The impact of menopause on bone, zoledronic acid, and implications for breast cancer growth and metastasis

Annals of Oncology

Volumn 23, Issue 11, 2012, Pages 2782-2790

  Hadji, P ^a   Coleman, R ^b   Gnant, M ^c   Green, J R ^d  

^a PHILIPPS UNIVERSITY MARBURG   (Germany)

^b WESTON PARK HOSPITAL   (United Kingdom)

^c MEDICAL UNIVERSITY OF VIENNA   (Austria)

^d NOVARTIS PHARMA AG   (Switzerland)

Author keywords

Anticancer; Breast cancer; Endocrine; Estrogen; Hormones; Zoledronic acid

Indexed keywords

EID: 84868115722     PISSN: 09237534     EISSN: 15698041     Source Type: Journal    
DOI: 10.1093/annonc/mds169     Document Type: Review

References (105)

1. Coleman RE, Marshall H, Cameron D et al. Breast-cancer adjuvant therapy with zoledronic acid. N Engl J Med 2011; 365: 1396-1405.
2. Gnant M, Mlineritsch B, Schippinger W et al. Endocrine therapy plus zoledronic acid in premenopausal breast cancer. N Engl J Med 2009; 360: 679-691.
3. Hackshaw A, Baum M, Fornander T et al. Long-term effectiveness of adjuvant goserelin in premenopausal women with early breast cancer. J Natl Cancer Inst 2009; 101: 341-349.
4. Gnant M, Mlineritsch B, Luschin-Ebengreuth G et al. Long-term follow-up in ABCSG-12: significantly improved overall survival with adjuvant zoledronic acid in premenopausal patients with hormone-receptor-positive early breast cancer. In 34th Annual San Antonio Breast Cancer Symposium (Abstr S1-2). San Antonio, TX, 2011.
5. Del Mastro L, Venturini M, Sertoli MR et al. Amenorrhea induced by adjuvant chemotherapy in early breast cancer patients: prognostic role and clinical implications. Breast Cancer Res Treat 1997; 43: 183-190.
6. Gnant M. Bisphosphonates in the prevention of disease recurrence: current results and ongoing trials. Curr Cancer Drug Targets 2009; 9: 824-833.
7. Jimenez-Gordo AM, de las Heras B, Zamora P et al. Failure of goserelin ovarian ablation in premenopausal women with breast cancer: two case reports. Gynecol Oncol 2000; 76: 126-127.
8. Uncu G, Benderli S, Esmer A. Pregnancy during gonadotrophin-releasing hormone agonist therapy. Aust N Z J Obstet Gynaecol 1996; 36: 484-485.
9. Bundred NJ, Campbell ID, Davidson N et al. Effective inhibition of aromatase inhibitor-associated bone loss by zoledronic acid in postmenopausal women with early breast cancer receiving adjuvant letrozole: ZO-FAST study results. Cancer 2008; 112: 1001-1010.
10. de Boer RH, Bundred N, Eidtmann H et al. Long-term survival outcomes among postmenopausal women with hormone receptor-positive early breast cancer receiving adjuvant letrozole and zoledronic acid: 5-year follow-up of ZOFAST. In 34th Annual San Antonio Breast Cancer Symposium (Abstr S1-3). San Antonio, TX, 2011.
11. Dixon JM, Renshaw L, Young O et al. Letrozole suppresses plasma estradiol and estrone sulphate more completely than anastrozole in postmenopausal women with breast cancer. J Clin Oncol 2008; 26: 1671-1676.
12. Geisler J, Haynes B, Anker G et al. Influence of letrozole and anastrozole on total body aromatization and plasma estrogen levels in postmenopausal breast cancer patients evaluated in a randomized, cross-over study. J Clin Oncol 2002; 20: 751-757.
13. Bourdeau V, Deschenes J, Metivier R et al. Genome-wide identification of high-affinity estrogen response elements in human and mouse. Mol Endocrinol 2004; 18: 1411-1427.
