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Osteoporosis International
Published in: Osteoporosis International 1/2019

01-01-2019 | Original Article

Hormone therapy and osteoporosis in breast cancer survivors: assessment of risk and adherence to screening recommendations

Authors: R. Hamood, H. Hamood, I. Merhasin, L. Keinan-Boker

Published in: Osteoporosis International | Issue 1/2019

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Abstract

Summary

The long-term impact of hormone therapy for breast cancer on risk of osteoporosis and the extent to which bone screening recommendations are implemented in daily practice remain unknown. We found that the aromatase inhibitor-induced risk of osteoporosis did not continue in the off-treatment follow-up. Adherence to screening recommendations was suboptimal.

Introduction

A case-cohort study was undertaken to better understand the impact of hormone therapy on breast cancer patients’ risk of osteoporosis, and to estimate the extent to which current bone mineral density screening recommendations are implemented in real-life daily practice.

Methods

This study is based on 1692 female breast cancer survivors recruited from “Leumit” healthcare fund, who were diagnosed with primary nonmetastatic invasive breast cancer between 2002 and 2012. A 20% random subcohort was sampled at baseline, and all osteoporosis cases were identified. Adjusted hazard ratios (HR) with 95% confidence intervals (CI) were estimated by weighted Cox proportional hazards models.

Results

Of 1692 breast cancer survivors, 312 developed osteoporosis during a median follow-up of 5 years. The crude cumulative incidence of osteoporosis accounting for death as a competing risk was 25.7% (95% CI, 21.9–29.5%). In multivariable analyses, osteoporosis was positively associated with the aromatase inhibitor (AI) sequential treatment after tamoxifen (HR, 3.14; 95% CI, 1.44–6.88; P = .004) but was more pronounced with AI use as upfront monotherapy (HR, 5.53; 95% CI, 1.46–20.88; P = .012). This effect did not continue in the off-treatment follow-up. In subgroup analysis by menopausal status, tamoxifen did not seem to confer a protective effect on bone health in postmenopausal patients. Adherence to screening recommendations in AI-treated postmenopausal women was suboptimal, particularly at baseline and after 48 months of continuous AI use.

