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Open Access Research article

Tibolone increases bone mineral density but also relapse in breast cancer survivors: LIBERATE trial bone substudy

Nigel J Bundred1*, Peter Kenemans2, Cheng Har Yip3, Matthias W Beckmann4, Jean-Michel Foidart5, Piero Sismondi6, Bo von Schoultz7, Rena Vassilopoulou-Sellin8, Rachid El Galta9, Eugenie Van Lieshout9, Mirjam Mol-Arts9, Juan Planellas9 and Ernst Kubista10

Author Affiliations

1 Department of Surgery, University of Manchester, Southmoor Road, Manchester, M23 9LT, UK

2 Department of Obstetrics and Gynaecology, VU University Medical Center, PO Box 7057, 1007 MB Amsterdam, The Netherlands

3 Department of Surgery, University Malaya Medical Centre, Pusat Perubatan Universiti Malaya, Lembah Pantai, 59100, Kuala Lumpur, Malaysia

4 Department of Surgery, Universitätsklinikum Erlangen, Postfach 2306, D-91012 Erlangen, Germany

5 Department of Obstetrics and Gynecology, University of Liege, 81 bd de la Constitution, B-4020 Liege, Belgium

6 Department of Gynecological Oncology, University of Turin, C.So Svizzera, 185 - 10149 Torino, Italy

7 Department of Obstetrics and Gynecology, Karolinska Institutet, SE-171 77, Stockholm, Sweden

8 Department of Pathology, The University of Texas MD Anderson Cancer Center,1515 Holcombe Blvd., Houston, TX 77030, USA

9 Research Data and Quantitative Sciences, Schering-Plough, P.O. Box 20, 5340 BH, Oss, The Netherlands

10 Department of Special Gynecology, Medical University of Vienna, Borschkegasse 8a, A-1090 Vienna, Austria

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Breast Cancer Research 2012, 14:R13  doi:10.1186/bcr3097

Published: 17 January 2012

Abstract

Introduction

The Livial Intervention Following Breast Cancer: Efficacy, Recurrence and Tolerability Endpoints (LIBERATE: Clinical http://Trials.gov webcite number NCT00408863), a randomized, placebo-controlled, double-blind trial that demonstrated that tibolone (Livial), a tissue-selective hormone-replacement therapy (HRT), increased breast cancer (BC) recurrence HR 1.40 (95% CI, 1.14 to 1.70; P = 0.001). A subgroup of women was entered into a study of bone mineral density (BMD).

Methods

Women with surgically excised primary BC (T1-3, N0-2, M-0) within the last 5 years, complaining of vasomotor symptoms, were assigned to tibolone, 2.5 mg daily, or placebo treatment for a maximum of 5 years. The BMD substudy enrolled 763 patients, using dual-energy X-ray absorptiometry (DXA) scanning at baseline and at 2 years.

Results

In the bone substudy, 699 of 763 women were eligible (345 allocated to tibolone, and 354, to placebo). After undergoing DXA scans, 300 (43%) women had normal BMD; 317 (45%), osteopenia; and 82 (11.7%), osteoporosis. Low body-mass index (P < 0.001), Asian race (P < 0.001), and late age at menarche (P < 0.04) predicted low bone mass at baseline. Tibolone increased BMD by 3.2% at the lumbar spine and 2.9% at the hip compared with placebo (both P < 0.001). The majority of fractures (55%) occurred in osteopenic patients. Women with normal BMD had increased recurrence with tibolone, 22 (15.6%) of 141 compared with placebo, 11 (6.9%) of 159 (P = 0.016), whereas no increased BC recurrence was seen in women with low BMD; 15 (7.4%) of 204 taking tibolone versus 13 (6.7%) of 195 taking placebo.

Conclusions

Tibolone is contraindicated after BC treatment, as it increases BMD and BC recurrence. Risk of BC recurrence was elevated in BC women with normal BMD (compared with low) who took tibolone.