Background: Osteogenic sarcoma (OS) is a bone tumor in which the malignant cells have many of the characteristics of bone. Estrogen is a strong modulator of bone metabolism, acting mainly through its nuclear receptors. The purpose of this study was to correlate estrogen receptor status and exposure to endogenous estrogen with outcome in patients with OS. Methods: 2107 osteogenic sarcoma patients registered in the Surveillance, Epidemiology, and End Results (SEER) program of the National Cancer Institute from 1973 to the present were analyzed. Patients were stratified into prepubertal, peripubertal, postpubertal, and mature groups. In addition, biopsy samples from the primary lesion of twenty-six patients with osteogenic sarcoma were assayed for expression of estrogen α and β receptors using reverse transcriptase polymerase chain reaction. The findings from these experiments were correlated with clinical data including patient age, sex, tumor location, size, histology, stage, development of metastasis, and event-free survival. Results: From the SEER database, peripubertal females had a significantly better prognosis than prepubertal females, peripubertal males, and postpubertal males. P-values were 0.03, 0.05, and 0.001, respectively. The incidence of osteogenic sarcoma was significantly lower in postpubertal females than in postpubertal males (p < 0.0003). There was no difference in incidence or prognosis between males and females before puberty. Analysis of OS patient samples revealed that estrogen receptor α expression was associated with event-free survival (p<0.023) and with absence of distant disease at presentation (p<0.035). Estrogen receptor β was not associated with any of the clinical parameters examined. Conclusion: Estrogen may exert a suppressive effect on OS in peripubertal females and may prevent tumorigenesis in postpubertal females. Expression of estrogen receptor α is associated with event-free survival and with localized disease at presentation. These findings suggest a potential role for estrogen metabolites in the treatment of osteogenic sarcoma.

[Proc Amer Assoc Cancer Res, Volume 46, 2005]