14. Tang S, Tan SL, Ramadoss SK et al. Computational method for discovery of estrogen responsive genes. Nucleic Acids Res 2004; 32: 6212-6217.
15. Skerjanec A, Berenson J, Hsu C et al. The pharmacokinetics and pharmacodynamics of zoledronic acid in cancer patients with varying degrees of renal function. J Clin Pharmacol 2003; 43: 154-162.
16. Weiss HM, Pfaar U, Schweitzer A et al. Biodistribution and plasma protein binding of zoledronic acid. Drug Metab Dispos 2008; 36: 2043-2049.
17. Coxon FP, Thompson K, Roelofs AJ et al. Visualizing mineral binding and uptake of bisphosphonate by osteoclasts and non-resorbing cells. Bone 2008; 42: 848-860.
18. Thompson K, Rogers MJ, Coxon FP et al. Cytosolic entry of bisphosphonate drugs requires acidification of vesicles after fluid-phase endocytosis. Mol Pharmacol 2006; 69: 1624-1632.
19. Roelofs AJ, Thompson K, Ebetino FH et al. Bisphosphonates: molecular mechanisms of action and effects on bone cells, monocytes and macrophages. Curr Pharm Des 2010; 16: 2950-2960.
20. Monkkonen H, Kuokkanen J, Holen I et al. Bisphosphonate-induced ATP analog formation and its effect on inhibition of cancer cell growth. Anticancer Drugs 2008; 19: 391-399.
21. Shipman CM, Rogers MJ, Vanderkerken K et al. Bisphosphonates- mechanisms of action in multiple myeloma. Acta Oncol 2000; 39: 829-835.
22. Rogers MJ, Gordon S, Benford HL et al. Cellular and molecular mechanisms of action of bisphosphonates. Cancer 2000; 88: 2961-2978.
23. Guo RT, Cao R, Liang PH et al. Bisphosphonates target multiple sites in both cis- and trans-prenyltransferases. Proc Natl Acad Sci USA 2007; 104: 10022-10027.
24. Hamilton E, Clay TM, Blackwell KL. New perspectives on zoledronic acid in breast cancer: potential augmentation of anticancer immune response. Cancer Invest 2011; 29: 533-541.
25. Winter MC, Holen I, Coleman RE. Exploring the anti-tumour activity of bisphosphonates in early breast cancer. Cancer Treat Rev 2008; 34: 453-475.
26. Binkley N, Kimmel D, Bruner J et al. Zoledronate prevents the development of absolute osteopenia following ovariectomy in adult rhesus monkeys. J Bone Miner Res 1998; 13: 1775-1782.
27. Gasser JA, Ingold P, Venturiere A et al. Long-term protective effects of zoledronic acid on cancellous and cortical bone in the ovariectomized rat. J Bone Miner Res 2008; 23: 544-551.
28. Hornby SB, Evans GP, Hornby SL et al. Long-term zoledronic acid treatment increases bone structure and mechanical strength of long bones of ovariectomized adult rats. Calcif Tissue Int 2003; 72: 519-527.
29. Gasser JA, Green JR, Shen V et al. A single intravenous administration of zoledronic acid prevents the bone loss and mechanical compromise induced by aromatase inhibition in rats. Bone 2006; 39: 787-795.
30. Pataki A, Muller K, Green JR et al. Effects of short-term treatment with the bisphosphonates zoledronate and pamidronate on rat bone: a comparative histomorphometric study on the cancellous bone formed before, during, and after treatment. Anat Rec 1997; 249: 458-468.
31. Le Goff B, Soltner E, Charrier C et al. A combination of methotrexate and zoledronic acid prevents bone erosions and systemic bone mass loss in collagen induced arthritis. Arthritis Res Ther 2009; 11: R185.
32. Sims NA, Green JR, Glatt M et al. Targeting osteoclasts with zoledronic acid prevents bone destruction in collagen-induced arthritis. Arthritis Rheum 2004; 50: 2338-2346.
