Bone health care in women with breast cancer

Abstract

The aim of this article is to analyze and critically appraise the literature regarding optimal bone health care in women with breast cancer and, more specifically, to present (1) the causes of bone loss in breast cancer patients, (2) the appropriate screening for osteoporosis and fracture risk estimation, (3) optimal prevention and therapeutic strategies for osteoporosis and fractures, (4) the role of antiresorptive agents as adjuvant therapy for the prevention of bone metastases and increase of overall survival, and (5) current data on the possible use of menopausal hormone therapy (MHT) in these patients. The objective is to provide a sound pathophysiological background along with evidence-based and practical recommendations for physicians managing such women.

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  • 22 January 2020

    The original version of this article, published on 18 December 2019, contained a mistake.

References

  1. 1.

    Lüftner D, Niepel D, Steger GG (2018) Therapeutic approaches for protecting bone health in patients with breast cancer. Breast. 37:28–35

    PubMed  Article  Google Scholar 

  2. 2.

    Verdecchia A, Guzzinati S, Francisci S, De Angelis R, Bray F, Allemani C, Tavilla A, Santaquilani M, Sant M; EUROCARE Working Group (1990) Survival trends in European cancer patients diagnosed from 1988 to 1999. Eur J Cancer 45:1042–1066

  3. 3.

    Sant M, Chirlaque Lopez MD, Agresti R, Sánchez Pérez MJ, Holleczek B, Bielska-Lasota M, Dimitrova N, Innos K, Katalinic A, Langseth H, Larrañaga N, Rossi S, Siesling S, Minicozzi P; EUROCARE-5 Working Group (1990) Survival of women with cancers of breast and genital organs in Europe 1999-2007: Results of the EUROCARE-5 study. Eur J Cancer 51:2191–2205

  4. 4.

    National Cancer Institute SEER stat fact sheet: female breast cancer. 2011e2013. Available from: http://seer.cancer.gov/statfacts/html/breast.html (last accessed on 22 June 2019)

  5. 5.

    Trémollieres FA, Ceausu I, Depypere H, Lambrinoudaki I, Mueck A, Pérez-López FR, van der Schouw YT, Senturk LM, Simoncini T, Stevenson JC, Stute P, Rees M (2017) Osteoporosis management in patients with breast cancer: EMAS position statement. Maturitas. 95:65–71

    PubMed  Article  Google Scholar 

  6. 6.

    Coleman R, Body JJ, Aapro M, Hadji P, Herrstedt J, ESMO Guidelines Working Group (2014) Bone health in cancer patients: ESMO Clinical Practice Guidelines. Ann Oncol 25(Suppl 3):124–137

    Article  Google Scholar 

  7. 7.

    Grossmann M, Ramchand SK, Milat F, Vincent A, Lim E, Kotowicz MA, Hicks J, Teede H (2018) Assessment and management of bone health in women with oestrogen receptor-positive breast cancer receiving endocrine therapy: position statement of the Endocrine Society of Australia, the Australian and New Zealand Bone & Mineral Society, the Australasian Menopause Society and the Clinical Oncology Society of Australia. Clin Endocrinol 89:280–296

    Article  Google Scholar 

  8. 8.

    Bainbridge KE, Sowers MF, Crutchfield M, Lin X, Jannausch M, Harlow SD (2002) Natural history of bone loss over 6 years among premenopausal and early postmenopausal women. Am J Epidemiol 156:410e7

    Article  Google Scholar 

  9. 9.

    Eastell R, Hannon RA, Cuzick J, Dowsett M, Clack G (2006) Adams JE; ATAC Trialists’ group. Effect of an aromatase inhibitor on bmd and bone turnover markers: 2-year results of the Anastrozole, Tamoxifen, Alone or in Combination (ATAC) trial (18233230). J Bone Miner Res 21:1215–1223

    CAS  PubMed  Article  Google Scholar 

  10. 10.

    Coleman RE, Banks LM, Girgis SI, Kilburn LS, Vrdoljak E, Fox J, Cawthorn SJ, Patel A, Snowdon CF, Hall E, Bliss JM, Coombes RC (2007) Intergroup Exemestane Study group. Skeletal effects of exemestane on bone-mineral density, bone biomarkers, and fracture incidence in postmenopausal women with early breast cancer participating in the Intergroup Exemestane Study (IES): a randomised controlled study. Lancet Oncol 8:119–127

    CAS  PubMed  Article  Google Scholar 

  11. 11.

