The prognostic and predictive value of ESR1 fusion gene transcripts in primary breast cancer
| Autor: | Maurice P.H.M. Jansen, Paolo Vigneri, Stefan Sleijfer, Corine M. Beaufort, Silvia R. Vitale, John Martens, Anieta M. Sieuwerts, Anita M. A. C. Trapman-Jansen, A. Mieke Timmermans, Kirsten Ruigrok-Ritstier, Renée Foekens |
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| Přispěvatelé: | Medical Oncology |
| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
Oncology
Adult Cancer Research medicine.medical_specialty Antineoplastic Agents Hormonal Breast Neoplasms Antineoplastic Agents Fusion genes Disease-Free Survival Fusion gene Breast cancer SDG 3 - Good Health and Well-being Predictive Value of Tests Internal medicine Genetics 80 and over Medicine Humans RC254-282 Aged Proportional Hazards Models Retrospective Studies Aged 80 and over Hormonal business.industry ESR1 RT-qPCR CCDC170 Estrogen Receptor alpha Neoplasms. Tumors. Oncology. Including cancer and carcinogens Middle Aged Prognosis Predictive value body regions Case-Control Studies Female Gene Fusion business Primary breast cancer Estrogen receptor alpha |
| Zdroj: | BMC Cancer, Vol 22, Iss 1, Pp 1-16 (2022) BMC Cancer, 22(1):165. BioMed Central Ltd. |
| ISSN: | 1471-2407 |
| Popis: | Background In breast cancer (BC), recurrent fusion genes of estrogen receptor alpha (ESR1) and AKAP12, ARMT1 and CCDC170 have been reported. In these gene fusions the ligand binding domain of ESR1 has been replaced by the transactivation domain of the fusion partner constitutively activating the receptor. As a result, these gene fusions can drive tumor growth hormone independently as been shown in preclinical models, but the clinical value of these fusions have not been reported. Here, we studied the prognostic and predictive value of different frequently reported ESR1 fusion transcripts in primary BC. Methods We evaluated 732 patients with primary BC (131 ESR1-negative and 601 ESR1-positive cases), including two ER-positive BC patient cohorts: one cohort of 322 patients with advanced disease who received first-line endocrine therapy (ET) (predictive cohort), and a second cohort of 279 patients with lymph node negative disease (LNN) who received no adjuvant systemic treatment (prognostic cohort). Fusion gene transcript levels were measured by reverse transcriptase quantitative PCR. The presence of the different fusion transcripts was associated, in uni- and multivariable Cox regression analysis taking along current clinico-pathological characteristics, to progression free survival (PFS) during first-line endocrine therapy in the predictive cohort, and disease- free survival (DFS) and overall survival (OS) in the prognostic cohort. Results The ESR1-CCDC170 fusion transcript was present in 27.6% of the ESR1-positive BC subjects and in 2.3% of the ESR1-negative cases. In the predictive cohort, none of the fusion transcripts were associated with response to first-line ET. In the prognostic cohort, the median DFS and OS were respectively 37 and 93 months for patients with an ESR1-CCDC170 exon 8 gene fusion transcript and respectively 91 and 212 months for patients without this fusion transcript. In a multivariable analysis, this ESR1-CCDC170 fusion transcript was an independent prognostic factor for DFS (HR) (95% confidence interval (CI): 1.8 (1.2–2.8), P = 0.005) and OS (HR (95% CI: 1.7 (1.1–2.7), P = 0.023). Conclusions Our study shows that in primary BC only ESR1-CCDC170 exon 8 gene fusion transcript carries prognostic value. None of the ESR1 fusion transcripts, which are considered to have constitutive ER activity, was predictive for outcome in BC with advanced disease treated with endocrine treatment. |
| Databáze: | OpenAIRE |
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