Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
BMC Cancer
Published in: BMC Cancer 1/2011

Open Access 01-12-2011 | Review

Increased fracture rate in women with breast cancer: a review of the hidden risk

Author: Jean-Jacques Body

Published in: BMC Cancer | Issue 1/2011

Login to get access

Abstract

Background

Women with breast cancer, particularly individuals diagnosed at a relatively early age, have an increased incidence of fractures. Fractures can have serious clinical consequences including the need for major surgery, increased morbidity and mortality, increased cost of disease management, and reduced quality of life for patients. The primary cause of the increased fracture risk appears to be an accelerated decrease in bone mineral density (BMD) resulting from the loss of estrogenic signaling that occurs with most treatments for breast cancer, including aromatase inhibitors. However, factors other than BMD levels alone may influence treatment decisions to reduce fracture risk in this setting. Our purpose is to review current evidence for BMD loss and fracture risk during treatment for breast cancer and discuss pharmacologic means to reduce this risk.

Results

Fracture risk during treatment for breast cancer may be influenced by the rate of BMD loss and the consequent rapid alterations in bone microarchitecture, in addition to the established fracture risk factors in postmenopausal osteoporosis. The rapid decrease in BMD during adjuvant chemoendocrine therapy for breast cancer may necessitate more aggressive pharmacotherapy than is indicated for healthy postmenopausal women who develop osteoporosis. Over the last few years, clinical trials have established the effectiveness of bisphosphonates and other antiresorptive agents to preserve BMD during adjuvant therapy for early breast cancer. In addition, some bisphosphonates (eg, zoledronic acid) may also delay disease recurrence in women with hormone-responsive tumors, thereby providing an adjuvant benefit in addition to preserving BMD and potentially preventing fractures.

