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Osteoporosis International

, Volume 30, Issue 1, pp 187–200 | Cite as

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

  • R. Hamood
  • H. HamoodEmail author
  • I. Merhasin
  • L. Keinan-Boker
Original Article

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.

Keywords

Aromatase inhibitor Bone health Breast cancer Osteoporosis Survivorship Tamoxifen 

Abbreviations

AI

Aromatase inhibitor

ARF

Attributable risk fraction

ATC

Anatomic therapeutic chemical

BC/S

Breast cancer/survivors

BMD

Bone mineral density

CI

Confidence interval

CIF

Cumulative incidence function

HR

Hazard ratio

HT

Hormone therapy

ICD-9

International classification of diseases, ninth revision

IDR

Incidence density rate

IDRR

Incidence density rate ratio

INCR

Israel National Cancer Registry

IQR

Interquartile range

LHS

Leumit Health Services

P

P value

PAF

Population attributable fraction

SE

Standard error

SIDR

Standardized incidence density rate ratio

χ2

Chi square

Notes

Acknowledgements

We gratefully acknowledge all participating breast cancer survivors, Dr. Natan Kahan, and the Ph.D. advisory committee for their invaluable contribution.

Funding

Funding of this study was in part provided by a grant from the Council for Higher Education (grant no. 11658745) in collaboration with the Graduate Studies Authority at the University of Haifa (grant no. 11658760). The sponsors have no role in the collection, analysis, and interpretation of data.

Compliance with ethical standards

Ethics approval

The study protocol was duly approved by the Institutional Review Boards of LHS and the University of Haifa.

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Conflicts of interest

None.

Disclaimer

The results, conclusions, view and opinions contained herein are those of the authors and not to be construed as the official policy of Israel’s Ministry of Health, or of Leumit Health Organization.

Supplementary material

198_2018_4758_MOESM1_ESM.ppt (142 kb)
ESM 1 Flow chart of participants in the study. (PPT 141 kb)
198_2018_4758_MOESM2_ESM.pdf (44 kb)
ESM 2 (PDF 43 kb)

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Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2018

Authors and Affiliations

  1. 1.School of Public HealthUniversity of HaifaHaifaIsrael
  2. 2.Leumit Health ServicesKarmielIsrael
  3. 3.Leumit Health ServicesNetanyaIsrael
  4. 4.Ministry of HealthIsrael Center for Disease ControlRamat GanIsrael

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