Tamoxifen as an Anti-Tumour Agent: Effect on Oestrogen Binding

Jordan, V. Craig; Dowse, L. J.

doi:10.1677/joe.0.0680297

Cited by 137 publications

(48 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In general there was no difference in the extent to which hormones were suppressed by these agents in responders and non-responders to therapy. Responders Similarly, the effect of tamoxifen on gonadotrophin concentrations is likely to be a secondary effect, since it is known that the major site of action of the drug is on RE (Jordan & Dowse, 1976). However, we have demonstrated that after tamoxifen therapy, the tumour is RE- (Taylor et al, in press), suggesting that tamoxifen is still capable of binding to RE on relapse or non-response.…”

Section: Discussionmentioning

confidence: 72%

Tamoxifen, aminoglutethimide and danazol: effect of therapy on hormones in post-menopausal patients with breast cancer

Coombes¹,

Powles²,

Rees³

et al. 1982

Br J Cancer

View full text Add to dashboard Cite

Summary.-Gonadotrophins, oestradiol, androstenedione, testosterone and dehydroepiandrosterone sulphate (DHAS) were measured sequentially in 72 patients with advanced breast cancer receiving endocrine therapy of various types. Tamoxifen significantly reduced gonadotrophins but did not effect other hormones. Danazol also reduced gonadotrophins. Aminoglutethimide (AGT) reduced oestradiol and DHAS but had no effect on gonadotrophins. The effects of administering tamoxifen, AGT and danazol together (TAD) together were therefore examined. This combination reduced gonadotrophins, oestradiol and DHAS, but no further than tamoxifen and AGT alone.The degree and duration of hormone suppression were similar in both responders and non-responders to tamoxifen, AGT or TAD, though patients responding to AGT showed more complete suppression at the end of the course of treatment, perhaps because they were treated longer. On relapse, adequate gonadotrophin and steroid suppression was demonstrated in patients receiving tamoxifen and AGT respectively.We conclude that (a) response to endocrine therapy is unlikely to be related to the degree of endocrine suppression produced by the therapy; (b) combination endocrine therapy does not further reduce serum-hormone concentrations and (c) relapse is unlikely to be due to escape from the hormone-inhibitory effects of endocrine agents.ENDOCRINE THERAPY is an effective form of treatment in patients with advanced breast cancer. However, only a proportion of patients respond, and their response is often transient. Patients whose tumours contain a high concentration of oestrogen receptor are more likely to respond to endocrine therapy (McGuire et al., 1975) but a moderate proportion of patients whose tumours contain receptor do not respond, and it may be that in these patients inadequate hormone suppression by endocrine therapy is responsible for lack of effect in these patients.Few studies have been carried out to elucidate the mechanism of relapse. It is not known whether endocrine therapy is still effective at the time of relapse, nor whether relapse is due to premature inactivation of endocrine agents. Studies from our unit have indicated that relapse is not often due to proliferation of an oestrogen-receptor negative (RE-) cell population, since most relapsing tumours * Priesent address:

show abstract

Section: Discussionmentioning

confidence: 72%

Tamoxifen, aminoglutethimide and danazol: effect of therapy on hormones in post-menopausal patients with breast cancer

Coombes¹,

Powles²,

Rees³

et al. 1982

Br J Cancer

View full text Add to dashboard Cite

show abstract

“…However, a strategic plan was developing to use tamoxifen in a broader range of patient populations. Laboratory studies conducted in the 1970's showed that tamoxifen blocked estrogen binding to the ER [15][16][17], should be used as a long-term adjuvant therapy to suppress tumor recurrence [18][19][20] and the drug also had potential as a chemopreventive agent [21,22].…”

Section: Tamoxifen the First Sermmentioning

confidence: 99%

New insights into the metabolism of tamoxifen and its role in the treatment and prevention of breast cancer

2007

View full text Add to dashboard Cite

The metabolism of tamoxifen is being redefined in the light of several important pharmacological observations. Recent studies have identified 4-hydroxy N-desmethyl tamoxifen (endoxifen) as an important metabolite of tamoxifen necessary for antitumor actions. The metabolite is formed through the enzymatic product of CYP2D6 which also interacts with specific selective serotonin reuptake inhibitors (SSRIs) used to prevent the hot flashes observed in up to 45% of patients taking tamoxifen. Additionally, the finding that enzyme variants of CYP2D6 do not promote the metabolism of tamoxifen to endoxifen means that significant numbers of women might not receive optimal benefit from tamoxifen treatment. Clearly these are particularly important issues not only for breast cancer treatment but also for selecting premenopausal women, at high risk for breast cancer, as candidates for chemoprevention using tamoxifen.

show abstract

“…The secondary hypothesis to be addressed was that only ER positive disease would respond as tamoxifen and metabolites blocked the binding of [ 3 H]-oestradiol to tumour ER [39,[68][69][70].…”

Section: Laboratory Modelmentioning

confidence: 99%

Proven value of translational research with appropriate animal models to advance breast cancer treatment and save lives: the tamoxifen tale

Jordan

2015

Brit J Clinical Pharma

View full text Add to dashboard Cite

Tamoxifen as an Anti-Tumour Agent: Effect on Oestrogen Binding

Cited by 137 publications

References 22 publications

Tamoxifen, aminoglutethimide and danazol: effect of therapy on hormones in post-menopausal patients with breast cancer

Tamoxifen, aminoglutethimide and danazol: effect of therapy on hormones in post-menopausal patients with breast cancer

New insights into the metabolism of tamoxifen and its role in the treatment and prevention of breast cancer

Proven value of translational research with appropriate animal models to advance breast cancer treatment and save lives: the tamoxifen tale

Contact Info

Product

Resources

About