Is human hepatocellular carcinoma a hormone-responsive tumor?
Before the positive results recently obtained with multitarget tyrosine kinase inhibitor sorafenib, there was no standard systemic treatment for patients with advanced hepatocellular carcinoma (HCC). Sex hormones receptors are expressed in a significant proportion of HCC samples. Following preclinical and epidemiological studies supporting a relationship between sex hormones and HCC tumorigenesis, several randomized controlled trials (RCTs) tested the efficacy of the anti-estrogen tamoxifen as systemic treatment. Largest among these trials showed no survival advantage from the administration of tamoxifen, and the recent Cochrane systematic review produced a completely negative result. This questions the relevance of estrogen receptor-mediated pathways in HCC. However, a possible explanation for these disappointing results is the lack of proper patients selection according to sex hormones receptors expression, but unfortunately the interaction between this expression and efficacy of tamoxifen has not been studied adequately. It has been also proposed that negative results might be explained if tamoxifen acts in HCC via an estrogen receptor-independent pathway, that requires higher doses than those usually administered, but an Asian RCT conducted to assess dose-response effect was completely negative. Interesting, preliminary results have been obtained when hormonal treatment (tamoxifen or megestrol) has been selected according to the presence of wild-type or variant estrogen receptors respectively, but no large RCTs are available to support this strategy. Negative results have been obtained also with anti-androgen therapy. In conclusion, there is no robust evidence to consider HCC a hormone-responsive tumor. Hormonal treatments should not be part of the current management of HCC.
Di Maio
Massimo
M
Medical Oncology, N.Giannettasio' Hospital, Rossano 87068, Italy.
Daniele
Bruno
B
Pignata
Sandro
S
Gallo
Ciro
C
De Maio
Ermelinda
E
Morabito
Alessandro
A
Piccirillo
Maria-Carmela
MC
Perrone
Francesco
F
D000726:Androgen Antagonists / Q000627:therapeutic use; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism; D019317:Evidence-Based Medicine; D012739:Gonadal Steroid Hormones / Q000378:metabolism; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D019290:Megestrol Acetate / Q000627:therapeutic use; D015201:Meta-Analysis as Topic; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy* / Q000378:metabolism; D018579:Patient Selection; D017410:Practice Guidelines as Topic; D016032:Randomized Controlled Trials as Topic; D011987:Receptors, Steroid / Q000378:metabolism; D020845:Selective Estrogen Receptor Modulators / Q000627:therapeutic use; D013629:Tamoxifen / Q000627:therapeutic use; D016896:Treatment Outcome
D000726:Androgen Antagonists; D018931:Antineoplastic Agents, Hormonal; D012739:Gonadal Steroid Hormones; D011987:Receptors, Steroid; D020845:Selective Estrogen Receptor Modulators; D013629:Tamoxifen; D019290:Megestrol Acetate