Failure of tamoxifen treatment for unresectable hepatocellular carcinomas (HCCs) might be caused by variant estrogen receptors (ERs) in some of these tumors. We therefore planned a study in which antihormonal therapy was done with 80 mg/day tamoxifen or 160 mg/day megestrol according to the presence of wild-type or exon 5-deleted variant ER transcripts.

Growth rate (evaluated by MRI) of HCCs characterized by variant ER transcripts was 4 times more rapid than that of HCCs with wild-type ERs. Tumor volume in all patients with wild-type ERs was halved after 9 months of tamoxifen treatment, whereas megestrol in patients with variant ERs only slowed down tumor growth.

Choosing antihormonal treatment according to the presence of wildtype or variant ERs in the tumor definitely improves the response rate to tamoxifen; in patients with tumors bearing variant ERs, megestrol causes only a temporary inhibition of tumor growth.

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This work was supported by grants from the University of Modena (60%) and from the Ministero dell'Università e Ricerca Scientifica (Progetto Cirrosi Epatica; 40%). A. D. is the recipient of a PhD fellowship from the Libyan Ministry of Higher Education. P. B. is the recipient of a training fellowship in Molecular Biology from the University of Modena.

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