Conclusions

It is likely that a combined fracture risk assessment (eg, as in the WHO FRAX algorithm) will more accurately identify both women with postmenopausal osteoporosis and women with breast cancer who require bone-protective therapy.
Appendix
Available only for authorised users
Literature
1.
Kanis JA, McCloskey EV, Powles T, Paterson AHG, Ashley S, Spector T: A high incidence of vertebral fracture in women with breast cancer. Br J Cancer. 1999, 79: 1179-1181. 10.1038/sj.bjc.6690188.CrossRefPubMedPubMedCentral
2.
McCloskey EV, Beneton M, Charlesworth D, Kayan K, deTakats D, Dey A, Orgee J, Ashford R, Forster M, Cliffe J, Kersh L, Brazier J, Nichol J, Aropuu S, Jalava T, Kanis JA: Clodronate reduces the incidence of fractures in community-dwelling elderly women unselected for osteoporosis: results of a double-blind, placebo-controlled randomized study. J Bone Miner Res. 2007, 22: 135-141.CrossRefPubMed
3.
Saarto T, Blomqvist C, Valimaki M, Makela P, Sarna S, Elomaa I: Clodronate improves bone mineral density in post-menopausal breast cancer patients treated with adjuvant antioestrogens. Br J Cancer. 1997, 75: 602-605. 10.1038/bjc.1997.105.CrossRefPubMedPubMedCentral
4.
Chen Z, Maricic M, Bassford TL, Pettinger M, Ritenbaugh C, Lopez AM, Barad DH, Gass M, Leboff MS: Fracture risk among breast cancer survivors: results from the Women's Health Initiative Observational Study. Arch Intern Med. 2005, 165: 552-558. 10.1001/archinte.165.5.552.CrossRefPubMed
5.
Coleman RE, Banks LM, Girgis SI, Vrdoljak E, Fox J, Cawthorn SJ, Patel A, Bliss JM, Coombes RC, Kilburn LS: Reversal of skeletal effects of endocrine treatments in the Intergroup Exemestane Study. Breast Cancer Res Treat. 2010, 124: 153-161. 10.1007/s10549-010-1121-7.CrossRefPubMed
6.
Cuzick J, Sestak I, Baum M, Buzdar A, Howell A, Dowsett M, Forbes JF: Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 10-year analysis of the ATAC trial. Lancet Oncol. 2010, 11: 1135-1141. 10.1016/S1470-2045(10)70257-6.CrossRefPubMed
7.
Rabaglio M, Sun Z, Price KN, Castiglione-Gertsch M, Hawle H, Thurlimann B, Mouridsen H, Campone M, Forbes JF, Paridaens RJ, Colleoni M, Pienkowski T, Nogaret JM, Lang I, Smith I, Gelber RD, Goldhirsch A, Coates AS: Bone fractures among postmenopausal patients with endocrine-responsive early breast cancer treated with 5 years of letrozole or tamoxifen in the BIG 1-98 trial. Ann Oncol. 2009, 20: 1489-1498. 10.1093/annonc/mdp033.CrossRefPubMedPubMedCentral
8.
Hadji P: Aromatase inhibitor-associated bone loss in breast cancer patients is distinct from postmenopausal osteoporosis. Crit Rev Oncol Hematol. 2009, 69: 73-82. 10.1016/j.critrevonc.2008.07.013.CrossRefPubMed
9.
Cummings SR, Browner WS, Bauer D, Stone K, Ensrud K, Jamal S, Ettinger B: Endogenous hormones and the risk of hip and vertebral fractures among older women. N Engl J Med. 1998, 339: 733-738. 10.1056/NEJM199809103391104.CrossRefPubMed
10.
MacLaughlin EJ, Sleeper RB, McNatty D, Raehl CL: Management of age-related osteoporosis and prevention of associated fractures. Ther Clin Risk Manag. 2006, 2: 281-295. 10.2147/tcrm.2006.2.3.281.CrossRefPubMedPubMedCentral
11.
Schurch MA, Rizzoli R, Mermillod B, Vasey H, Michel JP, Bonjour JP: A prospective study on socioeconomic aspects of fracture of the proximal femur. J Bone Miner Res. 1996, 11: 1935-1942.CrossRefPubMed
12.
Anand S, Buch K: Post-discharge symptomatic thromboembolic events in hip fracture patients. Ann R Coll Surg Engl. 2007, 89: 517-520. 10.1308/003588407X202065.CrossRefPubMedPubMedCentral
13.
Nakase J, Toribatake Y, Mouri Y, Seki H, Kitaoka K, Tomita K: Heparin versus danaproid for prevention of venous thromboembolism after hip surgery. J Orthop Surg (Hong Kong). 2009, 17: 6-9.
14.
