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Genomic and transcriptomic analyses of breast cancer primaries and matched metastases in AURORA, the Breast International Group (BIG) molecular screening initiative.

par Aftimos, Philippe ;Oliveira, Mafalda;Irrthum, Alexandre;Fumagalli, Debora ;Sotiriou, Christos ;Nili Gal-Yam, Einav;Robson, Mark ME;Ndozeng, Justin;Di Leo, Angelo;Ciruelos, Eva M;de Azambuja, Evandro ;Viale, Giuseppe;Scheepers, Elsemieke D;Curigliano, Giuseppe;Bliss, Judith M;Reis-Filho, Jorge Sergio;Colleoni, Marco Angelo;Balic, Marija;Cardoso, Fatima ;Albanell, Joan;Duhem, Caroline;Marreaud, Sandrine;Romagnoli, Dario;Rojas, Beatriz;Gombos, Andrea ;Wildiers, Hans;Guerrero-Zotano, Angel;Hall, Peter;Bonetti, Andrea;Larsson, Karolina Fs;Degiorgis, Martina;Khodaverdi, Silvia;Greil, Richard;Sverrisdottir, Asgerdur;Paoli, Marta;Seyll, Ethel ;Loibl, Sibylle;Linderholm, Barbro B.K.;Zoppoli, Gabriele;Davidson, Nancy E;Johannsson, Oskar Th;Bedard, Philippe L;Loi, Sherene ;Knox, Susan;Cameron, David A;Harbeck, Nadia;Lasa Montoya, Maite;Brandão, Mariana;Vingiani, Andrea;Caballero, Carmela;Hilbers, Florentine S;Yates, Lucy R;Benelli, Matteo;Venet, David ;Piccart, Martine J
Référence Cancer discovery
Publication Publié, 2021-06-01

Article révisé par les pairs

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Résumé :

AURORA aims to study the processes of relapse in metastatic breast cancer (MBC) by performing multi-omics profiling on paired primary tumors and early-course metastases. Among 381 patients (primary tumor and metastasis pairs: 252 TGS, 152 RNA-Seq, 67 SNP Arrays), we found a driver role for GATA1 and MEN1 somatic mutations. Metastases were enriched in ESR1, PTEN, CDH1, PIK3CA and RB1 mutations; MDM4, MYC amplifications; ARID1A deletions. An increase in clonality was observed in driver genes like ERBB2 and RB1. Intrinsic subtype switching occurred in 36% of cases. Luminal A/B to HER2-Enriched switching was associated with TP53 and/or PIK3CA mutations. Metastases had lower immune score and increased immune permissive cells. High TMB correlated to shorter time to relapse in HR+/HER2- cancers. ESCAT tier I/II alterations were detected in 51% of patients and matched therapy was used in 7%. Integration of multi-omics analyses in clinical practice could impact treatment strategies in MBC.