    Goss PE, Ingle JN, Martino S, Robert NJ, Muss HB, Piccart MJ, Castiglione M, Tu D, Shepherd LE, Pritchard KI, Livingston RB, Davidson NE, Norton L, Perez EA, Abrams JS, Cameron DA, Palmer MJ, Pater JL (2005) Randomized trial of letrozole following tamoxifen as extended adjuvant therapy in receptor-positive breast cancer: updated findings from NCIC CTG MA.17. J Natl Cancer Inst 97:1262–1271

    CAS  PubMed  Article  Google Scholar 

  12. 12.

    Gonnelli S, Cadirni A, Caffarelli C, Petrioli R, Montagnani A, Franci MB, Lucani B, Francini G, Nuti R (2007) Changes in bone turnover and in bone mass in women with breast cancer switched from tamoxifen to exemestane. Bone. 40:205–210

    CAS  PubMed  Article  Google Scholar 

  13. 13.

    Hadji P, Ziller M, Kieback DG, Dornoff W, Tessen HW, Menschik T, Kuck J, Melchert F, Hasenburg A (2009) Effects of exemestane and tamoxifen on bone health within the Tamoxifen Exemestane Adjuvant Multicentre (TEAM) trial: results of a German, 12-month, prospective, randomised substudy. Ann Oncol 20:1203–1209

    CAS  PubMed  Article  Google Scholar 

  14. 14.

    Hadji P (2009) Aromatase inhibitor-associated bone loss in breast cancer patients is distinct from postmenopausal osteoporosis. Crit Rev Oncol Hematol 69:73–82

    PubMed  Article  Google Scholar 

  15. 15.

    Eastell R, Adams JE, Coleman RE, Howell A, Hannon RA, Cuzick J, Mackey JR, Beckmann MW, Clack G (2008) Effect of anastrozole on bone mineral density: 5-year results from the anastrozole, tamoxifen, alone or in combination trial 18233230. J Clin Oncol 26:1051–1057

    CAS  PubMed  Article  Google Scholar 

  16. 16.

    Fisher B, Costantino JP, Wickerham DL, Cecchini RS, Cronin WM, Robidoux A, Bevers TB, Kavanah MT, Atkins JN, Margolese RG, Runowicz CD, James JM, Ford LG, Wolmark N (2005) Tamoxifen for the prevention of breast cancer: current status of the National Surgical Adjuvant Breast and Bowel Project P-1 study. J Natl Cancer Inst 97:1652–1662

    CAS  PubMed  Article  Google Scholar 

  17. 17.

    Brufsky AM (2008) Cancer treatment-induced bone loss: pathophysiology and clinical perspectives. Oncologist 13:187e95

    Google Scholar 

  18. 18.

    Shapiro CL, Manola J, Leboff M (2001) Ovarian failure after adjuvant chemotherapy is associated with rapid bone loss in women with early-stage breast cancer. J Clin Oncol Off J Am Soc Clin Oncol 19:3306e11

    Article  Google Scholar 

  19. 19.

    Kanis JA, McCloskey EV, Powles T, Paterson AH, Ashley S, Spector T (1999) A high incidence of vertebral fracture in women with breast cancer. Br J Cancer 79:1179e81

    Article  Google Scholar 

  20. 20.

    Gnant M, Pfeiler G, Dubsky PC, Hubalek M, Greil R, Jakesz R, Wette V, Balic M, Haslbauer F, Melbinger E, Bjelic-Radisic V, Artner-Matuschek S, Fitzal F, Marth C, Sevelda P, Mlineritsch B, Steger GG, Manfreda D, Exner R, Egle D, Bergh J, Kainberger F, Talbot S, Warner D, Fesl C, Singer CF (2015) Austrian Breast and Colorectal Cancer Study Group. Adjuvant denosumab in breast cancer (ABCSG-18): a multicentre, randomised, double-blind, placebo-controlled trial. Lancet. 386(9992):433–443

    CAS  PubMed  Article  Google Scholar 

  21. 21.

    Hadji P, Coleman RE, Wilson C, Powles TJ, Clézardin P, Aapro M, Costa L, Body JJ, Markopoulos C, Santini D, Diel I, Di Leo A, Cameron D, Dodwell D, Smith I, Gnant M, Gray R, Harbeck N, Thurlimann B, Untch M, Cortes J, Martin M, Albert US, Conte PF, Ejlertsen B, Bergh J, Kaufmann M, Holen I (2016) Adjuvant bisphosphonates in early breast cancer: consensus guidance for clinical practice from a European Panel. Ann Oncol 27:379–390

    CAS  PubMed  Article  Google Scholar 

  22. 22.