Margolis DJ, Knauss J, Bilker W, Baumgarten M: Medical conditions as risk factors for pressure ulcers in an outpatient setting. Age Ageing. 2003, 32: 259-264. 10.1093/ageing/32.3.259.CrossRefPubMed
15.
Schlaich C, Minne HW, Bruckner T, Wagner G, Gebest HJ, Grunze M, Ziegler R, Leidig-Bruckner G: Reduced pulmonary function in patients with spinal osteoporotic fractures. Osteoporos Int. 1998, 8: 261-267. 10.1007/s001980050063.CrossRefPubMed
16.
Guise TA: Bone loss and fracture risk associated with cancer therapy. Oncologist. 2006, 11: 1121-1131. 10.1634/theoncologist.11-10-1121.CrossRefPubMed
17.
Coleman RE, Banks LM, Girgis SI, Kilburn LS, Vrdoljak E, Fox J, Cawthorn SJ, Patel A, Snowdon CF, Hall E, Bliss JM, Coombes RC: 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. 2007, 8: 119-127. 10.1016/S1470-2045(07)70003-7.CrossRefPubMed
18.
Howell A, Cuzick J, Baum M, Buzdar A, Dowsett M, Forbes JF, Hoctin-Boes G, Houghton J, Locker GY, Tobias JS: Results of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial after completion of 5 years' adjuvant treatment for breast cancer. Lancet. 2005, 365: 60-62.CrossRefPubMed
19.
Salaffi F, Cimmino MA, Malavolta N, Carotti M, Di Matteo L, Scendoni P, Grassi W: The burden of prevalent fractures on health-related quality of life in postmenopausal women with osteoporosis: the IMOF study. J Rheumatol. 2007, 34: 1551-1560.PubMed
20.
Bliuc D, Nguyen ND, Milch VE, Nguyen TV, Eisman JA, Center JR: Mortality risk associated with low-trauma osteoporotic fracture and subsequent fracture in men and women. JAMA. 2009, 301: 513-521. 10.1001/jama.2009.50.CrossRefPubMed
21.
Maxwell C, Viale PH: Cancer treatment-induced bone loss in patients with breast or prostate cancer. Oncol Nurs Forum. 2005, 32: 589-603. 10.1188/05.ONF.589-603.CrossRefPubMed
22.
Hadji P, Body JJ, Aapro M, Brufsky A, Coleman R, Guise T, Lipton A, Tubiana-Hulin M: Practical guidance for the management of aromatase inhibitor-associated bone loss. Ann Oncol. 2008, 19: 1407-1416. 10.1093/annonc/mdn164.CrossRefPubMed
23.
Pierce SM, Recht A, Lingos TI, Abner A, Vicini F, Silver B, Herzog A, Harris JR: Long-term radiation complications following conservative surgery (CS) and radiation therapy (RT) in patients with early stage breast cancer. Int J Radiat Oncol Biol Phys. 1992, 23: 915-923. 10.1016/0360-3016(92)90895-O.CrossRefPubMed
24.
Bruning PF, Pit MJ, de Jong-Bakker M, van den Ende A, Hart A, van Enk A: Bone mineral density after adjuvant chemotherapy for premenopausal breast cancer. Br J Cancer. 1990, 61: 308-310. 10.1038/bjc.1990.58.CrossRefPubMedPubMedCentral
25.
Gnant MFX, Mlineritsch B, Luschin-Ebengreuth G, Grampp S, Kaessmann H, Schmid M, Menzel C, Piswanger-Soelkner JC, Galid A, Mittlboeck M, Hausmaninger H, Jakesz R: Zoledronic acid prevents cancer treatment-induced bone loss in premenopausal women receiving adjuvant endocrine therapy for hormone-responsive breast cancer: a report from the Austrian Breast and Colorectal Cancer Study Group. J Clin Oncol. 2007, 25: 820-828. 10.1200/JCO.2005.02.7102.CrossRefPubMed
26.
Steinbuch M, Youket TE, Cohen S: Oral glucocorticoid use is associated with an increased risk of fracture. Osteoporos Int. 2004, 15: 323-328. 10.1007/s00198-003-1548-3.CrossRefPubMed
27.
28.
Hillner BE, Ingle JN, Chlebowski RT, Gralow J, Yee GC, Janjan NA, Cauley JA, Blumenstein BA, Albain KS, Lipton A, Brown S: American Society of Clinical Oncology 2003 update on the role of bisphosphonates and bone health issues in women with breast cancer. J Clin Oncol. 2003, 21: 4042-4057. 10.1200/JCO.2003.08.017.CrossRefPubMed
29.
World Health Organization: Prevention and Management of Osteoporosis. Technical Report Series 921. 2003, Geneva, Switzerland: World Health Organization
30.
