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

Ann Oncol. 2012 May;23(5):1138-1144. doi: 10.1093/annonc/mdr438. Epub 2011 Oct 10.

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.

Publication types

  • Evaluation Study
  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents, Hormonal / therapeutic use*
  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / metabolism
  • Biomarkers, Tumor / physiology
  • Breast Neoplasms / diagnosis*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Carcinoma / diagnosis*
  • Carcinoma / drug therapy*
  • Carcinoma / metabolism
  • Carcinoma / pathology
  • Cohort Studies
  • Denmark
  • Estrogen Receptor alpha / analysis
  • Estrogen Receptor alpha / metabolism
  • Estrogen Receptor alpha / physiology*
  • Female
  • Humans
  • Middle Aged
  • Neoplasm Staging
  • Postmenopause / genetics
  • Postmenopause / metabolism
  • Predictive Value of Tests
  • Prognosis
  • Randomized Controlled Trials as Topic
  • Treatment Outcome

Substances

  • Antineoplastic Agents, Hormonal
  • Biomarkers, Tumor
  • ESR1 protein, human
  • Estrogen Receptor alpha