title: 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.
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.
  
  
  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.
authors: Danish Breast Cancer Cooperative Group Statistical Center; Department of Oncology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. Electronic address: ejlertsen@rh.dk.
authors: B
authors: B
authors: Ejlertsen
authors: International Breast Cancer Study Group Statistical Center, Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, USA.
authors: J
authors: J
authors: Aldridge
authors: Dako A/S, Glostrup, Denmark.
authors: K V
authors: KV
authors: Nielsen
authors: 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.
authors: M M
authors: MM
authors: Regan
authors: Department of Breast Cancer Research, Institute of Cancer Biology, Danish Cancer Society, Copenhagen, Denmark.
authors: K L
authors: KL
authors: Henriksen
authors: Department of Breast Cancer Research, Institute of Cancer Biology, Danish Cancer Society, Copenhagen, Denmark.
authors: A E
authors: AE
authors: Lykkesfeldt
authors: Dako A/S, Glostrup, Denmark.
authors: S
authors: S
authors: Müller
authors: 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.
authors: R D
authors: RD
authors: Gelber
authors: 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.
authors: K N
authors: KN
authors: Price
authors: Department of Pathology, Herlev Hospital, Copenhagen University Hospital, Herlev, Denmark.
authors: B B
authors: BB
authors: Rasmussen
authors: Division of Pathology and Laboratory Medicine, International Breast Cancer Study Group Pathology Review Office, European Institute of Oncology, University of Milan, Milan, Italy.
authors: G
authors: G
authors: Viale
authors: Danish Breast Cancer Cooperative Group Statistical Center; Department of Oncology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
authors: H
authors: H
authors: Mouridsen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis / Q000378:metabolism / Q000502:physiology; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002277:Carcinoma / Q000175:diagnosis* / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D015331:Cohort Studies; D003718:Denmark; D047628:Estrogen Receptor alpha / Q000032:analysis / Q000378:metabolism / Q000502:physiology*; D005260:Female; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D017698:Postmenopause / Q000235:genetics / Q000378:metabolism; D011237:Predictive Value of Tests; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome
chemical_list: D018931:Antineoplastic Agents, Hormonal; D014408:Biomarkers, Tumor; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha