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Breast Cancer Research and Treatment

, Volume 143, Issue 2, pp 403–409 | Cite as

Estrogen receptor (ER) mRNA expression and molecular subtype distribution in ER-negative/progesterone receptor-positive breast cancers

  • Mitsuya Itoh
  • Takayuki Iwamoto
  • Junji Matsuoka
  • Tomohiro Nogami
  • Takayuki Motoki
  • Tadahiko Shien
  • Naruto Taira
  • Naoki Niikura
  • Naoki Hayashi
  • Shoichiro Ohtani
  • Kenji Higaki
  • Toshiyoshi Fujiwara
  • Hiroyoshi Doihara
  • W. Fraser Symmans
  • Lajos Pusztai
Brief Report

Abstract

We examined estrogen receptor (ER) mRNA expression and molecular subtypes in stage I–III breast cancers that are progesterone receptor (PR) positive but ER and HER2 negative by immunohistochemistry (IHC) or fluorescent in situ hybridization. The ER, PR, and HER2 status was determined by IHC as part of routine clinical assessment (N = 501). Gene expression profiling was done with the Affymetrix U133A gene chip. We compared expressions of ESR1 and MKI67 mRNA, distribution of molecular subtypes by the PAM50 classifier, the sensitivity to endocrine therapy index, and the DLDA30 chemotherapy response predictor signature among ER/PR-positive (n = 223), ER-positive/PR-negative (n = 73), ER-negative/PR-positive (n = 20), and triple-negative (n = 185) cancers. All patients received neoadjuvant chemotherapy with an anthracycline and taxane and had adjuvant endocrine therapy only if ER or PR > 10 % positive. ESR1 expression was high in 25 % of ER-negative/PR-positive, in 79 % of ER-positive/PR-negative, in 96 % of ER/PR-positive, and in 12 % of triple-negative cancers by IHC. The average MKI67 expression was significantly higher in the ER-negative/PR-positive and triple-negative cohorts. Among the ER-negative/PR-positive patients, 15 % were luminal A, 5 % were Luminal B, and 65 % were basal like. The relapse-free survival rate of ER-negative/PR-positive patients was equivalent to ER-positive cancers and better than the triple-negative cohort. Only 20–25 % of the ER-negative/PR-positive tumors show molecular features of ER-positive cancers. In this rare subset of patients (i) a second RNA-based assessment may help identifying the minority of ESR1 mRNA-positive, luminal-type cancers and (ii) the safest clinical approach may be to consider both adjuvant endocrine and chemotherapy.

Keywords

Estrogen receptor Progesteron receptor cDNA microarray Breast cancer Hormone therapy 

Abbreviations

ER

Estrogens receptor

PR

Progesterone receptor

IHC

Immunohistochemistry

HR

Hormone receptor

HER2

Human epidermal growth factor receptor 2

DLDA

Diagonal linear discriminant analysis

SET

Sensitivity to endocrine therapy

Notes

Acknowledgments

This work was supported by JSPS KAKENHI Grant Number: 25830101.

Disclosures

None.

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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Mitsuya Itoh
    • 1
    • 4
  • Takayuki Iwamoto
    • 1
  • Junji Matsuoka
    • 1
  • Tomohiro Nogami
    • 1
  • Takayuki Motoki
    • 1
  • Tadahiko Shien
    • 1
  • Naruto Taira
    • 1
  • Naoki Niikura
    • 2
  • Naoki Hayashi
    • 3
  • Shoichiro Ohtani
    • 4
  • Kenji Higaki
    • 4
  • Toshiyoshi Fujiwara
    • 1
  • Hiroyoshi Doihara
    • 1
  • W. Fraser Symmans
    • 5
  • Lajos Pusztai
    • 6
  1. 1.Okayama UniversityOkayamaJapan
  2. 2.Tokai UniversityKanagawaJapan
  3. 3.St Luke’s International HospitalTokyoJapan
  4. 4.Hiroshima City HospitalHiroshimaJapan
  5. 5.The University of Texas MD Anderson Cancer CenterHoustonUSA
  6. 6.Yale University Cancer CenterNew HavenUSA

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