Role of bisphosphonates in postmenopausal women with breast cancer

Cancer Treatment Reviews

Volumn 40, Issue 3, 2014, Pages 476-484

  Gnant, Michael ^a  

^a MEDICAL UNIVERSITY OF VIENNA   (Austria)

Author keywords

Adjuvant therapy; Anticancer; Bisphosphonate; Bone mineral density; Breast cancer; Clodronate; Survival; Zoledronic acid

Indexed keywords

ANTINEOPLASTIC AGENT; BISPHOSPHONIC ACID DERIVATIVE;

BREAST CANCER; CLINICAL RESEARCH; EMBASE; HUMAN; MEDLINE; POSTMENOPAUSE; REVIEW; TRANSLATIONAL RESEARCH;

ADJUVANT THERAPY; ANTICANCER; BISPHOSPHONATE; BONE MINERAL DENSITY; BREAST CANCER; CLODRONATE; SURVIVAL; ZOLEDRONIC ACID;

BONE DENSITY CONSERVATION AGENTS; BREAST NEOPLASMS; DIPHOSPHONATES; FEMALE; HUMANS; OSTEOPOROSIS, POSTMENOPAUSAL; POSTMENOPAUSE;

EID: 84892880906     PISSN: 03057372     EISSN: 15321967     Source Type: Journal    
DOI: 10.1016/j.ctrv.2013.07.003     Document Type: Review

References (77)

