title: Tibolone increases bone mineral density but also relapse in breast cancer survivors: LIBERATE trial bone substudy.
abstract: BACKGROUND
  The Livial Intervention Following Breast Cancer: Efficacy, Recurrence and Tolerability Endpoints (LIBERATE: Clinical http://Trials.gov 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.
authors.affiliation: Department of Surgery, University of Manchester, Southmoor Road, Manchester, M23 9LT, UK. bundredn@manchester.ac.uk
authors.forename: Nigel J
authors.initials: NJ
authors.lastname: Bundred
authors.forename: Peter
authors.initials: P
authors.lastname: Kenemans
authors.forename: Cheng Har
authors.initials: CH
authors.lastname: Yip
authors.forename: Matthias W
authors.initials: MW
authors.lastname: Beckmann
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Foidart
authors.forename: Piero
authors.initials: P
authors.lastname: Sismondi
authors.forename: Bo von
authors.initials: Bv
authors.lastname: Schoultz
authors.forename: Rena
authors.initials: R
authors.lastname: Vassilopoulou-Sellin
authors.forename: Rachid El
authors.initials: RE
authors.lastname: Galta
authors.forename: Eugenie Van
authors.initials: EV
authors.lastname: Lieshout
authors.forename: Mirjam
authors.initials: M
authors.lastname: Mol-Arts
authors.forename: Juan
authors.initials: J
authors.lastname: Planellas
authors.forename: Ernst
authors.initials: E
authors.lastname: Kubista
mesh_terms: D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D015992:Body Mass Index; D015519:Bone Density / Q000187:drug effects*; D050071:Bone Density Conservation Agents / Q000009:adverse effects*; D001943:Breast Neoplasms / Q000139:chemically induced* / Q000601:surgery; D004311:Double-Blind Method; D015914:Estrogen Replacement Therapy; D005260:Female; D006801:Humans; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000139:chemically induced*; D009652:Norpregnenes / Q000009:adverse effects*; D010024:Osteoporosis / Q000517:prevention & control*; D020845:Selective Estrogen Receptor Modulators / Q000009:adverse effects*; D017741:Survivors
chemical_list: D050071:Bone Density Conservation Agents; D009652:Norpregnenes; D020845:Selective Estrogen Receptor Modulators; C027385:tibolone