    FRAX. Fracture risk assessment tool. https://www.sheffield.ac.uk/FRAX/tool.aspx?country=9 (last accessed on 22 June 2019)

  23. 23.

    Rachner TD, Coleman R, Hadji P, Hofbauer LC (2018) Bone health during endocrine therapy for cancer. Lancet Diabetes Endocrinol 6:901–910

    CAS  PubMed  Article  Google Scholar 

  24. 24.

    Defeudis G (2017) The importance of evaluating body composition with dual-energy X-ray absorptiometry in men: the Structure of the Aging Men’s Bones (STRAMBO) study. J Clin Densitom 20:462–463

    PubMed  Article  Google Scholar 

  25. 25.

    Eastell R, Rosen CJ, Black DM, Cheung AM, Murad MH, Shoback D (2019) Pharmacological management of osteoporosis in postmenopausal women: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 104:1595–1622

    PubMed  Article  Google Scholar 

  26. 26.

    Saarto T, Vehmanen L, Elomaa I, Välimäki M, Mäkelä P, Blomqvist C (2001) The effect of clodronate and antioestrogens on bone loss associated with oestrogen withdrawal in postmenopausal women with breast cancer. Br J Cancer 84:1047–1051

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  27. 27.

    Confavreux CB, Fontana A, Guastalla JP, Munoz F, Brun J, Delmas PD (2007) Estrogen-dependent increase in bone turnover and bone loss in postmenopausal women with breast cancer treated with anastrozole. Prevention with bisphosphonates. Bone. 41:346–352

    CAS  PubMed  Article  Google Scholar 

  28. 28.

    Lester JE, Dodwell D, Purohit OP, Gutcher SA, Ellis SP, Thorpe R, Horsman JM, Brown JE, Hannon RA, Coleman RE (2008) Prevention of anastrozole-induced bone loss with monthly oral ibandronate during adjuvant aromatase inhibitor therapy for breast cancer. Clin Cancer Res 14:6336–6342

    CAS  PubMed  Article  Google Scholar 

  29. 29.

    Hines SL, Mincey BA, Sloan JA, Thomas SP, Chottiner E, Loprinzi CL, Carlson MD, Atherton PJ, Salim M, Perez EA (2009) Phase III randomized, placebo-controlled, double-blind trial of risedronate for the prevention of bone loss in premenopausal women undergoing chemotherapy for primary breast cancer. J Clin Oncol 27:1047–1053

    CAS  PubMed  Article  Google Scholar 

  30. 30.

    Van Poznak C, Hannon RA, Mackey JR, Campone M, Apffelstaedt JP, Clack G, Barlow D, Makris A, Eastell R (2010) Prevention of aromatase inhibitor-induced bone loss using risedronate: the SABRE trial. J Clin Oncol 28:967–975

    PubMed  Article  CAS  Google Scholar 

  31. 31.

    Markopoulos C, Tzoracoleftherakis E, Polychronis A, Venizelos B, Dafni U, Xepapadakis G, Papadiamantis J, Zobolas V, Misitzis J, Kalogerakos K, Sarantopoulou A, Siasos N, Koukouras D, Antonopoulou Z, Lazarou S, Gogas H (2010) Management of anastrozole-induced bone loss in breast cancer patients with oral risedronate: results from the ARBI prospective clinical trial. Breast Cancer Res 12:R24

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  32. 32.

    Sestak I, Singh S, Cuzick J, Blake GM, Patel R, Gossiel F, Coleman R, Dowsett M, Forbes JF, Howell A, Eastell R (2014) Changes in bone mineral density at 3 years in postmenopausal women receiving anastrozole and risedronate in the IBIS-II bone substudy: an international, double-blind, randomised, placebo-controlled trial. Lancet Oncol 15:1460–1468

    CAS  PubMed  Article  Google Scholar 

  33. 33.

    Brufsky A, Harker WG, Beck JT, Carroll R, Tan-Chiu E, Seidler C, Hohneker J, Lacerna L, Petrone S, Perez EA (2007) Zoledronic acid inhibits adjuvant letrozole-induced bone loss in postmenopausal women with early breast cancer. J Clin Oncol 25:829–836

    CAS  PubMed  Article  Google Scholar 

  34. 34.

