Estrogen Receptor (ER) mRNA and ER-related gene expression in breast cancers that are 1% to 10% ER-positive by immunohistochemistry

Takayuki Iwamoto, Daniel Booser, Vicente Valero, James L. Murray, Kimberly Koenig, Francisco J. Esteva, Naoto T. Ueno, Jie Zhang, Weiwei Shi, Yuan Qi, Junji Matsuoka, Elliana J. Yang, Gabriel N. Hortobagyi, Christos Hatzis, W. Fraser Symmans, Lajos Pusztai

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201 Citations (Scopus)


Purpose: We examined borderline estrogen receptor (ER) -positive cancers, defined as having 1% to 10% positivity by immunohistochemistry (IHC), to determine whether they show the same global gene-expression pattern and high ESR1 mRNA expression as ER-positive cancers or if they are more similar to ER-negative cancers. Patients and Methods: ER status was determined by IHC in 465 primary breast cancers and with the Affymetrix U133A gene chip. We compared expressions of ESR1 mRNA and a 106 probe set ER-associated gene signature score between ER-negative (n = 183), 1% to 9% (n = 25), 10% (n = 6), and more than 10% (n = 251) ER-positive cancers. We also assessed the molecular class by using the PAM50 classifier and plotted survival by ER status. Results: Among the 1% to 9%, 10%, and more than 10% ER IHC-positive patients, 24%, 67%, and 92% were also positive by ESR1 mRNA expression. The average ESR1 expression was significantly higher in the ≥ 10% ER-positive cohorts compared with the 1% to 9% or ER-negative cohort. The average ER gene signature scores were similar for the ER-negative and 1% to 9% IHC-positive patients and were significantly lower than in ≥ 10% ER-positive patients. Among the 1% to 9% ER-positive patients, 8% were luminal B and 48% were basal-like; among the 10% ER-positive patients, 50% were luminal. The overall survival rate of 1% to 9% ER-positive patients with cancer was between those of patients in the ≥ 10% ER-positive and ER-negative groups. Conclusion: A minority of the 1% to 9% IHC ER-positive tumors show molecular features similar to those of ER-positive, potentially endocrine-sensitive tumors, whereas most show ER-negative, basal-like molecular characteristics. The safest clinical approach may be to use both adjuvant endocrine therapy and chemotherapy in this rare subset of patients.

Original languageEnglish
Pages (from-to)729-734
Number of pages6
JournalJournal of Clinical Oncology
Issue number7
Publication statusPublished - Mar 1 2012

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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