Summary
The anti-estrogen tamoxifen is the prevalent endocrine treatment in postmenopausal breast cancer patients. However, nothing is known about the long-term effects of the drug on the skeleton as assessed by the occurrence of fractures.
We investigated the occurrence of fractures of the femur in patients from a Danish Breast Cancer Cooperative Group (DBCG) trial initiated in 1977 by a linkage of data from the Danish National Registry of Patients with data from the DBCG registry. 1716 postmenopausal women with high-risk breast cancer were randomized to local radiotherapy with or without tamoxifen, 30 mg daily for 1 year.
Fifty-one patients in the control group had one femoral fracture and 64 tamoxifen treated patients had one femoral fracture. Eleven patients in the control group had one trochanteric fracture compared to 27 patients in the tamoxifen group (logrank = 5.28, P = 0.022; hazard ratio = 2.12, 95% CL 1.12, 4.01).
The results could not be explained by a longer survival in the tamoxifen group nor by bone metastases with pathological fractures.
In conclusion, our study suggests that tamoxifen does not seem to offer protection against fractures in old age and may even increase the risk of fractures at particular sites. This hypothesis needs to be disproved or confirmed in other trials.
References
Early Breast Cancer Trialists' Collaborative Group: Systemic treatment of early breast cancer by hormonal, cytotoxic, or immune therapy. Lancet 339: 1–15, 1992
Kristensen B, Ejlertsen B, Dalgaard P, Larsen L, Holmegaard SN, Transboel I, Mouridsen HT: Tamoxifen and bone metabolism in postmenopausal low-risk breast cancer patients: a randomized study. J Clin Oncol 12: 992–997, 1994
Love R, Barden HS, Mazess RB, Epstein S, Chappell RJ: Effect of tamoxifen on lumbar spine bone mineral density in postmenopausal women after 5 years. Arch Int Med 154: 2585–2588, 1994
Fischerman K, Mouridsen HT: Danish breast cancer cooperative group (DBCG). Structure and results of the organization. Acta Oncol 27: 593–596, 1988
Jürgensen HJ, Frœlund C, Gustafsen J, Mosbech H, Guldhammer B, Mosbech J: Registration of diagnoses in the Danish National Registry of Patients. Methods of Information in Medicine 25: 158–164, 1986
Sundhedstyrelsen: Evaluering af Landspatientregisteret 1990. Sygehusstatistik II: 57, 1993
Mouridsen HT, Rose C, Overgaard M, Dombernowsky P, Panduro J, Thorpe S, Rasmussen BB, Blichert-Toft M, Andersen KW: Adjuvant treatment of postmenopausal patients with high risk primary breast cancer. Results from the Danish adjuvant trials DBCG 77 C and DBCG 82 C. Acta Oncol 27: 699–705, 1988
Keeting PE, Scott RE, Colvard DS, Han IK, Spelsberg TC, Riggs BL: Lack of a direct effect of estrogen on proliferation and differentiation of normal human osteoblast-like cells. J Bone Miner Res 6: 297–304, 1991
Ernst M, Parker MG, Rodan GA: Functional estrogen receptors in osteoblastic cells demonstrated by transfection with a reporter gene containing an estrogen response element. Mol Endo 5: 1597–1606, 1991
Al-Azzawi F, Hart DM, Lindsay R: Long term effect of oestrogen replacement therapy on bone mass as measured by dual photon absorptiometry. BMJ 294: 1261–1262, 1987
Escaleira MT, Sonohara S, Brentani MM: Sex steroids induced up-regulation of 1,25-(OH)2 vitamin D3 receptors in T47D breast cancer cells. J Steroid Biochem Mol Biol 45: 257–263, 1993
Speirs V, Adams ER, White MC: The anti-estrogen tamoxifen blocks the stimulatory effects of interleukin-6 on 17 beta-hydroxysteroid dehydrogenase activity in MCF-7 cells. J Steroid Biochem Mol Biol 46: 605–613, 1993
Riggs BL, Hodgson SF, O'Fallon WM, Chao EYS, Wahner HW, Muhs JM, Cedel SL, Melton LJ: Effect of fluoride treatment on the fracture rate in postmenopausal women with osteoporosis. N Engl J Med 322: 802–809, 1990
Ellenberg SS: Surrogate endpoints. Br J Cancer 68: 457–459, 1993
Ryan PJ, Evans P, Blake GM, Fogelman I: The effect of vertebral collapse on spinal bone mineral density measurements in osteoporosis. Bone Miner 18: 267–272, 1992
Sato M, McClintock C, Kim J, Turner CH, Bryant HU, Magee D, Slemenda CW: Dual-energy X-ray absorptiometry of raloxifene effects on the lumbar vertebrae and femora of ovariectomized rats. J Bone Miner Res 9: 715–724, 1994
Evans G, Bryant HU, Magee D, Sato M, Turner RT: The effects of raloxifene on tibia histomorphometry in ovariectomized rats. Endocrinology 134: 2283–2288, 1994
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Kristensen, B., Ejlertsen, B., Mouridsen, H.T. et al. Femoral fractures in postmenopausal breast cancer patients treated with adjuvant tamoxifen. Breast Cancer Res Tr 39, 321–326 (1996). https://doi.org/10.1007/BF01806160
Issue Date:
DOI: https://doi.org/10.1007/BF01806160