Body JJ, Bergmann P, Boonen S, Boutsen Y, Devogelaer JP, Goemaere S, Reginster JY, Rozenberg S, Kaufman JM: Management of cancer treatment-induced bone loss in early breast and prostate cancer - a consensus paper of the Belgian Bone Club. Osteoporos Int. 2007, 18: 1439-1450. 10.1007/s00198-007-0439-4.CrossRefPubMed
31.
Kanis JA, Johnell O, Oden A, Dawson A, De Laet C, Jonsson B: Ten year probabilities of osteoporotic fractures according to BMD and diagnostic thresholds. Osteoporos Int. 2001, 12: 989-995. 10.1007/s001980170006.CrossRefPubMed
32.
Delmas PD, Fontana A: Bone loss induced by cancer treatment and its management. Eur J Cancer. 1998, 34: 260-262. 10.1016/S0959-8049(97)10135-6.CrossRefPubMed
33.
Thurlimann B, Keshaviah A, Coates AS, Mouridsen H, Mauriac L, Forbes JF, Paridaens R, Castiglione-Gertsch M, Gelber RD, Rabaglio M, Smith I, Wardley A, Price KN, Goldhirsch A: A comparison of letrozole and tamoxifen in postmenopausal women with early breast cancer. The Breast International Group (BIG) 1-98 Collaborative Group. N Engl J Med. 2005, 353: 2747-2757.CrossRefPubMed
34.
Lindsey R, Christiansen C, Einhorn TA, McKay Hart D, Ljunghall S, Mautalen CA, Meunier PJ, Morii H, Mundy GR, Rapado A, Stevenson J: Consensus development statement: who are candidates for prevention and treatment for osteoporosis?. Osteoporos Int. 1997, 7: 1-6.
35.
Lappe JM, Tinley ST: Prevention of osteoporosis in women treated for hereditary breast and ovarian carcinoma: a need that is overlooked. Cancer. 1998, 83: 830-834. 10.1002/(SICI)1097-0142(19980901)83:5<830::AID-CNCR2>3.0.CO;2-M.CrossRefPubMed
36.
Fogelman I, Blake GM, Blamey R, Palmer M, Sauerbrei W, Schumacher M, Serin D, Stewart A, Wilpshaar W: Bone mineral density in premenopausal women treated for node-positive early breast cancer with 2 years of goserelin or 6 months of cyclophosphamide, methotrexate and 5-fluorouracil (CMF). Osteoporos Int. 2003, 14: 1001-1006. 10.1007/s00198-003-1508-y.CrossRefPubMed
37.
Dowsett M: Future uses for aromatase inhibitors in breast cancer. J Steroid Biochem Mol Biol. 1997, 61: 261-266. 10.1016/S0960-0760(97)80021-0.CrossRefPubMed
38.
Eastell R, Hannon RA, Cuzick J, Dowsett M, Clack G, Adams JE: 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. 2006, 21: 1215-1223. 10.1359/jbmr.060508.CrossRefPubMed
39.
Lester JE, Dodwell D, Purohit OP, Gutcher SA, Ellis SP, Thorpe R, Horsman JM, Brown JE, Hannon RA, Coleman RE: Prevention of anastrozole-induced bone loss with monthly oral ibandronate during adjuvant aromatase inhibitor therapy for breast cancer. Clin Cancer Res. 2008, 14: 6336-6342. 10.1158/1078-0432.CCR-07-5101.CrossRefPubMed
40.
Van Poznak C, Hannon RA, Mackey JR, Campone M, Apffelstaedt JP, Clack G, Barlow D, Makris A, Eastell R: Prevention of aromatase inhibitor-induced bone loss using risedronate: the SABRE trial. J Clin Oncol. 2010, 28: 967-975. 10.1200/JCO.2009.24.5902.CrossRefPubMed
41.
Ellis GK, Bone HG, Chlebowski R, Paul D, Spadafora S, Smith J, Fan M, Jun S: Randomized trial of denosumab in patients receiving adjuvant aromatase inhibitors for nonmetastatic breast cancer. J Clin Oncol. 2008, 26: 4875-4882. 10.1200/JCO.2008.16.3832.CrossRefPubMed
42.
Brufsky AM, Bosserman LD, Caradonna RR, Haley BB, Jones CM, Moore HC, Jin L, Warsi GM, Ericson SG, Perez EA: 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: 77-85. 10.3816/CBC.2009.n.015.CrossRefPubMed
43.
Llombart A: Zoledronic acid in the prevention of aromatase inhibitor-associated bone loss in postmenopausal women receiving letrozole as adjuvant therapy for early breast cancer (E-ZO-FAST trial). 14th European Cancer Conference (ECCO): 23-27. 2007, Barcelona, Spain, Abstract 2008, September
44.
