SNP of Aromatase Predict Long-term Survival and Aromatase Inhibitor Toxicity in Patients with Early Breast Cancer: A Biomarker Analysis of the GIM4 and GIM5 Trials.

Autor:	Conte B; Translational Genomics and Targeted Therapies in Solid Tumors, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain.; Department of Medical Oncology, Hospital Clinic of Barcelona, Barcelona, Spain.; Universitat de Barcelona, Barcelona, Spain., Boni L; S.C. Epidemiologia Clinica, IRCCS Ospedale Policlinico San Martino, Genova, Italy., Bisagni G; Azienda unità Sanitaria Locale - IRCCS di Reggio Emilia, Reggio Emilia, Italy., Durando A; Breast Unit Ospedale S Anna, Citta' della Salute e della Scienza di Torino, Torino, Italy., Sanna G; Azienda Ospedaliera Universitaria - Sassari, Sassari, Italy., Gori S; UOC Oncologia Medica, IRCCS Ospedale Sacro Cuore Don Calabria, Negrar, Verona, Italy., Garrone O; Breast Unit, AO S. Croce e Carle Ospedale di insegnamento, Cuneo, Italy.; Medical Oncology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Milano., Tamberi S; UO Oncologia, Ospedale degli Infermi, Faenza, Italy., De Placido S; Department of Clinical Medicine and Surgery, University of Naples Federico II, Napoli, Italy., Schettini F; Translational Genomics and Targeted Therapies in Solid Tumors, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain.; Department of Medical Oncology, Hospital Clinic of Barcelona, Barcelona, Spain.; Departament de Medicina, Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona, Spain., Pazzola A; Azienda Ospedaliera Universitaria - Sassari, Sassari, Italy., Ponzone R; Candiolo Cancer Institute, FPO-IRCCS, Gynecologic Oncology and Multidisciplinary Outpatient Oncology Clinic, Candiolo, Italy., Montemurro F; Candiolo Cancer Institute, FPO-IRCCS, Gynecologic Oncology and Multidisciplinary Outpatient Oncology Clinic, Candiolo, Italy., Lunardi G; Laboratorio Analisi Chimico-Cliniche, IRCCS-Ospedale Sacro Cuore Don Calabria, Negrar, Verona, Italy., Notaro R; Core Research Laboratory-ISPRO, Firenze, Italy., De Angioletti M; Core Research Laboratory-ISPRO, Firenze, Italy.; National Research Council (CNR) - ICCOM, Firenze, Italy., Turletti A; Breast Unit, ASL Citta' di Torino, Torino, Italy., Mansutti M; Department of Oncology, ASUFC Santa Maria della Misericordia, Udine, Italy., Puglisi F; Department of Medicine, University of Udine, Udine, Italy.; Depatment of Medical Oncology, Centro di Riferimento Oncologico di Aviano IRCCS, Aviano, Italy., Frassoldati A; Department of Morphology, Surgery and Experimental medicine, Clinical Oncology, St. Anna University Hospital, Ferrara, Italy., Porpiglia M; Breast Unit Ospedale S. Anna, AOU Città della Salute e della Scienza di Torino, Torino, Italy., Fabi A; Medical Oncology, IRCCS Regina Elena National Cancer Institute, Roma, Italy., Generali D; Medical Oncology, Azienda Istituti Ospitalieri di Cremona, Cremona, Italy.; Department of Medicine, Surgery and Health Sciences, University of Trieste, Trieste, Italy., Scognamiglio G; Oncologia Medica, Ospedale Valduce, Como, Italy., Rossi M; SOC Oncologia, ASO SS.Antonio e Biagio, Alessandria, Italy., Brasó-Maristany F; Translational Genomics and Targeted Therapies in Solid Tumors, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain., Prat A; Translational Genomics and Targeted Therapies in Solid Tumors, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain.; Department of Medical Oncology, Hospital Clinic of Barcelona, Barcelona, Spain.; Department of Clinical Medicine and Surgery, University of Naples Federico II, Napoli, Italy.; Reveal Genomics, Barcelona, Spain.; Institute of Oncology (IOB)-Hospital Quirónsalud, Barcelona, Spain., Cardinali B; Medical Oncology Department, U.O. Clinica di Oncologia Medica, IRCCS Ospedale Policlinico San Martino, Genova, Italy., Piccioli P; Medical Oncology Department, U.O. Clinica di Oncologia Medica, IRCCS Ospedale Policlinico San Martino, Genova, Italy., Serra M; Laboratory of Clinical and Experimental Immunology, IRCCS Istituto Giannina Gaslini, Genoa, Italy., Lastraioli S; Molecular Diagnostic Unit, IRCCS Ospedale Policlinico San Martino, Genoa, Italy., Bighin C; Medical Oncology Department 2, IRCCS Ospedale Policlinico San Martino, Genova, Italy., Poggio F; Medical Oncology Department 2, IRCCS Ospedale Policlinico San Martino, Genova, Italy., Lambertini M; Medical Oncology Department, U.O. Clinica di Oncologia Medica, IRCCS Ospedale Policlinico San Martino, Genova, Italy.; Department of Internal Medicine and Medical Specialties (DiMI), School of Medicine, University of Genova, Genova, Italy., Del Mastro L; Medical Oncology Department, U.O. Clinica di Oncologia Medica, IRCCS Ospedale Policlinico San Martino, Genova, Italy.; Department of Internal Medicine and Medical Specialties (DiMI), School of Medicine, University of Genova, Genova, Italy.
Jazyk:	angličtina
Zdroj:	Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2023 Dec 15; Vol. 29 (24), pp. 5217-5226.
DOI:	10.1158/1078-0432.CCR-23-1568
Abstrakt:	Purpose: In estrogen receptor-positive (ER+) breast cancer, single-nucleotide polymorphisms (SNP) in the aromatase gene might affect aromatase inhibitors (AI) metabolism and efficacy. Here, we assessed the impact of SNP on prognosis and toxicity of patients receiving adjuvant letrozole. Experimental Design: We enrolled 886 postmenopausal patients in the study. They were treated with letrozole for 2 to 5 years after taking tamoxifen for 2 to 6 years, continuing until they completed 5 to 10 years of therapy. Germline DNA was genotyped for SNP rs4646, rs10046, rs749292, and rs727479. Log-rank test and Cox model were used for disease-free survival (DFS) and overall survival (OS). Cumulative incidence (CI) of breast cancer metastasis was assessed through competing risk analysis, with contralateral breast cancer, second malignancies and non-breast cancer death as competing events. CI of skeletal and cardiovascular events were assessed using DFS events as competing events. Subdistribution HR (sHR) with 95% confidence intervals were calculated through Fine-Gray method. Results: No SNP was associated with DFS. Variants rs10046 [sHR 2.03, (1.04-2.94)], rs749292 [sHR 2.11, (1.12-3.94)], and rs727479 [sHR 2.62, (1.17-5.83)] were associated with breast cancer metastasis. Three groups were identified on the basis of the number of these variants (0, 1, >1). Variant-based groups were associated with breast cancer metastasis (10-year CI 2.5%, 7.6%, 10.7%, P = 0.035) and OS (10-year estimates 96.5%, 93.0%, 89.6%, P = 0.030). Co-occurrence of rs10046 and rs749292 was negatively associated with 10-year CI of skeletal events (3.2% vs. 10%, P = 0.033). A similar association emerged between rs727479 and cardiovascular events (0.3% vs. 2.1%, P = 0.026). Conclusions: SNP of aromatase gene predict risk of metastasis and AI-related toxicity in ER+ early breast cancer, opening an opportunity for better treatment individualization. (©2023 The Authors; Published by the American Association for Cancer Research.)
Databáze:	MEDLINE
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