A 3-gene proliferation score (TOP-FOX-67) can re-classify histological grade-2, ER-positive breast cancers into low- and high-risk prognostic categories

Borbala Szekely, Takayuki Iwamoto, A. Marcell Szasz, Yuan Qi, Junji Matsuoka, W. Fraser Symmans, Anna Maria Tokes, Janina Kulka, Charles Swanton, Lajos Pusztai

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

The goal of this study was to assess the prognostic value of a 3-gene (TOP2A, FOXM1, and MKI67) proliferation score and use it to risk stratify grade-2, estrogen receptor (ER)-positive breast cancers into low- and high-risk groups. We used 4 different breast cancer gene expression datasets including two cohorts of patients who received no systemic adjuvant therapy (Mainz: n = 206, TRANSBIG: n = 134) and two other cohorts that received adjuvant tamoxifen (JBI: n = 227, MDACC/SET: n = 192). We compared individual and combined expression values of the 3 genes between grade 1, 2, and 3 tumors and plotted distant metastasis-free survival (DMFS) curves by the 3-gene score for grade-2 cancers. We compared the prognostic value of the 3-gene score to the Genomic Grade Index (GGI). The individual and combined expression of TOP2A, FOXM1, and MKI67 were significantly different between the 3 histological grade groups with the highest expression in grade-3 and the lowest in grade-1 cancers. Expression levels were variable in grade-2 cancers. Grade-2 tumors with high expression of the 3 genes (>median) showed significantly worse DMFS in one prognostic and one tamoxifen-treated set and showed a similar but non-significant trend for worse survival in the remaining two datasets. The 3-gene score performed equally well in risk stratification as the GGI. A 3-gene proliferation score shows similar prognostic value as the GGI in ER-positive, grade-2 cancers and may serve as basis for a PCR-based assay that could aid prognostic prediction for clinically intermediate-risk cancers.

Original languageEnglish
Pages (from-to)691-698
Number of pages8
JournalBreast Cancer Research and Treatment
Volume138
Issue number3
DOIs
Publication statusPublished - Apr 2013

Fingerprint

Estrogen Receptors
Breast Neoplasms
Genes
Neoplasms
Tamoxifen
Survival
Neoplasm Metastasis
Gene Expression
Neoplasm Genes
Polymerase Chain Reaction

Keywords

  • Breast cancer
  • FOXM1
  • Genomic grade index
  • Histological Grade
  • MKI67
  • TOP2A

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

A 3-gene proliferation score (TOP-FOX-67) can re-classify histological grade-2, ER-positive breast cancers into low- and high-risk prognostic categories. / Szekely, Borbala; Iwamoto, Takayuki; Szasz, A. Marcell; Qi, Yuan; Matsuoka, Junji; Symmans, W. Fraser; Tokes, Anna Maria; Kulka, Janina; Swanton, Charles; Pusztai, Lajos.

In: Breast Cancer Research and Treatment, Vol. 138, No. 3, 04.2013, p. 691-698.

Research output: Contribution to journalArticle

Szekely, Borbala ; Iwamoto, Takayuki ; Szasz, A. Marcell ; Qi, Yuan ; Matsuoka, Junji ; Symmans, W. Fraser ; Tokes, Anna Maria ; Kulka, Janina ; Swanton, Charles ; Pusztai, Lajos. / A 3-gene proliferation score (TOP-FOX-67) can re-classify histological grade-2, ER-positive breast cancers into low- and high-risk prognostic categories. In: Breast Cancer Research and Treatment. 2013 ; Vol. 138, No. 3. pp. 691-698.
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abstract = "The goal of this study was to assess the prognostic value of a 3-gene (TOP2A, FOXM1, and MKI67) proliferation score and use it to risk stratify grade-2, estrogen receptor (ER)-positive breast cancers into low- and high-risk groups. We used 4 different breast cancer gene expression datasets including two cohorts of patients who received no systemic adjuvant therapy (Mainz: n = 206, TRANSBIG: n = 134) and two other cohorts that received adjuvant tamoxifen (JBI: n = 227, MDACC/SET: n = 192). We compared individual and combined expression values of the 3 genes between grade 1, 2, and 3 tumors and plotted distant metastasis-free survival (DMFS) curves by the 3-gene score for grade-2 cancers. We compared the prognostic value of the 3-gene score to the Genomic Grade Index (GGI). The individual and combined expression of TOP2A, FOXM1, and MKI67 were significantly different between the 3 histological grade groups with the highest expression in grade-3 and the lowest in grade-1 cancers. Expression levels were variable in grade-2 cancers. Grade-2 tumors with high expression of the 3 genes (>median) showed significantly worse DMFS in one prognostic and one tamoxifen-treated set and showed a similar but non-significant trend for worse survival in the remaining two datasets. The 3-gene score performed equally well in risk stratification as the GGI. A 3-gene proliferation score shows similar prognostic value as the GGI in ER-positive, grade-2 cancers and may serve as basis for a PCR-based assay that could aid prognostic prediction for clinically intermediate-risk cancers.",
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AU - Matsuoka, Junji

AU - Symmans, W. Fraser

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AU - Swanton, Charles

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