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In summary, our results suggest that HO-1 can decrease H/R-induced myocardiac cell apoptosis; the mechanism may be related to the activation of the Akt signaling pathway and, furthermore, to the inhibition of the JNK/c-Jun/caspase-3 signaling pathway.

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Background: A significant proportion of ER-positive tumors exhibit resistance to endocrine therapy. Clinical studies in LNN/ER+ patients show that the absolute distant disease-free survival benefit of tamoxifen therapy is only about 9%, with a relative benefit of about 30%. These benefits from treatment may, however, differ substantially according to e.g. patient's age and the tumor level of ER and it is therefore of importance to identify biomarkers that allow identification of those breast cancer patients who may actually benefit from adjuvant tamoxifen. This study was to assess the benefit from adjuvant systemic tamoxifen therapy in breast cancer risk groups identified by the previously established prognostic 76-gene signature.Material and Methods: In 300 lymph node-negative (LNN) estrogen receptor-positive (ER+) breast cancer patients (136 treated with adjuvant tamoxifen, 164 having received no systemic adjuvant therapy), distant metastasis-free survival (DMFS) as a function of the 76-gene signature was determined in a multicenter fashion.Results: In 136 tamoxifen-treated patients, the 76-gene signature identified a group of patients with a poor prognosis (hazard ratio (HR), 4.62, P = 0.0248). These patients showed a 12.3% absolute benefit of tamoxifen in 10-year DMFS (HR, 0.52, P = 0.0318) compared with untreated high-risk patients. This represented a 71% increase in relative benefit compared with the 7.2% absolute benefit observed for all 300 patients without using the gene signature. In the low-risk group there was no significant 10-year DMFS benefit of tamoxifen.Discussion: In summary, the 76-gene signature defines high-risk patients who benefit from adjuvant tamoxifen therapy. Although we did not study the value of chemotherapy in this study, low-risk patients identified by the 76-gene signature have a prognosis good enough that chemotherapy would be difficult to justify. The prognosis of these patients is sufficiently good, in fact, that a disease-free benefit for tamoxifen therapy is difficult to prove, though benefits in terms of oco-regional relapse and a reduction in risk for contralateral breast cancer might justify ormonal therapy in these patients. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 2021.