Article (Scientific journals)
Genomic aberrations and late recurrence in postmenopausal women with hormone receptor-positive early breast cancer: Results from the SOLE Trial.
Guerini-Rocco, Elena; Gray, Kathryn P.; Fumagalli, Caterina et al.
2020In Clinical cancer research : an official journal of the American Association for Cancer Research
Peer reviewed
 

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Keywords :
oncology
Abstract :
[en] PURPOSE: Women with hormone-receptor-positive early breast cancers have a persistent risk of relapse and biomarkers for late recurrence are needed. We sought to identify tumor genomic aberrations associated with increased late recurrence risk. EXPERIMENTAL DESIGN: In a secondary analysis of Study of Letrozole Extension (SOLE) trial, a case-cohort-like sampling selected 598 primary breast cancer for targeted next-generation sequencing (NGS) analysis of gene mutations and copy number gains (CNG). Correlations of genomic aberrations with clinicopathologic factors and breast and distant recurrence free-intervals (BCFI and DRFI) were analyzed using weighted Cox models. RESULTS: Analysis of mutations and CNG was successfully performed for 403 and 350 samples, including 148 and 134 patients with breast cancer recurrences (median follow-up time: 5.2 years), respectively. The most frequent alterations were PIK3CA mutations (42%) and CNGs of CCND1 (15%), ERBB2 (10%), FGFR1 (8%) and MYC (8%). PIK3CA mutations and MYC CNG were associated with lower (p=0.03) and higher (p=0.004) tumor grade respectively; a higher Ki67 was seen in tumor with CCND1, ERBB2 and MYC CNGs (p=0.01, <0.001 and 0.03 respectively). FGFR1 CNG was associated with an increased risk of late events in univariate analyses (17/29 patients; BCFI: HR=3.2, 95%CI: 1.48-6.92, p =0.003; DRFI: HR=3.5, 95%CI: 1.61-7.75, p=0.002) and in multivariable models adjusted for clinicopathologic factors. CONCLUSIONS: Postmenopausal women with hormone receptor-positive early breast cancer harboring FGFR1 CNG had an increased risk of late recurrence despite extended therapy. FGFR1 CNG may represent a useful prognostic biomarker for late recurrence and a therapeutic target.
Disciplines :
Oncology
Author, co-author :
Guerini-Rocco, Elena
Gray, Kathryn P.
Fumagalli, Caterina
Reforgiato, Marta Rita
Leone, Isabella
Rafaniello Raviele, Paola
Munzone, Elisabetta
Kammler, Roswitha
Neven, Patrick
Hitre, Erika
Jerusalem, Guy  ;  Université de Liège - ULiège > Département des sciences cliniques > Oncologie
Simoncini, Edda L.
Gombos, Andrea
Deleu, Ines
Karlsson, Per
Aebi, Stefan
Chirgwin, Jacquie
Di Lauro, Vincenzo
Thompson, Alastair M.
Graas, Marie-Pascale
Barber, Matthew
Fontaine, Christel
Loibl, Sibylle
Gavilá, Joaquín
Kuroi, Katsumasa
Müller, Bettina
O'Reilly, Seamus
Di Leo, Angelo
Goldhirsch, Aron
Viale, Giuseppe
Barberis, Massimo
Regan, Meredith M.
Colleoni, Marco
More authors (23 more) Less
Language :
English
Title :
Genomic aberrations and late recurrence in postmenopausal women with hormone receptor-positive early breast cancer: Results from the SOLE Trial.
Publication date :
October 2020
Journal title :
Clinical cancer research : an official journal of the American Association for Cancer Research
ISSN :
1078-0432
Peer reviewed :
Peer reviewed
Commentary :
Copyright ©2020, American Association for Cancer Research.
Available on ORBi :
since 10 November 2020

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