Eidtmann H, de Boer R, Bundred N, Llombart-Cussac A, Davidson N, Neven P, von Minckwitz G, Miller J, Schenk N, Coleman R: 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: 2188-2194. 10.1093/annonc/mdq217.CrossRefPubMed
45.
Gnant M, Mlineritsch B, Schippinger W, Luschin-Ebengreuth G, Postlberger S, Menzel C, Jakesz R, Seifert M, Hubalek M, Bjelic-Radisic V, Samonigg H, Tausch C, Eidtmann H, Steger G, Kwasny W, Dubsky P, Fridrik M, Fitzal F, Stierer M, Rucklinger E, Greil R, Marth C: Endocrine therapy plus zoledronic acid in premenopausal breast cancer. N Engl J Med. 2009, 360: 679-691. 10.1056/NEJMoa0806285.CrossRefPubMed
46.
Coleman RE, Thorpe HC, Cameron D, Didwell D, Burkinshaw R, Keane M, Gil M, Houston SJ, Grieve RJ, Barrett-Lee PJ, Ritchie D, Davies C, Bell R: Adjuvant treatment with zoledronic acid in stage II/III breast cancer: the AZURE trial (BIG 01/04). 33rd Annual San Antonio Breast Cancer Symposium: 8-12. 2010, Abstract S4-5, December ; San Antonio, TX
47.
Siris ES, Chen Y-T, Abbott TA, Barrett-Connor E, Miller PD, Wehren LE, Berger ML: Bone mineral density thresholds for pharmacological intervention to prevent fractures. Arch Intern Med. 2004, 164: 1108-1112. 10.1001/archinte.164.10.1108.CrossRefPubMed
48.
Seeman E, Delmas PD: Bone quality -- the material and structural basis of bone strength and fragility. N Engl J Med. 2006, 354: 2250-2261. 10.1056/NEJMra053077.CrossRefPubMed
49.
50.
Lewiecki EM: Managing osteoporosis: challenges and strategies. Cleve Clin J Med. 2009, 76: 457-466. 10.3949/ccjm.76a.09019.CrossRefPubMed
51.
Reid DM, Doughty J, Eastell R, Heys SD, Howell A, McCloskey EV, Powles T, Selby P, Coleman RE: Guidance for the management of breast cancer treatment-induced bone loss: a consensus position statement from a UK Expert Group. Cancer Treat Rev. 2008, 34 (Suppl 1): S3-18.CrossRefPubMed
52.
Hadji P, Aapro MS, Body JJ, Bundred NJ, Brufsky A, Coleman RE, Gnant M, Guise T, Lipton A: Management of aromatase inhibitor-associated bone loss in postmenopausal women with breast cancer: practical guidance for prevention and treatment. Ann Oncol. 2011
53.
Kanis JA, Oden A, Johnell O, Johansson H, De Laet C, Brown J, Burckhardt P, Cooper C, Christiansen C, Cummings S, Eisman JA, Fujiwara S, Gluer C, Goltzman D, Hans D, Krieg MA, La Croix A, McCloskey E, Mellstrom D, Melton LJ, Pols H, Reeve J, Sanders K, Schott AM, Silman A, Torgerson D, van Staa T, Watts NB, Yoshimura N: The use of clinical risk factors enhances the performance of BMD in the prediction of hip and osteoporotic fractures in men and women. Osteoporos Int. 2007, 18: 1033-1046. 10.1007/s00198-007-0343-y.CrossRefPubMed
54.
Lipton A: Should bisphosphonates be utilized in the adjuvant setting for breast cancer?. Breast Cancer Res Treat. 2010, 122: 627-636. 10.1007/s10549-010-0935-7.CrossRefPubMed
Metadata
Title
Increased fracture rate in women with breast cancer: a review of the hidden risk
Author
Jean-Jacques Body
Publication date
01-12-2011
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2011
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-11-384

Other articles of this Issue 1/2011

BMC Cancer 1/2011 Go to the issue

Research article

Survival endpoints in colorectal cancer and the effect of second primary other cancer on disease free survival

Research article

Effects of EpCAM overexpression on human breast cancer cell lines

Research article

Literature survey on epidemiology and pathology of gangliocytic paraganglioma

Review

Renal cell cancer among African Americans: an epidemiologic review

Research article

The impact of audit and feedback on nodal harvest in colorectal cancer

Research article

Can Bcl-XL expression predict the radio sensitivity of Bilharzial-related squamous bladder carcinoma? a prospective comparative study
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits