne Brucker, Sara; Weber, Karsten; Reyal, Fabien; Amara, Dominic; Karhade, Mandar G.; Mathiesen, Randi R.; Tokiniwa, Hideaki; Llombart-Cussac, Antonio; Meddis, Alessandra; Blanche, Paul; D'Hollander, Koenraad; Cottu, Paul; Park, John W.; Loibl, Sibylle; Latouche, Aurélien; Pierga, Jean-Yves; Pantel, Klau