Selective estrogen receptor modulators (SERMS) and their roles in breast cancer prevention

Park, Woo Chan; Jordan, V. Craig

doi:10.1016/s1471-4914(02)02282-7

Cited by 122 publications

(72 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Unlike tamoxifen, raloxifene displays antiestrogenic effects on the endometrium and may serve as a safer alternative to tamoxifen in prevention [116]. A randomized placebo-controlled trial with 3 years of raloxifene treatment was conducted to demonstrate that this SERM efficiently prevents osteoporosis in postmenopausal women.…”

Section: Raloxifene and Tamoxifen Comparisonmentioning

confidence: 99%

Estrogens and their receptors in breast cancer progression: a dual role in cancer proliferation and invasion

Platet

Cathiard

Gleizes

et al. 2004

Critical Reviews in Oncology/Hematology

318

236

View full text Add to dashboard Cite

Estrogens play an important role in regulating the growth and differentiation of normal, premalignant and malignant cell types, especially breast epithelial cells, through interaction with two nuclear estrogen receptors (ER and ERIn this review, we present a brief overview of the actions of estrogens in the different steps of breast carcinogenesis, including cancer progression to metastasis, and of their clinical consequences in the prevention, prognosis and treatment of the disease. The requirement of estrogen receptors, mainly of the alpha subtype, in normal mammary gland differentiation and growth has been evidenced by estrogen receptor deficiency in animals. The promotion of breast cancer carcinogenesis by prolonged exposure to estrogens is well-documented and this has logically led to the use of antiestrogens as potentially chemopreventive agents. In breast cancer progression, however, the exact roles of estrogen receptors have been less well established but they may possibly be dual. Estrogens are mitogenic in ER-positive cells and antiestrogens are an efficient adjuvant therapy for these tumors. On the other hand, the fact that estrogens and their receptors protect against cancer cell invasiveness through distinct mechanisms in experimental models may explain why the presence of ER is associated with well-differentiated and less invasive tumors.2

show abstract

Section: Raloxifene and Tamoxifen Comparisonmentioning

confidence: 99%

Estrogens and their receptors in breast cancer progression: a dual role in cancer proliferation and invasion

Platet

Cathiard

Gleizes

et al. 2004

Critical Reviews in Oncology/Hematology

318

236

View full text Add to dashboard Cite

show abstract

“…The drug is also used for breast cancer prevention in high-risk subjects (2). Although two trials have shown that the nonsteroidal aromatase inhibitors anastrozole and letrozole may be superior to tamoxifen in the treatment of breast cancer of postmenopausal women (3,4), the long-term safety of these agents is unknown with possible detrimental effects at bone metabolism and cognitive disorders due to chronic estrogen deprivation in the brain tissue (5,6).…”

Section: Introductionmentioning

confidence: 99%

Tamoxifen and Metabolite Concentrations in Serum and Breast Cancer Tissue during Three Dose Regimens in a Randomized Preoperative Trial

Kisanga

Gjerde

Guerrieri-Gonzaga

et al. 2004

Clinical Cancer Research

181

124

View full text Add to dashboard Cite

Purpose: Both therapeutic and adverse effects of tamoxifen may be related to its tissue concentrations. We investigated concentrations of tamoxifen, 4-hydroxytamoxifen, Ndesmethyltamoxifen, and N-didesmethyltamoxifen in serum, normal breast, and breast cancer tissues during conventional dosage and two low-dose regimens. Furthermore we studied tamoxifen effects on the cancer proliferation marker Ki-67, and on sex hormone-binding globulin (SHBG).Experimental Design: From September 1999 to August 2001, 120 breast cancer patients were randomized to 20-, 5-, or 1-mg tamoxifen daily. We measured serum and tissue concentrations of tamoxifen and three metabolites after 28 days of treatment, and the changes between baseline and post-treatment levels of SHBG and Ki-67.Results: The median (range) tamoxifen concentrations (ng/ml) at doses of 1, 5, and 20 mg daily (n ‫؍‬ 38, 37, and 36) were 7.5 (2.9 -120.9), 25.2 (1.9 -180.9), and 83.6 (8.7-134.4) in serum, and 78.2 (35.9 -184), 272.3 (122-641), and 744.4 (208.6 -2556) in breast cancer tissue, respectively. Tamoxifen levels followed a dose-concentration relationship. The concentrations of tamoxifen and metabolites were related to each other. Serum and tissue concentrations of tamoxifen were associated with corresponding changes of SHBG levels, whereas changes of Ki-67 levels were not related. Conclusions:Estrogen agonistic effects of tamoxifen on SHBG decreased with lower dosage, whereas tamoxifen effects on Ki-67 expression did not change. This together with a >10-fold variation in serum tamoxifen concentrations and a serum to tissue concentration relationship suggest that tamoxifen treatment may be improved by administration of lower doses and therapeutic drug monitoring.

show abstract

“…Tamoxifen and other selective ER modulators (SERMs) exert their tissue-specific effects through interaction with one or both of the ERs (ER or ER ) (McDonnell et al 2002, Park & Jordan 2002. In the classical pathway for ER activation, ligand binding causes the receptors to undergo conformational changes and dimerise forming homo-or heterodimers, which bind to the palindromic oestrogen response element (ERE), leading to recruitment of coactivator proteins and transcription of oestrogen responsive genes (Edwards 2000, Klinge 2001).…”

Section: Introductionmentioning

confidence: 99%

Influence of oestradiol and tamoxifen on oestrogen receptors-α and -β protein degradation and non-genomic signalling pathways in uterine and breast carcinoma cells

Horner-Glister

Maleki-Dizaji²,

Guerin³

et al. 2005

Journal of Molecular Endocrinology

View full text Add to dashboard Cite

Tamoxifen acts as an oestrogen antagonist in the breast reducing cell proliferation, but in the uterus as an oestrogen agonist resulting in increased cell proliferation. Tamoxifen exerts its tissue-specific effects through the oestrogen receptors (ER or ER ). The levels and functions of the two ERs affect the response of the target tissue to oestrogen and tamoxifen. We examined the control of ER stability in breast and uterine cell lines using western blotting and RT-PCR. In MCF-7 breast-derived cells, ER and ER proteins were rapidly degraded via the proteasome pathway in response to oestradiol; conversely tamoxifen stabilised both receptors. In Ishikawa uterine-derived cells, oestradiol and tamoxifen stabilised ER but led to degradation of ER by the proteasome pathway. Further investigations showed that oestradiol induced activation of the non-genomic ER /Akt signalling pathway in MCF-7 cells. We have demonstrated that the alternative Erk signalling pathway is activated in Ishikawa cells following oestradiol treatment in the absence of an active proteasome pathway and therefore increased levels of ER . In conclusion, our data have demonstrated tamoxifen or oestradiol control of ER subtype stability and that non-genomic activation of transcription pathways is cell specific.

show abstract

Selective estrogen receptor modulators (SERMS) and their roles in breast cancer prevention

Cited by 122 publications

References 47 publications

Estrogens and their receptors in breast cancer progression: a dual role in cancer proliferation and invasion

Estrogens and their receptors in breast cancer progression: a dual role in cancer proliferation and invasion

Tamoxifen and Metabolite Concentrations in Serum and Breast Cancer Tissue during Three Dose Regimens in a Randomized Preoperative Trial

Influence of oestradiol and tamoxifen on oestrogen receptors-α and -β protein degradation and non-genomic signalling pathways in uterine and breast carcinoma cells

Contact Info

Product

Resources

About