Safety of tibolone in the treatment of vasomotor symptoms in breast cancer patients—Design and baseline data ‘LIBERATE’ trial

Abstract

Many patients with a history of breast cancer (BC) will suffer from vasomotor symptoms, which can be induced or exacerbated by treatment with tamoxifen or aromatase inhibitors. The LIBERATE trial was designed as a randomized, double-blind, multicenter trial to demonstrate that tibolone 2.5mg/day (Livial ® ) is non-inferior to placebo regarding BC recurrence in women with vasomotor symptoms surgically treated for primary BC within the last 5 years. Secondary objectives are effects on vasomotor symptoms as well as overall survival, bone mineral density and health-related quality of life.Mean age at randomization was 52.6 years, and the mean time since surgery was 2.1 years. The mean daily number of hot flushes and sweating episodes was 7.3 and 6.1, respectively. For the primary tumor, Stage IIA or higher was reported for > 70% of the patients. In subjects whose receptor status was known, 78.2% of the tumors were estrogen receptors positive. At randomization, tamoxifen was given to 66.2% of all patients and aromatase inhibitors to 7%. Chemotherapy was reported by 5% at randomization.The adjuvant tamoxifen use in LIBERATE allows a comparison with the Stockholm trial (showing no risk of BC recurrence associated with hormone therapy), which was stopped prematurely subsequent to HABITS. The LIBERATE trial is the largest, ongoing, well-controlled study for treatment of vasomotor symptoms in BC patients.

Rationale for low-dose systemic hormone replacement therapy and review of estradiol 0.5 mg/NETA 0.1 mg

“…115,116 A previously observed increased risk for breast cancer with tibolone in an observational study 117 could have been explained due to preferential prescribing to women already at a higher risk for breast cancer. 118 However, in the LIBERATE study (Livial Intervention Following Breast Cancer: Efficacy, Recurrence And Tolerability Endpoints) -a randomised, placebo-controlled trial in women with a history of breast cancer and serious climacteric complaints, 119 terminated in May 2007 following the advice from the data safety monitoring board and the advisory board -there was a tendency for more breast cancer cases in the tibolone-treated group. 120 This illustrates that although baseline mammographic density correlates with breast cancer risk, this does not necessarily apply to the increase in mammographic density induced by HRT.…”

Climacteric Complaints after Breast Cancer – Is HRT an Option?

“…The LIBERATE (Livial Intervention following Breast cancer: Efficacy, Recurrence And Tolerability Endpoints), a prospective, randomized, double-blind, multicenter trial has been designed to investigate safety and efficacy of 2.5 mg/day oral tibolone in women with vasomotor symptoms and a history of invasive breast cancer in the previous 5 years. The primary research objective was breast cancer recurrence, secondary objectives are effects on vasomotor symptoms as well as overall survival, bone mineral density, and health-related quality of life [27]. …”