Is tibolone (Livial, Xyvion) associated with an increased risk of breast cancer?

Comments from: Professor Henry Burger AO, MD, FRACP, FCP, FRCP (London), FRCOG, FRANZCOG, FAA
Director and Consultant Endocrinologist, The Jean Hailes Foundation for Women's Health, and Emeritus Director, Prince Henry's Institute of Medical Research.

Tibolone (sold as Livial or Xyvion) is probably not associated with an increased risk of breast cancer. The most recent data are from the LIFT trial¹, showing a decreased risk (HR 0.32) in a randomised controlled trial (RCT) where the dose was half of that conventionally used, 1.25 mg daily. This was a three year trial in women over 60 years of age and well past menopause, and may not reflect the situation of women treated closer to the menopause.  There is a large case-control study from the UK general practice research database², which found no increase in risk (HR 0.86). The data suggesting an increased risk in the Million Women Study³ is almost certainly due to selection bias.

The other data, published by Kenemans et al in Lancet Oncology 10:135-146, 2009, with a subsequent correction (10:209), is from the LIBERATE trial - a RCT of tibolone versus placebo in women who were symptomatic after breast cancer treatment. After three years, there was a significant increase in risk of recurrence in those treated with tibolone. In the placebo arm the risk was 10.7 per cent and in the tibolone arm, 15.2 per cent. It was concluded that a history of breast cancer should remain as a contraindication for the use of tibolone. It could be hypothesised that the tibolone may have impaired the risk reducing effects of the adjuvant therapy which many of the women were receiving.

References

1. Cummings SR, Ettinger B, Delmas PD, et al. for the LIFT Trial investigators. ‘The effects of tibolone in older postmenopausal women’. N Engl J Med 2008;359:697-708 

2.  Opatrny L, Dell'Aniello S, Assouline S, Suissa S. Hormone replacement therapy use and variations in the risk of breast cancer. BJOG. 2008 Jan;115(2):169-75

3. ‘Breast Cancer and hormone-replacement therapy in the Million Women Study’. Lancet 2003; 362419-427

4. Kenemans P, Bundred NJ et al. ‘Safety and efficacy of tibolone in in breast cancer patients with vasomotor symptoms: A double –blind, randomised, non-inferiority trial’. Lancet Oncol 10: 135-146, 2009.

Content Updated July 19, 2011