1. National Cancer Institute. Surveillance Epidemiology and End Results (SEER) Cancer Statistics Review, 1975-2007. <>. http://seer.cancer.gov/csr/1975_2007/.
2. American Cancer Society. Cancer Facts and Figures 2012. <>. http://www.cancer.org/Research/CancerFactsFigures/CancerFactsFigures/cancer-facts-figures-2012.
3. Abdel-Razeq H., Awidi A. Bone health in breast cancer survivors. J Cancer Res Ther 2011, 7(3):256-263.
4. Mundy G.R. Cellular and molecular regulation of bone turnover. Bone 1999, 24(Suppl 5):8S-35S.
5. Lester J., Dodwell D., McCloskey E., Coleman R. The causes and treatment of bone loss associated with carcinoma of the breast. Cancer Treat Rev 2005, 31(2):115-142.
6. Guise T.A., Brufsky A., Coleman R.E. Understanding and optimizing bone health in breast cancer. Curr Med Res Opin 2010, 26(Suppl 3):3-20.
7. Russell R.G. Bisphosphonates: mode of action and pharmacology. Pediatrics 2007, 119(Suppl 2):S62-S150.
8. Guise T.A. Bone loss and fracture risk associated with cancer therapy. Oncologist 2006, 11(10):1121-1131.
9. Gnant M., Dubsky P., Hadji P. Bisphosphonates: prevention of bone metastases in breast cancer. Recent Results Cancer Res 2012, 192:65-91.
10. Hadji P., Aapro M.S., Body J.J., et al. Management of aromatase inhibitor-associated bone loss in postmenopausal women with breast cancer: practical guidance for prevention and treatment. Ann Oncol 2011, 22(12):2546-2555.
11. Bundred N.J., Campbell I.D., 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(5):1001-1010.
12. Eastell R., Adams J.E., Coleman R.E., et al. Effect of anastrozole on bone mineral density: 5-year results from the anastrozole, tamoxifen, alone or in combination trial 18233230. J Clin Oncol 2008, 26(7):1051-1057.
13. Greenspan S.L., Brufsky A., Lembersky B.C., et al. Risedronate prevents bone loss in breast cancer survivors: a 2-year, randomized, double-blind, placebo-controlled clinical trial. J Clin Oncol 2008, 26(16):2644-2652.
14. Van Poznak C., Hannon R.A., Mackey J.R., et al. Prevention of aromatase inhibitor-induced bone loss using risedronate: the SABRE trial. J Clin Oncol 2010, 28(6):967-975.
15. Markopoulos C., Tzoracoleftherakis E., Polychronis A., et al. Management of anastrozole-induced bone loss in breast cancer patients with oral risedronate: results from the ARBI prospective clinical trial. Breast Cancer Res 2010, 12(2):R24.
16. Cohen A., Fleischer J.B., Johnson M.K., et al. Prevention of bone loss after withdrawal of tamoxifen. Endocr Pract 2008, 14(2):162-167.
17. Lester J.E., Dodwell D., Purohit O.P., et al. Prevention of anastrozole-induced bone loss with monthly oral ibandronate during adjuvant aromatase inhibitor therapy for breast cancer. Clin Cancer Res 2008, 14(19):6336-6342.
18. Lee S.A., Hwang S.H., Ahn S.G., Lee H.M., Jeong J., Lee H.D. Effects of zoledronic acid on bone mineral density during aromatase inhibitor treatment of Korean postmenopausal breast cancer patients. Breast Cancer Res Treat 2011, 130(3):863-870.
19. Hines S.L., Sloan J.A., Atherton P.J., et al. Zoledronic acid for treatment of osteopenia and osteoporosis in women with primary breast cancer undergoing adjuvant aromatase inhibitor therapy. Breast 2010, 19(2):92-96.
20. Hines S.L., Mincey B., Dentchev T., et al. Immediate versus delayed zoledronic acid for prevention of bone loss in postmenopausal women with breast cancer starting letrozole after tamoxifen-N03CC. Breast Cancer Res Treat 2009, 117(3):603-609.
21. Llombart A., Frassoldati A., Paija O., et al. Immediate administration of zoledronic acid reduces aromatase inhibitor-associated bone loss in postmenopausal women with early breast cancer: 12-month analysis of the E-ZO-FAST trial. Clin Breast Cancer 2012, 12(1):40-48.
22. Brufsky A., Bundred N., Coleman R., et al. Integrated analysis of zoledronic acid for prevention of aromatase inhibitor-associated bone loss in postmenopausal women with early breast cancer receiving adjuvant letrozole. Oncologist 2008, 13(5):503-514.
23. Leal T., Tevaarwerk A., Love R., et al. Randomized trial of adjuvant zoledronic acid in postmenopausal women with high-risk breast cancer. Clin Breast Cancer 2010, 10(6):471-476.
