Effects of Tamoxifen on Bone Mineral Density in Postmenopausal Women With Breast Cancer

Love, Richard R.; Mazess, Richard B.; Barden, Howard S.; Epstein, Sol; Newcomb, Polly A.; Jordan, V. Craig; Carbone, Paul P.; DeMets, David L.

doi:10.1097/00006254-199208000-00024

Cited by 209 publications

(257 citation statements)

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“…In light of the partial agonistic activity, which reflects the complex regulation of oestrogen signalling in the body (Pennisi, 1996), tamoxifen treatment has also been associated with a reduction in coronary heart disease (Rutqvist et al, 1993;McDonald et al, 1995), prevention of bone density loss (Love et al, 1992), sporadic excess of venous thromboembolism (Fisher et al, 1989;McDonald et al, 1995) and endometrial cancer (Rutqvist et al, 1987;Fisher et al, 1994) in adjuvant clinical trials.…”

mentioning

confidence: 99%

Tamoxifen reduces plasma homocysteine levels in healthy women

Cattaneo

Baglietto²,

Zighetti³

et al. 1998

Br J Cancer

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Summary Treatment with tamoxifen is associated with reduced incidence of myocardial infarction. As plasma homocysteine is an independent risk factor for cardiovascular disease, we studied the effects of tamoxifen on plasma homocysteine in 66 healthy women participating in the Italian prevention trial of breast cancer who were randomized in a double-blind manner to tamoxifen 20 mg day-' or placebo for 5 years. They were aged between 35 and 70 years, had undergone previous hysterectomy for non-malignant conditions and had no cont(aindications to the use of tamoxifen. Plasma levels of total homocysteine (tHcy) were measured at randomization and after 2 and 6 months. The mean ± s.d. plasma levels of tHcy were 7.59 + 1.71 lmol 1-', 7.25 ± 1.61 and 7.09 + 1.33 in the tamoxifen group and 8.07 ± 2.06, 7.93 ± 1.77 and 8.12 + 2.04 in the placebo group at 0, 2 and 6 months (P= 0.008 for the between-group difference over time). The higher the baseline tHcy level, the greater was the lowering effect of tamoxifen. No statistically significant effect of age, body mass index or smoking habit on baseline tHcy levels and its variation over time was found. In conclusion, tamoxifen (20 mg day-' for 6 months) decreased plasma tHcy levels in healthy women. This effect may contribute to its protective effect on myocardial infarction.

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mentioning

confidence: 99%

Tamoxifen reduces plasma homocysteine levels in healthy women

Cattaneo

Baglietto²,

Zighetti³

et al. 1998

Br J Cancer

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“…Tamoxifen has oestrogen agonistic effects on bone and therefore prevents bone loss in postmenopausal women (Love et al, 1992;Ward et al, 1993;Kristensen et al, 1994;Powles et al, 1996). Tamoxifen has been shown to prevent bone loss predominantly in the lumbar spine (Love et al, 1992;Kristensen et al, 1994), but in two randomized studies this was also true for the upper femur (Ward et al, 1993;Powles et al, 1996).Toremifene is a close analogue to tamoxifen with demonstrated efficacy in advanced breast cancer (Valavaara et al, 1988). Compared with tamoxifen, toremifene is more oestrogen antagonistic than agonistic in rat (Di Salle et al, 1990).…”

mentioning

confidence: 99%

Clodronate improves bone mineral density in post-menopausal breast cancer patients treated with adjuvant antioestrogens

