RT Journal Article SR Electronic T1 Capecitabine Efficacy Is Correlated with TYMP and RB1 Expression in PDX Established from Triple-Negative Breast Cancers JF Clinical Cancer Research JO Clin Cancer Res FD American Association for Cancer Research SP 2605 OP 2615 DO 10.1158/1078-0432.CCR-17-3490 VO 24 IS 11 A1 Marangoni, Elisabetta A1 Laurent, Cécile A1 Coussy, Florence A1 El-Botty, Rania A1 Château-Joubert, Sophie A1 Servely, Jean-Luc A1 de Plater, Ludmilla A1 Assayag, Franck A1 Dahmani, Ahmed A1 Montaudon, Elodie A1 Nemati, Fariba A1 Fleury, Justine A1 Vacher, Sophie A1 Gentien, David A1 Rapinat, Audrey A1 Foidart, Pierre A1 Sounni, Nor Eddine A1 Noel, Agnès A1 Vincent-Salomon, Anne A1 Lae, Marick A1 Decaudin, Didier A1 Roman-Roman, Sergio A1 Bièche, Ivan A1 Piccart, Martine A1 Reyal, Fabien YR 2018 UL http://clincancerres.aacrjournals.org/content/24/11/2605.abstract AB Purpose: Triple-negative breast cancer (TNBC) patients with residual disease after neoadjuvant chemotherapy have a poor outcome. We developed patient-derived xenografts (PDX) from residual tumors to identify efficient chemotherapies and predictive biomarkers in a context of resistance to anthracyclines- and taxanes-based treatments.Experimental Design: PDX were established from residual tumors of primary breast cancer patients treated in neoadjuvant setting. TNBC PDX were treated by anthracyclines, taxanes, platins, and capecitabine. Predictive biomarkers were identified by transcriptomic and immunohistologic analysis. Downregulation of RB1 was performed by siRNA in a cell line established from a PDX.Results: Residual TNBC PDX were characterized by a high tumor take, a short latency, and a poor prognosis of the corresponding patients. With the exception of BRCA1/2-mutated models, residual PDX were resistant to anthracyclines, taxanes, and platins. Capecitabine, the oral prodrug of 5-FU, was highly efficient in 60% of PDX, with two models showing complete responses. Prior treatment of a responder PDX with 5-FU increased expression of thymidylate synthase and decreased efficacy of capecitabine. Transcriptomic and IHC analyses of 32 TNBC PDX, including both residual tumors and treatment-naïve derived tumors, identified RB1 and TYMP proteins as predictive biomarkers for capecitabine response. Finally, RB1 knockdown in a cell line established from a capecitabine-responder PDX decreased sensitivity to 5-FU treatment.Conclusions: We identified capecitabine as efficient chemotherapy in TNBC PDX models established from residual disease and resistant to anthracyclines, taxanes, and platins. RB1 positivity and high expression of TYMP were significantly associated with capecitabine response. Clin Cancer Res; 24(11); 2605–15. ©2018 AACR.