Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

PURPOSE: Histologic tumor grade is a well-established prognostic factor for breast cancer, and tumor grade-associated genes are the common denominator of many prognostic gene signatures. The objectives of this study are as follows: (a) to develop a simple gene expression index for tumor grade (molecular grade index or MGI), and (b) to determine whether MGI and our previously described HOXB13:IL17BR index together provide improved prognostic information. EXPERIMENTAL DESIGN: From our previously published list of genes whose expression correlates with both tumor grade and tumor stage progression, we selected five cell cycle-related genes to build MGI and evaluated MGI in two publicly available microarray data sets totaling 410 patients. Using two additional cohorts (n = 323), we developed a real-time reverse transcription PCR assay for MGI, validated its prognostic utility, and examined its interaction with HOXB13:IL17BR. RESULTS: MGI performed consistently as a strong prognostic factor and was comparable with a more complex 97-gene genomic grade index in multiple data sets. In patients treated with endocrine therapy, MGI and HOXB13:IL17BR modified each other's prognostic performance. High MGI was associated with significantly worse outcome only in combination with high HOXB13:IL17BR, and likewise, high HOXB13:IL17BR was significantly associated with poor outcome only in combination with high MGI. CONCLUSIONS: We developed and validated a five-gene reverse transcription PCR assay for MGI suitable for analyzing routine formalin-fixed paraffin-embedded clinical samples. The combination of MGI and HOXB13:IL17BR outperforms either alone and identifies a subgroup ( approximately 30%) of early stage estrogen receptor-positive breast cancer patients with very poor outcome despite endocrine therapy.

Original publication

DOI

10.1158/1078-0432.CCR-07-5026

Type

Journal article

Journal

Clin cancer res

Publication Date

01/05/2008

Volume

14

Pages

2601 - 2608

Keywords

Autoantigens, Breast Neoplasms, Centromere Protein A, Chromosomal Proteins, Non-Histone, Cohort Studies, Gene Expression Profiling, Genes, Neoplasm, Homeodomain Proteins, Humans, Kaplan-Meier Estimate, NIMA-Related Kinases, Prognosis, Proportional Hazards Models, Protein-Serine-Threonine Kinases, Receptors, Interleukin, Ribonucleoside Diphosphate Reductase