The Effects of Tamoxifen on Plasma Lipoprotein(a) Concentrations: Systematic Review and Meta-Analysis

Introduction: Tamoxifen is a selective estrogen receptor modulator widely used in the treatment of breast cancer. Tamoxifen therapy is associated with reduced circulating low-density lipoprotein cholesterol and increased triglycerides, but its effects on other lipids are less-well studied. Aims: We aimed to investigate the effect of tamoxifen on circulating concentrations of lipoprotein(a) (Lp(a)) through systematic review and meta-analysis of available randomized controlled trials (RCTs) and observational studies. Methods: This study was registered in the PROSPERO database (CRD42016036890). Scopus, Medline and EMBASE were searched from inception until 22nd March 2016 to identify studies investigating the effect of tamoxifen on Lp(a) values in humans. Results: Meta-analysis of 5 studies with 284 participants suggested a significant reduction of Lp(a) levels following tamoxifen treatment (weighted mean difference [WMD]: -3.53 mg/dL, 95% confidence interval [CI]: -6.53, -0.53, p=0.021). When studies were categorized according tamoxifen dose, there was a significant effect in the subset of studies with administered doses ≥20 mg/day (WMD: -5.05 mg/dL, 95% CI: -7.86, -2.23, p<0.001), but not in the subset with doses <20 mg/day (WMD: -1.41 mg/dL, 95% CI: -5.13, 2.31, p=0.458). With respect to duration of treatment, a greater effect was observed in subgroup of studies administering tamoxifen for <12 weeks (WMD: -4.01 mg/dL, 95% CI: -7.84, -0.18, p=0.04) versus the subgroup of studies lasting ≥12 weeks (WMD: -2.48 mg/dL, 95% CI: -5.50, 0.53, p=0.107). Conclusions: Meta-analysis suggested a significant reduction of Lp(a) levels following tamoxifen treatment. Further well-designed trials are required to validate these results