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. 2012 Mar 1;30(7):729-34.
doi: 10.1200/JCO.2011.36.2574. Epub 2012 Jan 30.

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

Takayuki Iwamoto  1 , 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
Affiliations

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

Takayuki Iwamoto et al. J Clin Oncol. .

Abstract

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.

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