Prognostic Utility of HOXB13:IL17BR and Molecular Grade Index for Node-Negative Breast Cancer Patients.

Abstract

Abstract Background: Four studies have reported that a two-gene ratio (HOXB13:IL17BR) may be prognostic and/or predictive of tamoxifen benefit among early stage breast cancer patients. More recently, a 5-gene (BUB1B, CENPA, NEK2, RACGAP1, RRM2) molecular grade index (MGI) was reported to predict clinical outcome. We evaluated the performance of these two gene signatures among an independent population of lymph node-negative breast cancer patients from a community hospital setting.Methods: A case-control study was conducted among 4,964 Kaiser Permanente patients diagnosed with node-negative invasive breast cancer from 1985-94 and not treated with adjuvant chemotherapy (Habel, 2006). Archived tumor tissues were available on 169 cases (breast cancer deaths) and 335 matched controls and, using RT-PCR, were analyzed for expression levels of the above 7 cancer-related genes and 4 reference genes. Logistic regression methods were used to estimate the 10-year risk and the relative risk (RR) of breast cancer death associated with pre-specified risk categories based on cross-classification of HOXB13:IL17BR and MGI scores.Results: Approximately 50% of patients were classified as low risk by the HOXB13:IL17BR+MGI risk classifier. At 10 years, the risks of breast cancer death for ER+, tamoxifen-treated patients were 3.9% (95% confidence interval (CI) 2.2% - 5.5%), 5.6% (95% CI 2.6% - 8.5%), and 15.6% (95% CI 8.7% - 21.9%) for those in the low, intermediate and high risk groups, respectively. They were 5.9% (95% CI 4.2% - 7.5%), 15.2% (95% CI 8.3% - 21.5%), and 16.5% (95% CI 10.4% - 22.2%) for ER+ patients not treated with tamoxifen. After adjusting for tumor size and grade, the RRs of breast cancer death associated with high vs. low HOXB13:IL17BR+MGI risk categories were attenuated but remained elevated in both treatment groups; the RR continued to be statistically significant in tamoxifen treated patients only.Conclusion: In this population of lymph-node negative patients not treated with adjuvant chemotherapy, the HOXB13:IL17BR+MGI risk classifier was predictive of risk of breast cancer death and appeared to provide risk information beyond standard prognostic factors. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4034.