Livial Intervention Following Breast Cancer; Efficacy, Recurrence and Tolerability Endpoints (LIBERATE)(COMPLETED)(P05885)

Inclusion Criteria:

• Histologically confirmed and surgically treated invasive breast carcinoma (T1/2/3 N0/1/2 M0), irrespective of hormonal (estrogen/progestogen) receptor status.
• Last menstrual bleeding at least 12 months before the start of the study or ovariectomized or hysterectomized or currently being treated with gonadotropin releasing hormone analogs.
• Vasomotor symptoms whether related to natural menopause, ovariectomy, or to breast cancer therapy (chemotherapy, tamoxifen, aromatase inhibitors or other anticancer therapy).

• In subjects with an intact uterus, a 'normal' endometrium, defined as:

  1. in tamoxifen users: absence of endometrial polyps
  2. in non-tamoxifen users: double layer endometrial thickness <=4 mm as assessed by TVUS or double layer endometrial thickness >4 mm and <=8 mm as assessed by TVUS plus an endometrial biopsy result of inactive/atrophic.
• Voluntary written informed consent and willing and able to make reasonable efforts to meet all clinical trial requirements.

Exclusion Criteria:

• Age >75 years at baseline.
• Ductal carcinoma in situ (DCIS) of the breast without the existence of invasive breast carcinoma.
• Invasive breast carcinoma having a tumor of any size with direct extension to chest wall or skin (T4) and/or having metastasis to ipsilateral mammary lymph node(s) (N3) and/or having presence of distant metastasis (M1).
• Surgical treatment of the primary breast cancer >5 years ago.
• History or presence of residual or recurrent breast cancer.
• History or presence of endometrial cancer.
• History or presence of any other malignancy (besides breast cancer and endometrial cancer) within the past 5 years, except for adequately treated basal cell carcinoma of the skin.
• Diagnostic findings suspicious for any malignancy.
• Double layer endometrial thickness >8 mm as assessed by TVUS in subjects not being treated with tamoxifen.
• Final diagnosis of endometrial biopsy different from inactive/atrophic
• Existence of endometrial polyps as demonstrated by TVUS.
• Undiagnosed vaginal bleeding.
• Abnormal cervical smear (corresponding to PAP IIb or higher)
• Any previous or current unopposed estrogen administration in women with an intact uterus (occasional use of estrogen-containing vaginal cream was allowed after an appropriate washout period - see below).
• Use of systemic estrogens and/or progestogens (including intra-uterine progestogen therapy) and/or tibolone and/or phytoestrogens within 8 weeks prior to baseline; use of transdermal hormone therapy and/or local estrogen applications and/or non-hormonal medication for vasomotor symptoms within 4 weeks prior to baseline.
• Use of progestogen implants or injections and/or estrogen/progestogen injectable therapy within the past 6 months.
• Use of estrogen implants or injections within the past 5 years.
• Use of raloxifene hydrochloride and/or any non-registered investigational drug within the last 8 weeks.
• Active deep vein thrombosis, thromboembolic disorders, or a documented history of these conditions.
• Severe liver disorders.
• Abnormal laboratory values considered to be clinically relevant by the investigator.
• Any disease or condition that is clinically relevant and which, in the opinion of the investigator, would jeopardize the subject's well-being during the course of the trial.
• Known hypersensitivity to tibolone or any of its components
• Known or suspected pregnancy
• Age <40 years at baseline and planned breast cancer therapy <2 years after baseline