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The association of mRNA expression levels of leptin receptors (long isoform: Lep-R(L) and short isoform: Lep-R(S)) in breast cancer tissue with patient prognosis was studied with special reference to the serum leptin level or theleptinmRNA level in tumor tissue.Lep-R(L), Lep-R(S) andleptinmRNA levels in breast cancer tissue (n= 91) were determined with a real-time PCR assay, and serum leptin levels in breast cancer patients (n= 67) with an enzyme-linked immunosorbent assay. NeitherLep-R(L) norLep-R(S) mRNA levels in tumor tissue were significantly associated with patient prognosis, but both intratumoralLep-R(L) andLep-R(S) mRNA high tumors were significantly (p< 0.01) associated with a poor prognosis. Multivariate analysis showed that a high level of bothLep-R (L) andLep-R (S) mRNA in tumor tissue was a significant risk factor, independent of other risk factors. The subset analysis demonstrated that both intratumoralLep-R(L) andLep-R(S) mRNA high tumors were significantly associated with a poor prognosis for the subset of patients with high serum leptin or high intratumoralleptinmRNA levels but not in the subset of patients with low serum leptin or low intratumoralleptinmRNA levels. The association between both intratumoralLep-R(L) andLep-R(S) mRNA high tumors and a poor prognosis in the presence of high serum leptin or high intratumoralleptinmRNA levels seems to suggest that the leptin andLep-R(L)/Lep-R(S) pathways are implicated in the growth stimulation of breast tumors. The well-established finding that obesity serves as a risk factor for relapse in breast cancer patients may thus be partially explained by the high serum leptin level seen in obese women.