24. Brufsky A.M., Bosserman L.D., Caradonna R.R., et al. Zoledronic acid effectively prevents aromatase inhibitor-associated bone loss in postmenopausal women with early breast cancer receiving adjuvant letrozole: Z-FAST study 36-month follow-up results. Clin Breast Cancer 2009, 9(2):77-85.
25. Brufsky A.M., Harker W.G., Beck J.T., et al. Final 5-year results of Z-FAST trial: adjuvant zoledronic acid maintains bone mass in postmenopausal breast cancer patients receiving letrozole. Cancer 2012, 118(5):1192-1201.
26. Coleman R., de Boer R., Eidtmann H., et al. Zoledronic acid (zoledronate) for postmenopausal women with early breast cancer receiving adjuvant letrozole (ZO-FAST study): final 60-month results. Ann Oncol 2013, 24(2):398-405.
27. Valachis A., Polyzos N.P., Georgoulias V., Mavroudis D., Mauri D. Lack of evidence for fracture prevention in early breast cancer bisphosphonate trials: a meta-analysis. Gynecol Oncol 2010, 117(1):139-145.
28. van Londen G.J., Perera S., Vujevich K.T., Sereika S.M., Bhattacharya R., Greenspan S.L. Effect of risedronate on hip structural geometry: a 1-year, double-blind trial in chemotherapy-induced postmenopausal women. Bone 2008, 43(2):274-278.
29. van Londen G.J., Perera S., Vujevich K.T., Sereika S.M., Bhattacharya R., Greenspan S.L. The effect of risedronate on hip structural geometry in chemotherapy-induced postmenopausal women with or without use of aromatase inhibitors: a 2-year trial. Bone 2010, 46(3):655-659.
30. Love R.R., Mazess R.B., Barden H.S., et al. Effects of tamoxifen on bone mineral density in postmenopausal women with breast cancer. N Engl J Med 1992, 326(13):852-856.
31. Resch A., Biber E., Seifert M., Resch H. Evidence that tamoxifen preserves bone density in late postmenopausal women with breast cancer. Acta Oncol 1998, 37(7-8):661-664.
32. Vehmanen L., Saarto T., Elomaa I., Makela P., Valimaki M., Blomqvist C. Long-term impact of chemotherapy-induced ovarian failure on bone mineral density (BMD) in premenopausal breast cancer patients. The effect of adjuvant clodronate treatment. Eur J Cancer 2001, 37(18):2373-2378.
33. Gnant M. 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 [oral; abstract S1-2]. Presented at: 34th Annual San Antonio Breast Cancer Symposium; December 6-10, 2011; San Antonio, TX.
34. Gnant M., Mlineritsch B., Luschin-Ebengreuth G., et al. Adjuvant endocrine therapy plus zoledronic acid in premenopausal women with early-stage breast cancer: 5-year follow-up of the ABCSG-12 bone-mineral density substudy. Lancet Oncol 2008, 9(9):840-849.
35. Diel I.J., Jaschke A., Solomayer E.F., et al. Adjuvant oral clodronate improves the overall survival of primary breast cancer patients with micrometastases to the bone marrow: a long-term follow-up. Ann Oncol 2008, 19(12):2007-2011.
36. Powles T., Paterson A., McCloskey E., et al. Reduction in bone relapse and improved survival with oral clodronate for adjuvant treatment of operable breast cancer [ISRCTN83688026]. Breast Cancer Res 2006, 8(2):R13.
37. Saarto T., Blomqvist C., Virkkunen P., Elomaa I. Adjuvant clodronate treatment does not reduce the frequency of skeletal metastases in node-positive breast cancer patients: 5-year results of a randomized controlled trial. J Clin Oncol 2001, 19(1):10-17.
38. Lipton A., Chapman J.A., Demers L., et al. Elevated bone turnover predicts for bone metastasis in postmenopausal breast cancer: results of NCIC CTG MA.14. J Clin Oncol 2011, 29(27):3605-3610.
39. Gnant M. Zoledronic acid in the treatment of early-stage breast cancer: is there a final verdict?. Curr Oncol Rep 2012, 14(1):35-43.
40. Coleman R.E., Marshall H., Cameron D., et al. Breast-cancer adjuvant therapy with zoledronic acid. N Engl J Med 2011, 365(15):1396-1405.
41. Eidtmann H., de Boer R., Bundred N., et al. Efficacy of zoledronic acid in postmenopausal women with early breast cancer receiving adjuvant letrozole: 36-month results of the ZO-FAST Study. Ann Oncol 2010, 21(11):2188-2194.
42. Möbus V, Diel IJ, Elling D, et al. GAIN study: a phase-III trial to compare ETC. vs. EC-TX and ibandronate vs. observation in patients with node-positive primary breast cancer - 1st interim efficacy analysis [oral; abstract S2-4]. Presented at: 34th Annual San Antonio Breast Cancer Symposium; December 6-10, 2011; San Antonio, TX.
