Genomic Aberrations and Late Recurrence in Postmenopausal Women with Hormone Receptor-positive Early Breast Cancer: Results from the SOLE Trial.

Autor:	Guerini-Rocco E; Division of Pathology and Laboratory Medicine, IEO, European Institute of Oncology IRCCS, Milan and University of Milan, Department of Oncology and Hemato-Oncology, Milan, Italy. Elena.GueriniRocco@ieo.it., Gray KP; International Breast Cancer Study Group Statistical Center, Frontier Science Foundation, and Harvard T.H. Chan School of Public Health, Boston, Massachusetts., Fumagalli C; Division of Pathology and Laboratory Medicine, IEO, European Institute of Oncology IRCCS, Milan, Italy., Reforgiato MR; Division of Pathology and Laboratory Medicine, IEO, European Institute of Oncology IRCCS, Milan, Italy., Leone I; Division of Pathology and Laboratory Medicine, IEO, European Institute of Oncology IRCCS, Milan, Italy., Rafaniello Raviele P; Division of Pathology and Laboratory Medicine, IEO, European Institute of Oncology IRCCS, Milan, Italy., Munzone E; Division of Medical Senology, IEO, European Institute of Oncology IRCCS, Milan, Italy., Kammler R; International Breast Cancer Study Group, Bern, Switzerland., Neven P; Multidisciplinary Breast Center, University Hospitals, KU Leuven, Leuven, Belgium., Hitre E; National Institute of Oncology, Budapest, Hungary., Jerusalem G; CHU Liège and Liège University, Liège, Belgium., Simoncini E; ASST Spedali Civili di Brescia, Brescia, Italy., Gombos A; Institute Jules Bordet, Brussels, Belgium., Deleu I; AZ Nikolaas, Sint-Niklaas, Belgium., Karlsson P; Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy/Sahlgrenska University Hospital, University of Gothenburg, Gothenburg, Sweden., Aebi S; Lucerne Cantonal Hospital and University of Bern, Bern, Switzerland., Chirgwin J; Box Hill and Maroondah Hospitals, Monash University, Melbourne, Victoria, Australia., Di Lauro V; CRO-Aviano, Aviano, Italy., Thompson A; Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, Texas., Graas MP; CHC Clinique St. Joseph, Liège, Belgium., Barber M; Western General Hospital, Edinburgh, Scotland., Fontaine C; UZ Brussel, Brussels, Belgium., Loibl S; German Breast Group, Neu-Isenburg, Germany., Gavilá J; Fundación Instituto Valenciano de Oncologia, Valencia, Spain., Kuroi K; Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Bunkyo City, Tokyo, Japan., Müller B; Chilean Cooperative Group for Oncologic Research (GOCCHI), Santiago, Chile., O'Reilly S; Cancer Trials Ireland, Glasnevin, Dublin, Ireland., Di Leo A; Hospital of Prato-AUSL Toscana Centro, Prato, Italy., Goldhirsch A; International Breast Cancer Study Group, Bern, Switzerland and MultiMedica, Milan, Italy., Viale G; Division of Pathology and Laboratory Medicine, IEO, European Institute of Oncology IRCCS, Milan, International Breast Cancer Study Group Central Pathology Office and University of Milan, Department of Oncology and Hemato-Oncology, Milan, Italy., Barberis M; Division of Pathology and Laboratory Medicine, IEO, European Institute of Oncology IRCCS, Milan, Italy., Regan MM; International Breast Cancer Study Group Statistical Center, Dana-Farber Cancer Institute, and Harvard Medical School, Boston, Massachusetts., Colleoni M; Division of Medical Senology, European Institute of Oncology, and the International Breast Cancer Study Group, Milan, Italy.
Jazyk:	angličtina
Zdroj:	Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2021 Jan 15; Vol. 27 (2), pp. 504-512. Date of Electronic Publication: 2020 Oct 20.
DOI:	10.1158/1078-0432.CCR-20-0126
Abstrakt:	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 trial, a case-cohort-like sampling selected 598 primary breast cancers for targeted next-generation sequencing analysis of gene mutations and copy-number gains (CNGs). Correlations of genomic aberrations with clinicopathologic factors and breast and distant recurrence-free intervals (BCFIs and DRFIs) were analyzed using weighted Cox models. Results: Analysis of mutations and CNGs 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 CNGs were associated with lower ( P = 0.03) and higher ( P = 0.004) tumor grade, respectively; a higher Ki-67 was seen in tumor with CCND1, ERBB2 , and MYC CNGs ( P = 0.01, P < 0.001, and P = 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% confidence interval (CI), 1.48-6.92; P = 0.003 and 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. (©2020 American Association for Cancer Research.)
Databáze:	MEDLINE
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