Beneficial effects of transdermal administration of tamoxifen on capsular contracture after breast implantation in murine models

Background and aim Capsular contracture is the most common complication with smooth-type silicone implants. We investigated the preventive effect of an active metabolite of tamoxifen, 4-hydroxytamoxifen (4-OH TAM), on capsular contracture. Methods A silicone sheet was implanted into the back of 28 female ICR mice. Mixtures of gel with 0.2% 4-OH TAM and 0.1% 4-OH TAM were administered transdermally once a day for 4 weeks. Saline was administered to the control. After killing the mice, capsular thickness was measured in H&E-stained specimens. Estrogen receptor (ER), alpha-smooth muscle actin (alpha-SMA), and transforming growth factor-beta (TGF-beta) expressions were immunohistochemically investigated in the capsules. Results The capsule was thinner in the 0.2% 4-OH TAM gel group than in the control group (control, 0.1% 4-OH TAM gel, 0.2% 4-OH TAM gel: 52.8 +/- 3.4 mu m, 54.2 +/- 6.8 mu m, 46.4 +/- 3.3 mu m, respectively). ER was found in most fibroblasts of all samples. alpha-SMA expression in the capsule was significantly lower in the 4-OH TAM gel groups than in the control group (control = 70.0 +/- 3.4%, 0.1% 4-OH TAM = 57.0 +/- 3.4%, 0.2% 4-OH TAM = 49.4 +/- 4.9%). TGF-beta expression was significantly reduced by the 4-OH TAM gel injections dose-dependently (control = 67.3 +/- 2.2%, 0.1% 4-OH TAM = 52.4 +/- 3.1%, 0.2% 4-OH TAM = 45.1 +/- 2.4%). Conclusions The transdermal administration of 0.1% and 0.2% 4-OH TAM gels inhibited capsule development. The inhibition of TGF-beta expression is a mechanism by which 4-OH TAM suppresses fibroblast growth, preventing capsular formation.