Abstract
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 (∼30%) of early stage estrogen receptor–positive breast cancer patients with very poor outcome despite endocrine therapy.
- hoxb13:il17br
- molecular grade index
- prognosis
Footnotes
↵7 Z. Wang, D. Sgroi, unpublished data.
↵8 X. Ma, M. Erlander, D. Sgroi, unpublished data.
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Grant support: National Cancer Institute grant RO1-1CA112021-01 (D.C. Sgroi), the Department of Defense grant W81XWH-04-1-0606 (D.C. Sgroi), the Susan G. Komen Breast Cancer Foundation grant BCTR0402932 (D.C. Sgroi), a grant from the Avon Foundation (D.C. Sgroi) and the NCI SPORE in breast cancer at Massachusetts General Hospital (D.C. Sgroi).
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The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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Note: Supplementary data for this article are available at Clinical Cancer Research Online (http://clincancerres.aacrjournals.org/).
- Accepted January 17, 2008.
- Received November 30, 2007.
- Revision received January 17, 2008.
Volume 14, Issue 9