Saarto

Blomqvist²,

Välimäki³

et al. 1997

Br J Cancer

115

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Summary The effect of clodronate on bone mineral density (BMD) was studied in 121 post-menopausal breast cancer women without skeletal metastases. In addition, two antioestrogens, tamoxifen and toremifene, were compared in their action on bone mineral density. Patients were randomized to have an adjuvant antioestrogen treatment either 20 mg of tamoxifen or 60 mg of toremifene daily for 3 years. In addition all patients were randomized to have 1600 mg of oral clodronate daily or to act as control subjects. BMD of the lumbar spine and femoral neck were measured by dual-energy radiographic absorptiometry before therapy and at 1 and 2 years. At 2 years, clodronate with antioestrogens markedly increased BMD in the lumbar spine and femoral neck by 2.9% and 3.7% (P = 0.001 and 0.006 respectively). There were no significant changes in BMD in the patients given antioestrogens only. No significant differences were found between tamoxifen and toremifene on bone mineral density. Clodronate with antioestrogens significantly increased bone mass in the lumbar spine and femoral neck. Both antioestrogens, tamoxifen and toremifene, similarly prevented bone loss in the lumbar spine and femoral neck.Keywords: antioestrogens; bone mineral density; bisphosphonate; breast neoplasm; post-menopausal osteoporosis; toremifene Adjuvant antioestrogen treatment with tamoxifen significantly improves the survival of post-menopausal women with primary breast cancer (EBCTCG, 1992). Tamoxifen has oestrogen agonistic effects on bone and therefore prevents bone loss in postmenopausal women (Love et al, 1992;Ward et al, 1993;Kristensen et al, 1994;Powles et al, 1996). Tamoxifen has been shown to prevent bone loss predominantly in the lumbar spine (Love et al, 1992;Kristensen et al, 1994), but in two randomized studies this was also true for the upper femur (Ward et al, 1993;Powles et al, 1996).Toremifene is a close analogue to tamoxifen with demonstrated efficacy in advanced breast cancer (Valavaara et al, 1988). Compared with tamoxifen, toremifene is more oestrogen antagonistic than agonistic in rat (Di Salle et al, 1990). At present, no data are available on the effect of toremifene on bone.Since bisphosphonates prevent post-menopausal bone loss (Chesnut 1984; Reginster et al, 1989;Storm et al, 1990;Watts et al, 1990;Giannini et al, 1993;Harris et al, 1993;Reid et al, 1994;Filipponi et al, 1995;Liberman et al, 1995) and in advanced breast cancer reduced the development of new bone metastases (Elomaa et al, 1983;Martoni et al, 1991;Paterson et al, 1993;Van Holten Verzantvoort et al, 1993), they are attractive candidates for the treatment of patients with early breast cancer. We performed a prospective, open, randomized study to determine the effect of oral clodronate in post-menopausal women with primary breast cancer treated with adjuvant antioestrogens, Received 24 July 1996 Revised 10 October 1996 Accepted 15 October 1996 Correspondence to: Elomaa, Department of Oncology, Helsinki University Central Hospital, Haartmaninkatu 4, FIN-00290 Hels...

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“…The Wisconsin Tamoxifen Study was started in 1986 to explore the potential toxicity of tamoxifen on bone density. The study demonstrated, in a double blind placebo controlled clinical trial, that tamoxifen could preserve bone in the postmenopausal woman [110]. Bone building would clearly be an advantage for chemoprevention studies, thereby enhancing the possibility that the worth of tamoxifen to prevent breast cancer could be tested safely.…”

Section: Selective Estrogen Receptor Modulation and Chemopreventionmentioning

confidence: 93%

Development and evolution of therapies targeted to the estrogen receptor for the treatment and prevention of breast cancer

Jordan¹,

Brodie²

2007

Steroids

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The enthusiasm with which the clinical community has embraced the use of antiestrogenic therapy to treat breast cancer is based upon the proven record of success that first the nonsteroidal antiestrogen tamoxifen and then the aromatase inhibitor have demonstrated in clinical trial. The reasons for the enthusiasm are obvious. Antihormonal therapy, particularly aromatase inhibition to create a "no estrogen state" in the postmenopausal breast cancer patient is effective, saves women's lives, is contributing successfully to reducing the national mortality from breast cancer, is relatively cheap and has fewer side effects and easy administration (oral) than any other anticancer strategy. However, the successful application of a therapeutic strategy to block the known growth stimulation property of estrogen in breast cancer was not greeted with such enthusiasm 40 years ago.Estrogen is essential for life. Without the critical role of estrogenic steroids, reproduction would not be possible. Based on emerging knowledge from laboratory studies, the value of modulating the steroid environment during the menstrual cycle was advanced to clinical testing during the 1950's as a means of oral contraception. The results of these studies were to change society forever.The Worcester Foundation for Experimental Biology is the place where Gregory Pincus established the scientific principles necessary to propose clinical testing of the oral contraceptive and M.C. Chang subsequently established the first protocols to perform in vitro fertilization. Simply stated, the Worcester Foundation was, at that time, the world center for steroid endocrinology and reproductive biology. Over the years, hundreds of scientists have trained at the Foundation and subsequently spread their knowledge throughout the world [1]. However, fashions in research change and new opportunities emerge.In 1971, President Nixon made a national commitment to seek a cure for cancer by signing the National Cancer Act. Mahlon Hoagland, the President of the Worcester Foundation, responded to the initiative by appointing Professor Elwood V. Jensen, Director of the Ben May Cancer Research Laboratory at the University of Chicago, to be a member of the Foundation's Scientific Advisory Board. Jensen had discovered the estrogen receptor (ER) as the putative mechanism of estrogen action in its target tissues [2]. The known link between estrogen and breast cancer suggested that "antiestrogenic strategies" might have potential as therapeutic Correspondence to: V. Craig Jordan, v.craig.jordan@fccc.edu. Present Address: Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111-2497 Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be d...

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Effects of Tamoxifen on Bone Mineral Density in Postmenopausal Women With Breast Cancer

Cited by 209 publications

References 0 publications

Tamoxifen reduces plasma homocysteine levels in healthy women

Tamoxifen reduces plasma homocysteine levels in healthy women

Clodronate improves bone mineral density in post-menopausal breast cancer patients treated with adjuvant antioestrogens

Development and evolution of therapies targeted to the estrogen receptor for the treatment and prevention of breast cancer

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