33. Lee JI, Kim HW, Rhee WI et al. The beneficial effect of intravenous zoledronic acid therapy following an acute stroke in rats. Bone 2006; 39: 377-382.
34. Podworny NV, Kandel RA, Renlund RC et al. Partial chondroprotective effect of zoledronate in a rabbit model of inflammatory arthritis. J Rheumatol 1999; 26: 1972-1982.
35. Little DG, Peat RA, McEvoy A et al. Zoledronic acid treatment results in retention of femoral head structure after traumatic osteonecrosis in young Wistar rats. J Bone Miner Res 2003; 18: 2016-2022.
36. Muller K, Wiesenberg I, Jaeggi K et al. Effects of the bisphosphonate zoledronate on bone loss in the ovariectomized and in the adjuvant arthritic rat. Arzneimittelforschung 1998; 48: 81-86.
37. Little DG, Smith NC, Williams PR et al. Zoledronic acid prevents osteopenia and increases bone strength in a rabbit model of distraction osteogenesis. J Bone Miner Res 2003; 18: 1300-1307.
38. Peyruchaud O, Winding B, Pecheur I et al. Early detection of bone metastases in a murine model using fluorescent human breast cancer cells: application to the use of the bisphosphonate zoledronic acid in the treatment of osteolytic lesions. J Bone Miner Res 2001; 16: 2027-2034.
39. Hiraga T, Williams PJ, Ueda A et al. Zoledronic acid inhibits visceral metastases in the 4T1/luc mouse breast cancer model. Clin Cancer Res 2004; 10: 4559-4567.
40. Giraudo E, Inoue M, Hanahan D. An amino-bisphosphonate targets MMP-9-expressing macrophages and angiogenesis to impair cervical carcinogenesis. J Clin Invest 2004; 114: 623-633.
41. Avcu F, Ural AU, Yilmaz MI et al. The bisphosphonate zoledronic acid inhibits the development of plasmacytoma induced in BALB/c mice by intraperitoneal injection of pristane. Eur J Haematol 2005; 74: 496-500.
42. Duivenvoorden WC, Vukmirovic-Popovic S, Kalina M et al. Effect of zoledronic acid on the doxycycline-induced decrease in tumour burden in a bone metastasis model of human breast cancer. Br J Cancer 2007; 96: 1526-1531.
43. Melani C, Sangaletti S, Barazzetta FM et al. Amino-biphosphonate-mediated MMP-9 inhibition breaks the tumor-bone marrow axis responsible for myeloidderived suppressor cell expansion and macrophage infiltration in tumor stroma. Cancer Res 2007; 67: 11438-11446.
44. Arrington SA, Damron TA, Mann KA et al. Concurrent administration of zoledronic acid and irradiation leads to improved bone density, biomechanical strength, and microarchitecture in a mouse model of tumor-induced osteolysis. J Surg Oncol 2008; 97: 284-290.
45. Ottewell PD, Deux B, Monkkonen H et al. Differential effect of doxorubicin and zoledronic acid on intraosseous versus extraosseous breast tumor growth in vivo. Clin Cancer Res 2008; 14: 4658-4666.
46. Ottewell PD, Lefley DV, Cross SS et al. Sustained inhibition of tumor growth and prolonged survival following sequential administration of doxorubicin and zoledronic acid in a breast cancer model. Int J Cancer 2010; 126: 522-532.
47. Ottewell PD, Monkkonen H, Jones M et al. Antitumor effects of doxorubicin followed by zoledronic acid in a mouse model of breast cancer. J Natl Cancer Inst 2008; 100: 1167-1178.
48. Labrinidis A, Hay S, Liapis V et al. Zoledronic acid inhibits both the osteolytic and osteoblastic components of osteosarcoma lesions in a mouse model. Clin Cancer Res 2009; 15: 3451-3461.
