Type of estrogen receptor determines response to antiestrogen therapy.
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 wild-type 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.
Villa
E
E
Department of Internal Medicine, University of Modena, Italy.
Dugani
A
A
Fantoni
E
E
Camellini
L
L
Buttafoco
P
P
Grottola
A
A
Pompei
G
G
De Santis
M
M
Ferrari
A
A
Manenti
F
F
D000328:Adult; D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism / Q000648:ultrastructure*; D002455:Cell Division / Q000187:drug effects; D004965:Estrogen Antagonists / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000648:ultrastructure*; D008297:Male; D008535:Megestrol / Q000627:therapeutic use*; D008875:Middle Aged; D010865:Pilot Projects; D011960:Receptors, Estrogen / Q000145:classification / Q000378:metabolism / Q000502:physiology*; D013629:Tamoxifen / Q000627:therapeutic use*
D018931:Antineoplastic Agents, Hormonal; D004965:Estrogen Antagonists; D011960:Receptors, Estrogen; D013629:Tamoxifen; D008535:Megestrol