PMID- 21986093 OWN - NLM STAT- MEDLINE DCOM- 20120907 LR - 20240229 IS - 1569-8041 (Electronic) IS - 0923-7534 (Print) IS - 0923-7534 (Linking) VI - 23 IP - 5 DP - 2012 May TI - Prognostic and predictive role of ESR1 status for postmenopausal patients with endocrine-responsive early breast cancer in the Danish cohort of the BIG 1-98 trial. PG - 1138-1144 LID - S0923-7534(19)34698-8 [pii] LID - 10.1093/annonc/mdr438 [doi] AB - 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. FAU - Ejlertsen, B AU - Ejlertsen B AD - Danish Breast Cancer Cooperative Group Statistical Center; Department of Oncology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. Electronic address: ejlertsen@rh.dk. FAU - Aldridge, J AU - Aldridge J AD - International Breast Cancer Study Group Statistical Center, Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, USA. FAU - Nielsen, K V AU - Nielsen KV AD - Dako A/S, Glostrup, Denmark. FAU - Regan, M M AU - Regan MM AD - 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. FAU - Henriksen, K L AU - Henriksen KL AD - Department of Breast Cancer Research, Institute of Cancer Biology, Danish Cancer Society, Copenhagen, Denmark. FAU - Lykkesfeldt, A E AU - Lykkesfeldt AE AD - Department of Breast Cancer Research, Institute of Cancer Biology, Danish Cancer Society, Copenhagen, Denmark. FAU - Muller, S AU - Muller S AD - Dako A/S, Glostrup, Denmark. FAU - Gelber, R D AU - Gelber RD AD - 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. FAU - Price, K N AU - Price KN AD - 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. FAU - Rasmussen, B B AU - Rasmussen BB AD - Department of Pathology, Herlev Hospital, Copenhagen University Hospital, Herlev, Denmark. FAU - Viale, G AU - Viale G AD - Division of Pathology and Laboratory Medicine, International Breast Cancer Study Group Pathology Review Office, European Institute of Oncology, University of Milan, Milan, Italy. FAU - Mouridsen, H AU - Mouridsen H AD - Danish Breast Cancer Cooperative Group Statistical Center; Department of Oncology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. CN - Danish Breast Cancer Cooperative Group the BIG 1-98 Collaborative Group and the International Breast Cancer Study Group LA - eng GR - U24 CA075362/CA/NCI NIH HHS/United States GR - CA-75362/CA/NCI NIH HHS/United States PT - Evaluation Study PT - Journal Article PT - Multicenter Study PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20111010 PL - England TA - Ann Oncol JT - Annals of oncology : official journal of the European Society for Medical Oncology JID - 9007735 RN - 0 (Antineoplastic Agents, Hormonal) RN - 0 (Biomarkers, Tumor) RN - 0 (ESR1 protein, human) RN - 0 (Estrogen Receptor alpha) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Antineoplastic Agents, Hormonal/*therapeutic use MH - Biomarkers, Tumor/analysis/metabolism/physiology MH - Breast Neoplasms/*diagnosis/*drug therapy/metabolism/pathology MH - Carcinoma/*diagnosis/*drug therapy/metabolism/pathology MH - Cohort Studies MH - Denmark MH - Estrogen Receptor alpha/analysis/metabolism/*physiology MH - Female MH - Humans MH - Middle Aged MH - Neoplasm Staging MH - Postmenopause/genetics/metabolism MH - Predictive Value of Tests MH - Prognosis MH - Randomized Controlled Trials as Topic MH - Treatment Outcome PMC - PMC3335246 EDAT- 2011/10/12 06:00 MHDA- 2012/09/08 06:00 PMCR- 2013/05/01 CRDT- 2011/10/12 06:00 PHST- 2011/10/12 06:00 [entrez] PHST- 2011/10/12 06:00 [pubmed] PHST- 2012/09/08 06:00 [medline] PHST- 2013/05/01 00:00 [pmc-release] AID - S0923-7534(19)34698-8 [pii] AID - 10.1093/annonc/mdr438 [doi] PST - ppublish SO - Ann Oncol. 2012 May;23(5):1138-1144. doi: 10.1093/annonc/mdr438. Epub 2011 Oct 10.