Conclusions

The natural, age-related reduction in bone density is exacerbated by breast cancer active AI treatment. Future research should focus on investigating screening adherence-related barriers/facilitators and effective strategies to bring practice in line with agreed standards.
Appendix
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Literature
1.
Brennan ME, Houssami N (2011) Overview of long term care of breast cancer survivors. Maturitas 69:106–112PubMedCrossRef
2.
Bell R, Lewis J (2007) Assessing the risk of bone fracture among postmenopausal women who are receiving adjuvant hormonal therapy for breast cancer. Curr Med Res Opin 23:1045–1051PubMedCrossRef
3.
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 7:1–12PubMedPubMedCentralCrossRef
4.
Amir E, Seruga B, Niraula S, Carlsson L, Ocana A (2011) Toxicity of adjuvant endocrine therapy in postmenopausal breast cancer patients: a systematic review and meta-analysis. J Natl Cancer Inst 103:1299–1309PubMedCrossRef
5.
6.
7.
Zekri J, Farag K (2016) Assessment of bone health in breast cancer patients starting adjuvant aromatase inhibitors: a quality improvement clinical audit. J Bone Oncol 5:159–162PubMedPubMedCentralCrossRef
8.
Lindsey AM, Gross G, Twiss J, Waltman N, Ott C, Moore TE (2002) Postmenopausal survivors of breast cancer at risk for osteoporosis: nutritional intake and body size. Cancer Nurs 25:50–56PubMedCrossRef
9.
10.
Cosman F, de Beur SJ, LeBoff MS, Lewiecki EM, Tanner B, Randall S, Lindsay R, National Osteoporosis Foundation (2014) Clinician’s guide to prevention and treatment of osteoporosis. Osteoporos Int 25:2359–2381PubMedPubMedCentralCrossRef
11.
Johnell O, Kanis JA (2006) An estimate of the worldwide prevalence and disability associated with osteoporotic fractures. Osteoporos Int 17:1726–1733CrossRefPubMed
12.
Gralow JR, Biermann JS, Farooki A, et al (2013) NCCN Task Force Report: Bone Health In Cancer Care. J Natl Compr Cancer Netw 11 Suppl 3: S1–50; quiz S51
13.
Body JJ, Terpos E, Tombal B, Hadji P, Arif A, Young A, Aapro M, Coleman R (2016) Bone health in the elderly cancer patient: a SIOG position paper. Cancer Treat Rev 51:46–53PubMedCrossRef
14.
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) American Society of Clinical Oncology 2003 update on the role of bisphosphonates and bone health issues in women with breast cancer. J Clin Oncol 21:4042–4057PubMedCrossRef
15.
Runowicz CD, Leach CR, Henry NL, Henry KS, Mackey HT, Cowens-Alvarado RL, Cannady RS, Pratt-Chapman ML, Edge SB, Jacobs LA, Hurria A, Marks LB, LaMonte SJ, Warner E, Lyman GH, Ganz PA (2016) American Cancer Society/American Society of Clinical Oncology Breast Cancer Survivorship Care Guideline. J Clin Oncol 34:611–635PubMedCrossRef
16.
Stratton J, Hu X, Soulos PR, Davidoff AJ, Pusztai L, Gross CP, Mougalian SS (2017) Bone density screening in postmenopausal women with early-stage breast cancer treated with aromatase inhibitors. J Oncol Pract 13:e505–e515PubMedCrossRef
17.
Tremblay D, Patel V, Fifer KM, Caro J, Kolodka O, Mandelli J, Shapiro CL (2018) Management of bone health in postmenopausal women on aromatase inhibitors (AIs): a single health care system experience. Support Care Cancer 26:197–202PubMedCrossRef
18.
Tremollieres FA (2014) Screening for osteoporosis after breast cancer: for whom, why and when. Maturitas 79:343–348PubMedCrossRef
19.
Eastell R, Adams J, Clack G, Howell A, Cuzick J, Mackey J, Beckmann MW, Coleman RE (2011) Long-term effects of anastrozole on bone mineral density: 7-year results from the ATAC trial. Ann Oncol 22:857–862PubMedCrossRef
20.
Pawloski PA, Geiger AM, Haque R, Kamineni A, Fouayzi H, Ogarek J, Petersen HV, Bosco JLF, Thwin SS, Silliman RA, Field TS (2013) Fracture risk in older, long-term survivors of early-stage breast cancer. J Am Geriatr Soc 61:888–895PubMedPubMedCentralCrossRef
21.
Powles TJ, Hickish T, Kanis JA, Tidy A, Ashley S (1996) Effect of tamoxifen on bone mineral density measured by dual-energy x-ray absorptiometry in healthy premenopausal and postmenopausal women. J Clin Oncol 14:78–84PubMedCrossRef
22.
Barlow WE, Ichikawa L, Rosner D, Izumi S (1999) Analysis of case-cohort designs. J Clin Epidemiol 52:1165–1172PubMedCrossRef
23.
Aday LA (1996) Designing and conducting health surveys: a comprehensive guide. Jossey-Bass Publishers, San Francisco
24.