49. Coscia M, Quaglino E, Iezzi M et al. Zoledronic acid repolarizes tumourassociated macrophages and inhibits mammary carcinogenesis by targeting the mevalonate pathway. J Cell Mol Med 2010; 14: 2803-2815.
50. Croucher PI, De Hendrik R, Perry MJ et al. Zoledronic acid treatment of 5T2MM-bearing mice inhibits the development of myeloma bone disease: evidence for decreased osteolysis, tumor burden and angiogenesis, and increased survival. J Bone Miner Res 2003; 18: 482-492.
51. Chapman I, Greville H, Ebeling PR et al. Intravenous zoledronate improves bone density in adults with cystic fibrosis (CF). Clin Endocrinol (Oxf) 2009; 70: 838-846.
52. Black DM, Delmas PD, Eastell R et al. Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. N Engl J Med 2007; 356: 1809-1822.
53. Brown JE, Ellis SP, Lester JE et al. Prolonged efficacy of a single dose of the bisphosphonate zoledronic acid. Clin Cancer Res 2007; 13: 5406-5410.
54. Hershman DL, McMahon DJ, Crew KD et al. Zoledronic acid prevents bone loss in premenopausal women undergoing adjuvant chemotherapy for earlystage breast cancer. J Clin Oncol 2008; 26: 4739-4745.
55. Hershman DL, McMahon DJ, Crew KD et al. Prevention of bone loss by zoledronic acid in premenopausal women undergoing adjuvant chemotherapy persist up to one year following discontinuing treatment. J Clin Endocrinol Metab 2010; 95: 559-566.
56. Hines SL, Sloan JA, Atherton PJ et al. Zoledronic acid for treatment of osteopenia and osteoporosis in women with primary breast cancer undergoing adjuvant aromatase inhibitor therapy. Breast 2010; 19: 92-96.
57. Gnant M. Targeted therapies: adjuvant bisphosphonates-an option with low estrogen. Nat Rev Clin Oncol 2011; 8: 698-699.
58. Kaplan RN, Rafii S, Lyden D. Preparing the "soil": the premetastatic niche. Cancer Res 2006; 66: 11089-11093.
59. Wels J, Kaplan RN, Rafii S et al. Migratory neighbors and distant invaders: tumor-associated niche cells. Genes Dev 2008; 22: 559-574.
60. Kaplan RN, Riba RD, Zacharoulis S et al. VEGFR1-positive haematopoietic bone marrow progenitors initiate the pre-metastatic niche. Nature 2005; 438: 820-827.
61. Meads MB, Hazlehurst LA, Dalton WS. The bone marrow microenvironment as a tumor sanctuary and contributor to drug resistance. Clin Cancer Res 2008; 14: 2519-2526.
62. Shiozawa Y, Havens AM, Pienta KJ et al. The bone marrow niche: habitat to hematopoietic and mesenchymal stem cells, and unwitting host to molecular parasites. Leukemia 2008; 22: 941-950.
63. Gordon CM, LeBoff MS, Glowacki J. Adrenal and gonadal steroids inhibit IL-6 secretion by human marrow cells. Cytokine 2001; 16: 178-186.
64. Bilezikjian LM, Blount AL, Leal AM et al. Autocrine/paracrine regulation of pituitary function by activin, inhibin and follistatin. Mol Cell Endocrinol 2004; 225: 29-36.
65. Centrella M, McCarthy TL, Canalis E. Transforming growth factor-beta and remodeling of bone. J Bone Joint Surg Am 1991; 73: 1418-1428.
66. Juarez P, Guise TA. TGF-beta in cancer and bone: implications for treatment of bone metastases. Bone 2011; 48: 23-29.
67. Hampl R, Snajderova M, Mardesic T. Antimullerian hormone (AMH) not only a marker for prediction of ovarian reserve. Physiol Res 2011; 60: 217-223.
68. Cheleuitte D, Mizuno S, Glowacki J. In vitro secretion of cytokines by human bone marrow: effects of age and estrogen status. J Clin Endocrinol Metab 1998; 83: 2043-2051.