43. Paterson A.H., Anderson S.J., Lembersky B.C., et al. Oral clodronate for adjuvant treatment of operable breast cancer (National Surgical Adjuvant Breast and Bowel Project protocol B-34): a multicentre, placebo-controlled, randomised trial. Lancet Oncol 2012, 13(7):734-742.
44. Paterson AHG, Anderson SJ, Lembersky BC, et al. NSABP Protocol B-34: a clinical trial comparing adjuvant clodronate vs. placebo in early breast cancer patients receiving systemic chemotherapy and/or tamoxifen or no therapy - final analysis [oral; abstract S2-3]. Presented at: 34th Annual San Antonio Breast Cancer Symposium; December 6-10, 2011; San Antonio, TX.
45. Yan T., Yin W., Zhou Q., et al. The efficacy of zoledronic acid in breast cancer adjuvant therapy: a meta-analysis of randomized controlled trials. Eur J Cancer 2012, 48(2):187-195.
46. Chlebowski R.T., Chen Z., Cauley J.A., et al. Oral bisphosphonate use and breast cancer incidence in postmenopausal women. J Clin Oncol 2010, 28(22):3582-3590.
47. Newcomb P.A., Trentham-Dietz A., Hampton J.M. Bisphosphonates for osteoporosis treatment are associated with reduced breast cancer risk. Br J Cancer 2010, 102(5):799-802.
48. Rennert G., Pinchev M., Rennert H.S. Use of bisphosphonates and risk of postmenopausal breast cancer. J Clin Oncol 2010, 28(22):3577-3581.
49. Ripamonti C.I., Maniezzo M., Campa T., et al. Decreased occurrence of osteonecrosis of the jaw after implementation of dental preventive measures in solid tumour patients with bone metastases treated with bisphosphonates. The experience of the National Cancer Institute of Milan. Ann Oncol 2009, 20(1):137-145.
50. Dimopoulos M.A., Kastritis E., Bamia C., et al. Reduction of osteonecrosis of the jaw (ONJ) after implementation of preventive measures in patients with multiple myeloma treated with zoledronic acid. Ann Oncol 2009, 20(1):117-120.
51. Yamashita J., McCauley L.K. Antiresorptives and osteonecrosis of the jaw. J Evid Based Dent Pract 2012, 12(3 Suppl):233-247.
52. McLeod N.M., Brennan P.A., Ruggiero S.L. Bisphosphonate osteonecrosis of the jaw: a historical and contemporary review. Surgeon 2012, 10(1):36-42.
53. Weitzman R., Sauter N., Eriksen E.F., et al. Critical review: updated recommendations for the prevention, diagnosis, and treatment of osteonecrosis of the jaw in cancer patients - May 2006. Crit Rev Oncol Hematol 2007, 62(2):148-152.
54. Wilson C., Holen I., Coleman R.E. Seed, soil and secreted hormones: potential interactions of breast cancer cells with their endocrine/paracrine microenvironment and implications for treatment with bisphosphonates. Cancer Treat Rev 2012, 38(7):877-889.
55. Gnant M., Clezardin P. Direct and indirect anticancer activity of bisphosphonates: a brief review of published literature. Cancer Treat Rev 2012, 38(5):407-415.
56. Holen I, Reeves KJ, Fowles AM, Croucher PI, Eaton CL, Ottewell PD. Zoledronic acid specifically inhibits development of bone metastases in the post-menopausal setting - evidence from an in vivo breast cancer model [poster discussion; abstract PD07-08]. Presented at: 33rd Annual San Antonio Breast Cancer Symposium; December 4-8, 2012; San Antonio, Texas.
57. Coleman RE, Rathbone EJ, Marshall HC, et al. Vitamin D, but not bone turnover markers, predict relapse in women with early breast cancer: an AZURE translational study [abstract S6-4]. Presented at: 35th Annual San Antonio Breast Cancer Symposium; December 4-8, 2012; San Antonio, TX.
58. Wilson C, Winter MC, Holen I, Freeman JV, Evans AC, Coleman RE. The interaction between menopausal status and zoledronic acid can differentially affect serum levels of the TGFβ superfamily [poster; abstract P2-02-04]. Presented at: 35th Annual San Antonio Breast Cancer Symposium; December 4-8, 2012; San Antonio, TX.
59. Amgen. Study of denosumab as adjuvant treatment for women with high risk early breast cancer receiving neoadjuvant or adjuvant therapy (D-CARE). <>. http://www.clinicaltrials.gov/ct2/show/NCT01077154?term=D-CARE&no_unk=Y&rank=1.
60. Southwest Oncology Group. Phase III randomized study of adjuvant zoledronate versus clodronate versus ibandronate in women with resected primary stage I-III adenocarcinoma of the breast. http://www.cancer.gov/clinicaltrials/search/view?cdrid=437061&version=HealthProfessional.
61. Wong M.H., Stockler M.R., Pavlakis N. Bisphosphonates and other bone agents for breast cancer. Cochrane Database Syst Rev 2012, 2:CD003474.
62. Bidard F.C., Vincent-Salomon A., Gomme S., et al. Disseminated tumor cells of breast cancer patients: a strong prognostic factor for distant and local relapse. Clin Cancer Res 2008, 14(11):3306-3311.
63. Aft R., Naughton M., Trinkaus K., et al. Effect of zoledronic acid on disseminated tumour cells in women with locally advanced breast cancer: an open label, randomised, phase 2 trial. Lancet Oncol 2010, 11(5):421-428.
64. Rack B., Juckstock J., Genss E.M., et al. Effect of zoledronate on persisting isolated tumour cells in patients with early breast cancer. Anticancer Res 2010, 30(5):1807-1813.
65. Clézardin P., Ebetino F.H., Fournier P.G.J. Bisphosphonates and cancer-induced bone disease: beyond their antiresorptive activity. Cancer Res 2005, 65(12):4971-4974.
66. Winter M.C., Holen I., Coleman R.E. Exploring the anti-tumour activity of bisphosphonates in early breast cancer. Cancer Treat Rev 2008, 34(5):453-475.
67. Zometa® [summary of product characteristics]. Nuremberg, Germany: Novartis Pharma GmbH; 1997.
68. Manso L, Barnadas A, Tusquets I, et al. AAssociation between circulating tumor cells and bone turnover markers in patients with breast cancer and bone metastases on treatment with bisphosphonates (ZOMAR study) [poster; abstract P2-01-06]. Presented at: 35th Annual San Antonio Breast Cancer Symposium; December 4-8, 2012; San Antonio, TX.
69. Hamilton EP, Hobeika AC, Lyerly HK, et al. Zoledronic acid induces an immune response in breast cancer patients through stimulation of central memory and effector memory gamma/delta T cells [poster; abstract P1-13-03]. Presented at: 34th Annual San Antonio Breast Cancer Symposium; December 6-10, 2011; San Antonio, TX.
70. Sugie T, Tanaka Y, Toi M, Minato N. Immunological effects of bisphosphonates on gamma delta T cells in breast cancer [poster; abstract P1-01-04]. Presented at: 34th Annual San Antonio Breast Cancer Symposium; December 6-10, 2011; San Antonio, TX.
71. Holen I, Ottewell PD, Coleman RE. Zoledronic acid reduces breast tumour growth when combined with chemotherapy - emerging evidence of anti-tumor effects outside bone [poster; abstract P6-14-03]. Presented at: 33rd Annual San Antonio Breast Cancer Symposium; December 8-12, 2010; San Antonio, TX.
72. Misso G., Porru M., Stoppacciaro A., et al. Evaluation of the in vitro and in vivo antiangiogenic effects of denosumab and zoledronic acid. Cancer Biol Ther 2012, 13(14):1491-1500.
73. Coleman R.E., Winter M.C., Cameron D., et al. The effects of adding zoledronic acid to neoadjuvant chemotherapy on tumour response: exploratory evidence for direct anti-tumour activity in breast cancer. Br J Cancer 2010, 102(7):1099-1105.
74. Fasching PA, Jud SM, Hauschild M, et al. Anticancer activity of letrozole plus zoledronic acid as neoadjuvant therapy for postmenopausal patients with breast cancer: FEMZONE trial results [poster discussion; abstract PD-07-02]. Presented at: 35th Annual San Antonio Breast Cancer Symposium; December 4-8, 2012; San Antonio, TX.
75. Winter MC, Syddall SP, Cross SS, et al. ANZAC: a randomized neoadjuvant biomarker study investigating the anti-tumour activity of the addition of zoledronic acid to chemotherapy in breast cancer [poster; abstract P1-11-01]. Presented at: 33rd Annual San Antonio Breast Cancer Symposium; December 8-12, 2010; San Antonio, TX.
76. Borstkanker Onderzoek Groep. Doxorubicin hydrochloride, cyclophosphamide, and docetaxel with or without zoledronic acid in treating patients with large resectable or locally advanced breast cancer. <>. http://www.clinicaltrials.gov/ct2/show/NCT01099436?term=NCT01099436&rank=1.
77. Azim H., Azim H.A. Targeting RANKL in breast cancer: bone metastasis and beyond. Expert Rev Anticancer Ther 2013, 13(2):195-201.