The pharmacology and clinical uses of tamoxifen

Furr, B. J. A.; Jordan, V. Craig

doi:10.1016/0163-7258(84)90043-3

Cited by 845 publications

(389 citation statements)

References 301 publications

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“…The relative binding affinities of the four compounds for the oestrogen receptor in MCF-7 cells or rat uterus (Coezy et al, 1982;Furr & Jordan, 1984;Roos et al, 1983) agree well with the doses at which they inhibit oestrogen-induced growth. For instance at 10-6M, 4-hydroxytamoxifen completely blocked the effect of oestrogen, 3-hydroxytamoxifen reduced it by 75%, tamoxifen by 25%, and Ndesmethyltamoxifen was ineffective.…”

Section: Discussionsupporting

confidence: 61%

“…The growth stimulation of the MCF-7 cells by metabolite E was near maximal at 10 -9 M. This is a lower concentration than would have been predicted from its relative binding affinity for the rat uterine oestrogen receptor (Furr & Jordan, 1984) and suggests that the affinity of metabolite E for the human oestrogen receptor may be higher than reported. Different concentrations of metabolite E had no effect on the cell proliferation induced by a maximally stimulating concentration of oestradiol (2 x O-1OM).…”

Section: Discussionmentioning

confidence: 55%

“…Tamoxifen is the most frequently used endocrine therapy for post-menopausal women (Furr & Jordan, 1984). Remission is obtained in a third of all patients and in 50% of patients whose tumours contain oestrogen receptors.…”

mentioning

confidence: 99%

“…However, many patients do not respond and among those that do, the average time to relapse is only 14 months. Although tamoxifen is thought to act through the oestrogen receptor, its mechanism of action is not fully understood (Furr & Jordan, 1984).…”

mentioning

confidence: 99%

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Oestrogenic activity of tamoxifen and its metabolites on gene regulation and cell proliferation in MCF-7 breast cancer cells

Johnson

Westley²,

May³

1989

Br J Cancer

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Summary The effects of tamoxifen, three of its in vivo metabolites and 3-hydroxytamoxifen on cellular proliferation and the induction of four oestrogen-regulated RNAs (pNR-1, pNR-2, pNR-25 and cathepsin D) have been measured in MCF-7 breast cancer cells in phenol red-free culture medium. Tamoxifen and 3-hydroxytamoxifen acted as partial oestrogens to stimulate cell growth and the levels of the pNR-2 and pNR-25 RNAs. They were full oestrogens for the induction of cathepsin D RNA and induced the pNR-l RNA above the level found in oestrogen-treated cells. N-Desmethyltamoxifen and 4-hydroxytamoxifen behaved like tamoxifen except that N-desmethyltamoxifen did not induce the pNR-2 RNA and was only a partial oestrogen for the induction of cathepsin D RNA, and 4-hydroxytamoxifen did not induce the pNR-2 or pNR-25 RNAs. In the presence of oestradiol, the four anti-oestrogens prevented the stimulation of growth and reduced (pNR-2 and pNR-25) or increased (pNR-1) the RNA levels to those present in MCF-7 cells treated with the anti-oestrogen alone. In contrast, for cathepsin D RNA levels there was a synergistic effect of the anti-oestrogens and oestradiol. The concentration at which each anti-oestrogen was effective was related to its affinity for the oestrogen receptor. Metabolite E was a full oestrogen for the induction of cell proliferation and the oestrogen-regulated RNAs. pNR-25 and pNR-2 RNA levels correlated most closely with effects on cell proliferation. These RNAs are therefore potentially the most useful for predicting the response of breast cancer patients to tamoxifen therapy.

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Section: Discussionsupporting

confidence: 61%

Section: Discussionmentioning

confidence: 55%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Oestrogenic activity of tamoxifen and its metabolites on gene regulation and cell proliferation in MCF-7 breast cancer cells

Johnson

Westley²,

May³

1989

Br J Cancer

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“…The effects of tamoxifen on the human body vary and can be characterised as a mixture of oestrogenic and antioestrogenic properties, whereas exemestane inhibits in vivo aromatisation by about 98% and has no partial agonist activity, thus leading to a profound decrease in serum oestrogen levels (Furr and Jordan, 1984;Geisler et al, 1998). Two-thirds of breast tumours are oestrogen-dependent, and aromatase inhibitors can help block the growth of these tumours by lowering the amount of oestrogen in the body (Yeu and Santen, 1996).…”

Section: Discussionmentioning

confidence: 99%

Exemestane after tamoxifen as adjuvant hormonal therapy in postmenopausal women with breast cancer: effects on body composition and lipids

et al. 2006

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Recent studies have shown that administering the aromatase inhibitor exemestane after 2 -3 years of tamoxifen therapy significantly improves disease-free survival in postmenopausal women with primary breast cancer in comparison with standard 5-year tamoxifen treatment. Although many of the adverse effects associated with exemestane and tamoxifen have been analysed, there are no comparative data concerning body weight and body composition. The aim of this randomised study was to evaluate the longitudinal changes in body composition and lipid profiles in postmenopausal women switched from tamoxifen to exemestane. In total, 60 overweight or obese postmenopausal patients were enrolled. Their anthropometric data, body composition, including fat mass (FM) and fat-free mass (FFM), and lipid profiles, caloric intake and physical activity were assessed 1 week before randomisation, and 6 and 12 months later. In all, 55 patients (27 on tamoxifen and 28 on exemestane) completed the 1-year study period. Fat mass had significantly decreased by month 12 in the exemestane, but not in the tamoxifen group; the between-group difference was statistically significant (Po0.01). The FFM/FM ratio had significantly increased in the exemestane group, but not the tamoxifen group; the between-group difference was statistically significant (Po0.05). Triglycerides and high-density lipoprotein cholesterol significantly decreased (Po0.01; Po0.05), and low-density lipoprotein cholesterol significantly increased (Po0.01) in the exemestane group at the end of the 1-year study period. Our findings suggest that switching patients to adjuvant exemestane treatment after at least 2 years of tamoxifen therapy may be associated with an advantage over continuing adjuvant tamoxifen treatment in terms of body composition.

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The Mechanism of Hormone-Sensitive Breast Cancer Progression on Antiestrogen Therapy

et al. 1987

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The pharmacology and clinical uses of tamoxifen

Cited by 845 publications

References 301 publications

Oestrogenic activity of tamoxifen and its metabolites on gene regulation and cell proliferation in MCF-7 breast cancer cells

Oestrogenic activity of tamoxifen and its metabolites on gene regulation and cell proliferation in MCF-7 breast cancer cells

Exemestane after tamoxifen as adjuvant hormonal therapy in postmenopausal women with breast cancer: effects on body composition and lipids

The Mechanism of Hormone-Sensitive Breast Cancer Progression on Antiestrogen Therapy

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