69. Sasser AK, Sullivan NJ, Studebaker AW et al. Interleukin-6 is a potent growth factor for ER-alpha-positive human breast cancer. FASEB J 2007; 21: 3763-3770.
70. Sasser AK, Mundy BL, Smith KM et al. Human bone marrow stromal cells enhance breast cancer cell growth rates in a cell line-dependent manner when evaluated in 3D tumor environments. Cancer Lett 2007; 254: 255-264.
71. Studebaker AW, Storci G, Werbeck JL et al. Fibroblasts isolated from common sites of breast cancer metastasis enhance cancer cell growth rates and invasiveness in an interleukin-6-dependent manner. Cancer Res 2008; 68: 9087-9095.
72. Esparza-Lopez J, Montiel JL, Vilchis-Landeros MM et al. Ligand binding and functional properties of betaglycan, a co-receptor of the transforming growth factor-beta superfamily. Specialized binding regions for transforming growth factor-beta and inhibin A. J Biol Chem 2001; 276: 14588-14596.
73. Kirkbride KC, Townsend TA, Bruinsma MW et al. Bone morphogenetic proteins signal through the transforming growth factor-beta type III receptor. J Biol Chem 2008; 283: 7628-7637.
74. Lewis KA, Gray PC, Blount AL et al. Betaglycan binds inhibin and can mediate functional antagonism of activin signalling. Nature 2000; 404: 411-414.
75. Nicks KM, Fowler TW, Akel NS et al. Bone turnover across the menopause transition: the role of gonadal inhibins. Ann N Y Acad Sci 2010; 1192: 153-160.
76. Rosen V. BMP and BMP inhibitors in bone. Ann N Y Acad Sci 2006; 1068: 19-25.
77. Wiater E, Vale W. Inhibin is an antagonist of bone morphogenetic protein signaling. J Biol Chem 2003; 278: 7934-7941.
78. Perrien DS, Achenbach SJ, Bledsoe SE et al. Bone turnover across the menopause transition: correlations with inhibins and follicle-stimulating hormone. J Clin Endocrinol Metab 2006; 91: 1848-1854.
79. Perrien DS, Akel NS, Edwards PK et al. Inhibin A is an endocrine stimulator of bone mass and strength. Endocrinology 2007; 148: 1654-1665.
80. Bismar H, Diel I, Ziegler R et al. Increased cytokine secretion by human bone marrow cells after menopause or discontinuation of estrogen replacement. J Clin Endocrinol Metab 1995; 80: 3351-3355.
81. Chiu KM, Ju J, Mayes D et al. Changes in bone resorption during the menstrual cycle. J Bone Miner Res 1999; 14: 609-615.
82. Clowes JA, Eghbali-Fatourechi GZ, McCready L et al. Estrogen action on bone marrow osteoclast lineage cells of postmenopausal women in vivo. Osteoporos Int 2009; 20: 761-769.
83. Rosen CJ, Verault D, Steffens C et al. Effects of age and estrogen status on the skeletal IGF regulatory system. Studies with human marrow. Endocrine 1997; 7: 77-80.
84. Sirola J, Kroger H, Honkanen R et al. Factors affecting bone loss around menopause in women without HRT: a prospective study. Maturitas 2003; 45: 159-167.
85. Hofbauer LC, Khosla S, Dunstan CR et al. Estrogen stimulates gene expression and protein production of osteoprotegerin in human osteoblastic cells. Endocrinology 1999; 140: 4367-4370.
86. Lindberg MK, Erlandsson M, Alatalo SL et al. Estrogen receptor alpha, but not estrogen receptor beta, is involved in the regulation of the OPG/RANKL (osteoprotegerin/receptor activator of NF-kappa B ligand) ratio and serum interleukin-6 in male mice. J Endocrinol 2001; 171: 425-433.