Hamood R, Hamood H, Merhasin I, Keinan-Boker L (2016) A feasibility study to assess the validity of administrative data sources and self-reported information of breast cancer survivors. Isr J Health Policy Res 5:50PubMedPubMedCentralCrossRef
25.
Hamood R, Hamood H, Merhasin I, Keinan-Boker L (2017) Chronic pain and other symptoms among breast cancer survivors: prevalence, predictors, and effects on quality of life. Breast Cancer Res Treat 167:157–169PubMedCrossRef
26.
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 19:3306–3311PubMedCrossRef
27.
Spangler L, Yu O, Loggers E, Boudreau DM (2013) Bone mineral density screening among women with a history of breast cancer treated with aromatase inhibitors. J Women's Health (Larchmt) 22:132–140CrossRef
28.
Goldshtein I, Chandler J, Shalev V et al (2015) Osteoporosis in the community: findings from a novel computerized registry in a large health organization in Israel. J Aging Res Clin Pract 4:59–65
29.
Gooley TA, Leisenring W, Crowley J, Storer BE (1999) Estimation of failure probabilities in the presence of competing risks: new representations of old estimators. Stat Med 18:695–706PubMedCrossRef
30.
Lipscombe LL, Fischer HD, Yun L, Gruneir A, Austin P, Paszat L, Anderson GM, Rochon PA (2012) Association between tamoxifen treatment and diabetes: a population-based study. Cancer 118:2615–2622PubMedCrossRef
31.
Dowsett M, Haynes BP (2003) Hormonal effects of aromatase inhibitors: focus on premenopausal effects and interaction with tamoxifen. J Steroid Biochem Mol Biol 86:255–263PubMedCrossRef
32.
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 26:1051–1057PubMedCrossRef
33.
Mincey BA, Duh MS, Thomas SK, Moyneur E, Marynchencko M, Boyce SP, Mallett D, Perez EA (2006) Risk of cancer treatment-associated bone loss and fractures among women with breast cancer receiving aromatase inhibitors. Clin Breast Cancer 7:127–132PubMedCrossRef
34.
Perez EA, Josse RG, Pritchard KI, Ingle JN, Martino S, Findlay BP, Shenkier TN, Tozer RG, Palmer MJ, Shepherd LE, Liu S, Tu D, Goss PE (2006) Effect of letrozole versus placebo on bone mineral density in women with primary breast cancer completing 5 or more years of adjuvant tamoxifen: a companion study to NCIC CTG MA.17. J Clin Oncol 24:3629–3635PubMedCrossRef
35.
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 25:829–836PubMedCrossRef
36.
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 21:2188–2194PubMedCrossRef
37.
Conte P, Frassoldati A (2007) Aromatase inhibitors in the adjuvant treatment of postmenopausal women with early breast cancer: putting safety issues into perspective. Breast J 13:28–35PubMedCrossRef
38.
Twiss JJ, Waltman N, Ott CD, Gross GJ, Lindsey AM, Moore TE (2001) Bone mineral density in postmenopausal breast cancer survivors. J Am Acad Nurse Pract 13:276–284PubMedCrossRef
39.
Ding H, Field TS (2007) Bone health in postmenopausal women with early breast cancer: how protective is tamoxifen? Cancer Treat Rev 33:506–513PubMedCrossRef
40.
Eastell R, Hannon R (2005) Long-term effects of aromatase inhibitors on bone. J Steroid Biochem Mol Biol 95:151–154PubMedCrossRef
41.
Cooke AL, Metge C, Lix L, Prior HJ, Leslie WD (2008) Tamoxifen use and osteoporotic fracture risk: a population-based analysis. J Clin Oncol 26:5227–5232PubMedCrossRef
42.
Lewiecki EM (2005) Review of guidelines for bone mineral density testing and treatment of osteoporosis. Curr Osteoporos Rep 3:75–83PubMedCrossRef
43.
Hewitt M, Greenfield S, Stovall E (2006) From cancer patient to cancer survivor: lost in transition. the National Academies Press, Washington DC
44.
Gregson CL, Hardcastle SA, Cooper C, Tobias JH (2013) Friend or foe: high bone mineral density on routine bone density scanning, a review of causes and management. Rheumatology (Oxford) 52:968–985CrossRef
45.
Kanis JA, Oden A, Johansson H, Borgstrom F, Strom O, McCloskey E (2009) FRAX and its applications to clinical practice. Bone 44:734–743PubMedCrossRef
Metadata
Title
Hormone therapy and osteoporosis in breast cancer survivors: assessment of risk and adherence to screening recommendations
Authors
R. Hamood
H. Hamood
I. Merhasin
L. Keinan-Boker
Publication date
01-01-2019
Publisher
Springer London
Published in
Osteoporosis International / Issue 1/2019
Print ISSN: 0937-941X
Electronic ISSN: 1433-2965
DOI
https://doi.org/10.1007/s00198-018-4758-4

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