    Bundred NJ, Campbell ID, Davidson N, DeBoer RH, Eidtmann H, Monnier A, Neven P, von Minckwitz G, Miller JC, Schenk NL, Coleman RE (2008) 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. 112:1001–1010

    CAS  PubMed  Article  Google Scholar 

  35. 35.

    Eidtmann H, de Boer R, Bundred N, Llombart-Cussac A, Davidson N, Neven P, von Minckwitz G, Miller J, Schenk N, Coleman R (2010) Efficacy of zoledronic acid in postmenopausal women with early breast cancer receiving adjuvant letrozole: 36-month results of the ZO-FAST study. Ann Oncol 21:2188–2194

    CAS  PubMed  Article  Google Scholar 

  36. 36.

    Brufsky AM, Harker WG, Beck JT, Bosserman L, Vogel C, Seidler C, Jin L, Warsi G, Argonza-Aviles E, Hohneker J, Ericson SG, Perez EA (2012) Final 5-year results of Z-FAST trial: adjuvant zoledronic acid maintains bone mass in postmenopausal breast cancer patients receiving letrozole. Cancer. 118:1192–1201

    CAS  PubMed  Article  Google Scholar 

  37. 37.

    Llombart A, Frassoldati A, Paija O, Sleeboom HP, Jerusalem G, Mebis J, Deleu I, Miller J, Schenk N, Neven P (2012) 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 12:40–48

    CAS  PubMed  Article  Google Scholar 

  38. 38.

    Coleman R, de Boer R, Eidtmann H, Llombart A, Davidson N, Neven P, von Minckwitz G, Sleeboom HP, Forbes J, Barrios C, Frassoldati A, Campbell I, Paija O, Martin N, Modi A, Bundred N (2013) Zoledronic acid (zoledronate) for postmenopausal women with early breast cancer receiving adjuvant letrozole (ZO-FAST study): final 60-month results. Ann Oncol 24:398–405

    CAS  PubMed  Article  Google Scholar 

  39. 39.

    Wagner-Johnston ND, Sloan JA, Liu H, Kearns AE, Hines SL, Puttabasavaiah S, Dakhil SR, Lafky JM, Perez EA, Loprinzi CL (2015) 5-year follow-up of a randomized controlled trial of immediate versus delayed zoledronic acid for the prevention of bone loss in postmenopausal women with breast cancer starting letrozole after tamoxifen: N03CC (Alliance) trial. Cancer. 121:2537–2543

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  40. 40.

    Gnant M, Mlineritsch B, Luschin-Ebengreuth G, Kainberger F, Kässmann H, Piswanger-Sölkner JC, Seifert M, Ploner F, Menzel C, Dubsky P, Fitzal F, Bjelic-Radisic V, Steger G, Greil R, Marth C, Kubista E, Samonigg H, Wohlmuth P, Mittlböck M, Jakesz R (2008) Austrian Breast and Colorectal Cancer Study Group (ABCSG). 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 9:840–849

    CAS  PubMed  Article  Google Scholar 

  41. 41.

    Gnant M, Mlineritsch B, Stoeger H, Luschin-Ebengreuth G, Knauer M, Moik M, Jakesz R, Seifert M, Taucher S, Bjelic-Radisic V, Balic M, Eidtmann H, Eiermann W, Steger G, Kwasny W, Dubsky P, Selim U, Fitzal F, Hochreiner G, Wette V, Sevelda P, Ploner F, Bartsch R, Fesl C, Greil R (2015) Austrian Breast and Colorectal Cancer Study Group, Vienna, Austria. Zoledronic acid combined with adjuvant endocrine therapy of tamoxifen versus anastrozol plus ovarian function suppression in premenopausal early breast cancer: final analysis of the Austrian Breast and Colorectal Cancer Study Group Trial 12. Ann Oncol 26:313–320

    CAS  PubMed  Article  Google Scholar 

  42. 42.

    Hadji P, Kauka A, Ziller M, Birkholz K, Baier M, Muth M, Bauer M (2014) Effects of zoledronic acid on bone mineral density in premenopausal women receiving neoadjuvant or adjuvant therapies for HR+ breast cancer: the ProBONE II study. Osteoporos Int 25:1369–1378

    CAS  PubMed  Article  Google Scholar 

  43. 43.

    Kalder M, Kyvernitakis I, Albert US, Baier-Ebert M, Hadji P (2015) Effects of zoledronic acid versus placebo on bone mineral density and bone texture analysis assessed by the trabecular bone score in premenopausal women with breast cancer treatment-induced bone loss: results of the ProBONE II substudy. Osteoporos Int 26:353–360

    CAS  PubMed  Article  Google Scholar 

  44. 44.

    Hadji P, Aapro MS, Body JJ, Gnant M, Brandi ML, Reginster JY, Zillikens MC, Glüer CC, de Villiers T, Baber R, Roodman GD, Cooper C, Langdahl B, Palacios S, Kanis J, Al-Daghri N, Nogues X, Eriksen EF, Kurth A, Rizzoli R, Coleman RE (2017) Management of Aromatase Inhibitor-Associated Bone Loss (AIBL) in postmenopausal women with hormone sensitive breast cancer: joint position statement of the IOF, CABS, ECTS, IEG, ESCEO IMS, and SIOG. J Bone Oncol 7:1–12

    PubMed  PubMed Central  Article  Google Scholar 

  45. 45.

    Ellis GK, Bone HG, Chlebowski R, Paul D, Spadafora S, Fan M, Kim D (2009) Effect of denosumab on bone mineral density in women receiving adjuvant aromatase inhibitors for non-metastatic breast cancer: subgroup analyses of a phase 3 study. Breast Cancer Res Treat 118(1):81–87

    CAS  PubMed  Article  Google Scholar 

  46. 46.

    Tsourdi E, Langdahl B, Cohen-Solal M, Aubry-Rozier B, Eriksen EF, Guañabens N, Obermayer-Pietsch B, Ralston SH, Eastell R, Zillikens MC (2017) Discontinuation of denosumab therapy for osteoporosis: a systematic review and position statement by ECTS. Bone. 105:11–17

    PubMed  Article  Google Scholar 

  47. 47.

    Anastasilakis AD, Polyzos SA, Makras P, Aubry-Rozier B, Kaouri S, Lamy O (2017) Clinical features of 24 patients with rebound-associated vertebral fractures after denosumab discontinuation: systematic review and additional cases. J Bone Miner Res 32:1291–1296

    CAS  PubMed  Article  Google Scholar 

  48. 48.

    Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) (2015) Adjuvant bisphosphonate treatment in early breast cancer: meta-analyses of individual patient data from randomized trials. Lancet 386:1353–1361

    Article  CAS  Google Scholar 

  49. 49.

    Gnant M, Pfeiler G, Steger GG, Egle D, Greil R, Fitzal F, Wette V, Balic M, Haslbauer F, Melbinger-Zeinitzer E, Bjelic-Radisic V, Jakesz R, Marth C, Sevelda P, Mlineritsch B, Exner R, Fesl C, Frantal S, Singer CF (2019) Austrian Breast and Colorectal Cancer Study Group. Adjuvant denosumab in postmenopausal patients with hormone receptor-positive breast cancer (ABCSG-18): disease-free survival results from a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol 20:339–351

    CAS  PubMed  Article  Google Scholar 

  50. 50.

    Marsden J, British Menopause Society (2019) British Menopause Society consensus statement: the risks and benefits of HRT before and after a breast cancer diagnosis. Post Reprod Health 25:33–37

    PubMed  Article  Google Scholar 

  51. 51.

    Kenemans P, Bundred NJ, Foidart JM, Kubista E, von Schoultz B, Sismondi P, Vassilopoulou-Sellin R, Yip CH, Egberts J, Mol-Arts M, Mulder R, van Os S, Beckmann MW, LIBERATE Study Group (2009) Safety and efficacy of tibolone in breast-cancer patients with vasomotor symptoms: a double-blind, randomised, non-inferiority trial. Lancet Oncol 10:135–146

    CAS  PubMed  Article  Google Scholar 

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Correspondence to Irene Lambrinoudaki.

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The original version of this article was revised: In the original version the name Stavroula Α. Paschou was written with a Greek alpha. The correct author name reads as follows: Stavroula A. Paschou

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Paschou, S.A., Augoulea, A. & Lambrinoudaki, I. Bone health care in women with breast cancer. Hormones 19, 171–178 (2020). https://doi.org/10.1007/s42000-019-00164-y

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Keywords

  • Breast cancer
  • Survivors
  • Aromatase inhibitors
  • Tamoxifen
  • Bone
  • BMD
  • Bisphosphonates
  • Denosumab
  • MHT