87. Rachner TD, Schoppet M, Niebergall U et al. 17beta-Estradiol inhibits osteoprotegerin production by the estrogen receptor-alpha-positive human breast cancer cell line MCF-7. Biochem Biophys Res Commun 2008; 368: 736-741.
88. Saika M, Inoue D, Kido S et al. 17beta-estradiol stimulates expression of osteoprotegerin by a mouse stromal cell line, ST-2, via estrogen receptor-alpha. Endocrinology 2001; 142: 2205-2212.
89. Ibrahim T, Mercatali L, Sacanna E et al. Circulating levels of RANK/RANKL and OPG in patients with bone metastases treated with zoledronic acid: a prospective study. In 2011 ASCO Annual Meeting (Abstr 10611). Chicago, IL, 2011.
90. Burger HG, Dudley EC, Robertson DM et al. Hormonal changes in the menopause transition. Recent Prog Horm Res 2002; 57: 257-275.
91. Baum M, Budzar AU, Cuzick J et al. Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of postmenopausal women with early breast cancer: first results of the ATAC randomised trial. Lancet 2002; 359: 2131-2139.
92. Thurlimann B, Keshaviah A, Coates AS et al. A comparison of letrozole and tamoxifen in postmenopausal women with early breast cancer. N Engl J Med 2005; 353: 2747-2757.
93. van de Velde CJ, Rea D, Seynaeve C et al. Adjuvant tamoxifen and exemestane in early breast cancer (TEAM): a randomised phase 3 trial. Lancet 2011; 377: 321-331.
94. Welt CK, McNicholl DJ, Taylor AE et al. Female reproductive aging is marked by decreased secretion of dimeric inhibin. J Clin Endocrinol Metab 1999; 84: 105-111.
95. Rannevik G, Jeppsson S, Johnell O et al. A longitudinal study of the perimenopausal transition: altered profiles of steroid and pituitary hormones, SHBG and bone mineral density. Maturitas 2008; 61: 67-77.
96. Sowers MR, Zheng H, McConnell D et al. Estradiol rates of change in relation to the final menstrual period in a population-based cohort of women. J Clin Endocrinol Metab 2008; 93: 3847-3852.
97. Folkerd EJ, Dowsett M. Influence of sex hormones on cancer progression. J Clin Oncol 2010; 28: 4038-4044.
98. Burger HG, Cahir N, Robertson DM et al. Serum inhibins A and B fall differentially as FSH rises in perimenopausal women. Clin Endocrinol (Oxf) 1998; 48: 809-813.
99. Sun L, Peng Y, Sharrow AC et al. FSH directly regulates bone mass. Cell 2006; 125: 247-260.
100. Khosla S, Melton LJ, III, Achenbach SJ et al. Hormonal and biochemical determinants of trabecular microstructure at the ultradistal radius in women and men. J Clin Endocrinol Metab 2006; 91: 885-891.
101. Pfeilschifter J, Diel I, Scheppach B et al. Concentration of transforming growth factor beta in human bone tissue: relationship to age, menopause, bone turnover, and bone volume. J Bone Miner Res 1998; 13: 716-730.
102. Edlund S, Landstrom M, Heldin CH et al. Transforming growth factor-betainduced mobilization of actin cytoskeleton requires signaling by small GTPases Cdc42 and RhoA. Mol Biol Cell 2002; 13: 902-914.
103. Edlund S, Landstrom M, Heldin CH et al. Smad7 is required for TGF-betainduced activation of the small GTPase Cdc42. J Cell Sci 2004; 117: 1835-1847.
104. Kardassis D, Murphy C, Fotsis T et al. Control of transforming growth factor beta signal transduction by small GTPases. FEBS J 2009; 276: 2947-2965.
105. Ogata S, Morokuma J, Hayata T et al. TGF-beta signaling-mediated morphogenesis: modulation of cell adhesion via cadherin endocytosis. Genes Dev 2007; 21: 1817-1831.