B Ejlertsen1, J Aldridge2, K V Nielsen3, M M Regan4, K L Henriksen5, A E Lykkesfeldt5, S Müller3, R D Gelber6, K N Price7, B B Rasmussen8, G Viale9, H Mouridsen10. 1. Danish Breast Cancer Cooperative Group Statistical Center; Department of Oncology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. Electronic address: ejlertsen@rh.dk. 2. International Breast Cancer Study Group Statistical Center, Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, USA. 3. Dako A/S, Glostrup, Denmark. 4. International Breast Cancer Study Group Statistical Center, Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, USA; Department of Biostatistics, Harvard School of Public Health; Department of Medicine, Harvard Medical School, Boston, USA. 5. Department of Breast Cancer Research, Institute of Cancer Biology, Danish Cancer Society, Copenhagen, Denmark. 6. International Breast Cancer Study Group Statistical Center, Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, USA; Department of Biostatistics, Harvard School of Public Health; Department of Medicine, Harvard Medical School, Boston, USA; International Breast Cancer Study Group Statistical Center, Frontier Science and Technology Research Foundation, Boston, USA. 7. International Breast Cancer Study Group Statistical Center, Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, USA; International Breast Cancer Study Group Statistical Center, Frontier Science and Technology Research Foundation, Boston, USA. 8. Department of Pathology, Herlev Hospital, Copenhagen University Hospital, Herlev, Denmark. 9. Division of Pathology and Laboratory Medicine, International Breast Cancer Study Group Pathology Review Office, European Institute of Oncology, University of Milan, Milan, Italy. 10. Danish Breast Cancer Cooperative Group Statistical Center; Department of Oncology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
Abstract
BACKGROUND:Estrogen Receptor 1 (ESR1) aberrations may be associated with expression of estrogen receptor (ER) or progesterone receptor (PgR), human epidermal growth factor receptor-2 (HER2) or Ki-67 labeling index and prognosis. PATIENTS AND METHODS: ESR1 was assessed in 1129 (81%) of 1396 postmenopausal Danish women with early breast cancer randomly assigned to receive 5 years of letrozole, tamoxifen or a sequence of these agents in the Breast International Group 1-98 trial and who had ER ≥ 1% after central review. RESULTS: By FISH, 13.6% of patients had an ESR1-to-Centromere-6 (CEN-6) ratio ≥ 2 (amplified), and 4.2% had ESR1-to-CEN-6 ratio <0.8 (deleted). Deletion of ESR1 was associated with significantly lower levels of ER (P < 0.0001) and PgR (P = 0.02) and more frequent HER2 amplification. ESR1 deletion or amplification was associated with higher-Ki-67 than ESR1-normal tumors. Overall, there was no evidence of heterogeneity of disease-free survival (DFS) or in treatment effect according to ESR1 status. However, significant differences in DFS were observed for subsets based on a combination of ESR1 and HER2 status (P = 0.02). CONCLUSIONS:ESR1 aberrations were associated with HER2 status, Ki-67 labeling index and ER and PgR levels. When combined with HER2, ESR1 may be prognostic but should not be used for endocrine treatment selection in postmenopausal women with endocrine-responsive early breast cancer.
RCT Entities:
BACKGROUND:Estrogen Receptor 1 (ESR1) aberrations may be associated with expression of estrogen receptor (ER) or progesterone receptor (PgR), human epidermal growth factor receptor-2 (HER2) or Ki-67 labeling index and prognosis. PATIENTS AND METHODS: ESR1 was assessed in 1129 (81%) of 1396 postmenopausal Danish women with early breast cancer randomly assigned to receive 5 years of letrozole, tamoxifen or a sequence of these agents in the Breast International Group 1-98 trial and who had ER ≥ 1% after central review. RESULTS: By FISH, 13.6% of patients had an ESR1-to-Centromere-6 (CEN-6) ratio ≥ 2 (amplified), and 4.2% had ESR1-to-CEN-6 ratio <0.8 (deleted). Deletion of ESR1 was associated with significantly lower levels of ER (P < 0.0001) and PgR (P = 0.02) and more frequent HER2 amplification. ESR1 deletion or amplification was associated with higher-Ki-67 than ESR1-normal tumors. Overall, there was no evidence of heterogeneity of disease-free survival (DFS) or in treatment effect according to ESR1 status. However, significant differences in DFS were observed for subsets based on a combination of ESR1 and HER2 status (P = 0.02). CONCLUSIONS:ESR1 aberrations were associated with HER2 status, Ki-67 labeling index and ER and PgR levels. When combined with HER2, ESR1 may be prognostic but should not be used for endocrine treatment selection in postmenopausal women with endocrine-responsive early breast cancer.
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