Effect of tibolone on tumor angiogenesis parameters in short-term treated women

Abstract

10519 Background: Large recent studies have shown increased mammographic density, breast pain and a marginally increased risk of breast cancer in women treated with continuous combined estrogen/progestogen (ccEPT), while tibolone has a minimal effect. A placebo-controled clinical trial (STEM), approved by several ethical comities, has been initiated to assess effect and potential mechanism of action of tibolone on breast tumor. We present the results on 12 angiogenesis-related parameters. Methods: 102 women with breast cancer who had to undergo a mastectomy were treated for 2 weeks with tibolone 2.5 mg/day or placebo. RNA was extracted from tumor snap-frozen biopsies (paired before and after treatments) and reverse-transcripted into 2 cDNA batches on which 6 distinct PCRs were performed in duplicate per parameter/sample. A vascular density (VD) index was determined on CD31 specifically stained tumor sections by counting 10 fields per section on 5 distinct sections per biopsy. Results: The validity of the VD evaluation is highlighted by the high correlation coefficient (r = 0.81) between the data within the placebo group at a 2 week interval. In the tumor samples, no change of the VD index was seen. Since it could be argued that VD index could not correctly reflect a modulation of angiogenesis after only 14 days of treatment, we looked at a potential change of the expression of a large array of angiogenesis-related factors (VEGFs, VEGFRs, PAI-1). No modification of the expression in any of these factors was observed. Conclusions: Our data lead to conclude that, in this study, tibolone displays a neutral effect on angiogenesis in breast tumor. [Table: see text]