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- Jerevall, Piiha-Lotta, et al.
(författare)
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Exploring the two-gene ratio in breast cancer – independent roles for HOXB13 and IL17BR in prediction of clinical outcome
- 2008
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Ingår i: Breast Cancer Research and Treatment. - : Institutionen för klinisk och experimentell medicin. - 0167-6806 .- 1573-7217. ; 107:2, s. 225-234
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Tidskriftsartikel (refereegranskat)abstract
- Background: The two-gene expression ratio HOXB13:IL17BR has been proposed to predict the outcome of tamoxifen-treated breast cancer patients. We intended to examine whether this ratio can predict the benefit of 5 years vs. 2 years of tamoxifen treatment of postmenopausal patients. A further objective was to investigate any prognostic effects of the ratio in systemically untreated premenopausal patients. Based on the current knowledge of HOXB13 and IL17BR, we hypothesized that these genes may have individual prognostic or predictive power. Patients and methods: Expression of HOXB13 and IL17BR were quantified by real-time PCR in tumors from 264 randomized postmenopausal patients and 93 systemically untreated premenopausal patients. Results: A high HOXB13:IL17BR ratio was associated with aggressive tumor characteristics, as were low levels of IL17BR alone. The ratio and HOXB13 alone predicted recurrence-free survival after endocrine treatment, with a benefit of prolonged treatment in estrogen receptor-positive patients correlated to a low ratio (recurrence rate ratio: RR=0.39; p=0.030), or low expression of HOXB13 (RR=0.37; p=0.015). No difference in recurrence-free survival was seen for the high ratio or high HOXB13 subgroups. The predictive value of HOXB13 and HOXB13:IL17BR was significant in multivariate analysis. In the systemically untreated cohort, only IL17BR showed independent prognostic significance. Conclusion: We conclude that the ratio or HOXB13 alone can predict the benefit of endocrine therapy, with a high ratio or a high expression rendering patients less likely to respond. We have also shown that IL17BR might be an independent prognostic factor in breast cancer.
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| 2. |
- Niméus, Emma, et al.
(författare)
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Gene expression profiling in primary breast cancer distinguishes patients developing local recurrence after breast-conservation surgery, with or without postoperative radiotherapy
- 2008
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Ingår i: Breast Cancer Research. - : Springer Science and Business Media LLC. - 1465-5411 .- 1465-542X. ; 10:2
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Tidskriftsartikel (refereegranskat)abstract
- IntroductionSome patients with breast cancer develop local recurrence after breast-conservation surgery despite postoperative radiotherapy, whereas others remain free of local recurrence even in the absence of radiotherapy. As clinical parameters are insufficient for identifying these two groups of patients, we investigated whether gene expression profiling would add further information.MethodsWe performed gene expression analysis (oligonucleotide arrays, 26,824 reporters) on 143 patients with lymph node-negative disease and tumor-free margins. A support vector machine was employed to build classifiers using leave-one-out cross-validation.ResultsWithin the estrogen receptor-positive (ER+) subgroup, the gene expression profile clearly distinguished patients with local recurrence after radiotherapy (n = 20) from those without local recurrence (n = 80 with or without radiotherapy). The receiver operating characteristic (ROC) area was 0.91, and 5,237 of 26,824 reporters had a P value of less than 0.001 (false discovery rate = 0.005). This gene expression profile provides substantially added value to conventional clinical markers (for example, age, histological grade, and tumor size) in predicting local recurrence despite radiotherapy. Within the ER- subgroup, a weaker, but still significant, signal was found (ROC area = 0.74). The ROC area for distinguishing patients who develop local recurrence from those who remain local recurrence-free in the absence of radiotherapy was 0.66 (combined ER+/ER-).ConclusionA highly distinct gene expression profile for patients developing local recurrence after breast-conservation surgery despite radiotherapy has been identified. If verified in further studies, this profile might be a most important tool in the decision making for surgery and adjuvant therapy.
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