Tamoxifen and bone metabolism in postmenopausal low-risk breast cancer patients: a randomized study.

Kristensen, Bent Bruun; Ejlertsen, Bent; Dalgaard, Peter; Larsen, Linda Hovanessian; Holmegaard, Stig Nistrup; Transbøl, Ib; Mouridsen, H. T.

doi:10.1200/jco.1994.12.5.992

Cited by 201 publications

(82 citation statements)

References 19 publications

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“…In line with prior investigations, post-menopausal breast cancer patients treated with antioestrogens did not lose bone at the lumbar spine or at the femoral neck (Love et al, 1992;Ward et al, 1993;Kristensen et al, 1994;Powles et al, 1996). Previous data on tamoxifen were extended by the finding that a novel antioestrogen, toremifene, preserved bone mass as effectively as tamoxifen, although experimental data havo shown it to be less oestrogenic than tamoxifen (Di Salle et al, 1990).…”

Section: Discussionsupporting

confidence: 61%

“…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).…”

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confidence: 99%

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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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Section: Discussionsupporting

confidence: 61%

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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“…The percentage change in hip and lumbar spine BMD for all patients in aggregate, as well as for patients divided by chemotherapy and/or menopausal status, is presented in Tables 3 and 4, respectively. The average change in T score between baseline and 12 months for patients divided by chemotherapy or menopausal status is given in Supplementary Table 1. Similar to previously reported results, postmenopausal women had an increase in BMD at the hip ( þ 0.8%) and stability of BMD at the lumbar spine (À0.1%) with 1 year of tamoxifen therapy (Love et al, 1992;Kristensen et al, 1994;Powles et al, 1996). Consistent with earlier reports, BMD decreased at both the hip (À0.5%) and lumbar spine (À2.4%) in premenopausal women (Powles et al, 1996;Sverrisdottir et al, 2004).…”

Section: Baseline Bmdsupporting

confidence: 81%

“…It has antagonistic effects on breast tissue, thereby inhibiting the growth of hormone-responsive tumours. Classically, tamoxifen has been considered to have oestrogenic effects on bone, and postmenopausal women typically experience an increase in BMD with tamoxifen therapy (Love et al, 1992;Kristensen et al, 1994;Powles et al, 1996). Conversely, tamoxifen therapy results in decreased BMD in premenopausal women, although the reason for this difference remains unclear (Powles et al, 1996;Sverrisdottir et al, 2004).…”

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confidence: 99%

Lack of association between oestrogen receptor polymorphisms and change in bone mineral density with tamoxifen therapy

et al. 2009

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BACKGROUND: Tamoxifen, a selective oestrogen receptor (ER) modulator, increases bone mineral density (BMD) in postmenopausal women and decreases BMD in premenopausal women. We hypothesised that inherited variants in candidate genes involved in oestrogen signalling and tamoxifen metabolism might be associated with tamoxifen effects in bone. METHODS: A total of 297 women who were initiating tamoxifen therapy were enrolled in a prospective multicentre clinical trial. Lumbar spine and total hip BMD values were measured using dual-energy X-ray absorptiometry (DXA) at baseline and after 12 months of tamoxifen therapy. Single-nucleotide polymorphisms (SNPs) in ESR1, ESR2, and CYP2D6 were tested for associations in the context of menopausal status and previous chemotherapy, with a mean percentage change in BMD over 12 months. RESULTS: The percentage increase in BMD was greater in postmenopausal women and in those patients who had been treated with chemotherapy. No significant associations between tested SNPs and either baseline BMD or change in BMD with 1 year of tamoxifen therapy were detected. CONCLUSION: The evaluated SNPs in ESR and CYP2D6 do not seem to influence BMD in tamoxifen-treated subjects.

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“…Bisphosphonates significantly prevent bone loss and osteoporotic fractures in postmenopausal women (Storm et al, 1990;Watts et al, 1990;Harris et al, 1993;Liberman et al, 1995;Black et al, 1996;Karpf et al, 1997;Cummings et al, 1998;Hosking et al, 1998). Tamoxifen has an oestrogen-agonistic effect on bone and therefore also prevents bone loss in postmenopausal women (Love et al, 1992;Ward et al, 1993;Kristensen et al, 1994;Grey et al, 1995;Powles et al, 1996). Women with breast cancer are usually recommended to discontinue previous HRT due to the fear of increasing the risk of breast cancer recurrence.…”

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confidence: 99%

The effect of clodronate and antioestrogens on bone loss associated with oestrogen withdrawal in postmenopausal women with breast cancer

et al. 2001

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SummaryIn this study we report bone mineral density (BMD) changes during clodronate and antioestrogen treatment in women with breast cancer having discontinued hormone replacement therapy (HRT) at the time of operation compared to women who had not used HRT immediately before the operation. 61 postmenopausal women with operable breast cancer were treated with the adjuvant antioestrogen tamoxifen 20 mg or toremifene 60 mg daily for 3 years. All patients were randomized to clodronate (1.6 g daily orally) or control groups for 3 years. 23 patients had recently (recent users) and 38 never or not for at least 1 year before operation used HRT (non-users). BMD of lumbar spine and femoral neck were measured before antiresorptive therapy (antioestrogens and clodronate) and at 1, 2, 3 and 5 years thereafter. All patients were disease-free at the time of BMD measurements. Patients who had recently used HRT had more significant bone loss as compared to HRT non-users at 3 years in lumbar spine -3.0% vs. + 1.2% (P < 0.001), but not in femoral neck -0.4% vs. + 1.7% (P = 0.27). Adding 3-year clodronate treatment to antioestrogen therapy improved BMD marginally at 3 years: lumbar spine + 1.0% vs. -1.7% (P = 0.01) and femoral neck + 2.4% vs. -0.4% (P = 0.12). This was also seen at 5 years of follow-up, 2 years after termination of the antiresorptive therapy: HRT recent users vs. HRT non-users in lumbar spine -6.5% vs. +0.5% (P < 0.0001) and in femoral neck -4.8% vs. -1.5% (P = 0.38); and clodronate vs. controls in lumbar spine -1.0% vs. -3.2% (P = 0.06) and in femoral neck -0.1% vs. -5.2% (P = 0.001, respectively). The type of endocrine therapy (tamoxifen and toremifene) had no significant influence on BMD changes. We conclude from this study that postmenopausal women who have recently discontinued HRT experience more rapid bone loss than HRT non-users. Neither 3-year antioestrogen therapy alone nor antioestrogen together with clodronate could totally prevent the bone loss related to HRT withdrawal in lumbar spine, even though clodronate seemed to retard it.

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Tamoxifen and bone metabolism in postmenopausal low-risk breast cancer patients: a randomized study.

Abstract: Tamoxifen has estrogen-like effects on bone metabolism that result in an increase and stabilization of bone mineral density in the axial skeleton and a stabilization of bone mineral content in the appendicular skeleton.

Cited by 201 publications

References 19 publications

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

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

Lack of association between oestrogen receptor polymorphisms and change in bone mineral density with tamoxifen therapy

The effect of clodronate and antioestrogens on bone loss associated with oestrogen withdrawal in postmenopausal women with breast cancer

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