Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Atossa Therapeutics, Inc., Seattle, WA, USA.
Oncologist. 2022 Jul 5;27(7):e597-e600. doi: 10.1093/oncolo/oyac102.
Although breast cancer incidence is increasing, there are few primary preventive initiatives. Tamoxifen can reduce breast cancer incidence but is rarely used for primary prevention due to adverse events and tolerance issues. We tested if endoxifen, a tamoxifen metabolite, applied directly to the skin of the breast, could reduce mammographic density, a proxy for therapy response. Ninety women were randomized to placebo, 10 and 20 mg of topical Z-endoxifen for 6 months. Mammographic density and symptoms were measured at baseline and study exit. Despite a high discontinuation rate, driven by skin rashes, we found a significant mammographic density decrease, a dose-dependent increase in the concentration of plasma Z-endoxifen but no systemic side effects. Topical application of tamoxifen metabolites has the potential to decrease breast cancer incidence without major systemic side effects. However, endoxifen may not be suitable for topical administration and is unlikely to be used for breast cancer prevention.
尽管乳腺癌的发病率在上升，但初级预防措施却很少。他莫昔芬可以降低乳腺癌的发病率，但由于不良反应和耐受性问题，很少用于初级预防。我们测试了一种他莫昔芬的代谢物——依西美坦，直接应用于乳房皮肤，是否可以降低乳房 X 光密度，这是治疗反应的一个替代指标。90 名女性被随机分配到安慰剂组、10mg 和 20mg 外用 Z-依西美坦组，疗程为 6 个月。在基线和研究结束时测量乳房 X 光密度和症状。尽管由于皮疹导致停药率很高，但我们发现乳房 X 光密度显著下降，血浆 Z-依西美坦浓度呈剂量依赖性增加，但没有全身副作用。他莫昔芬代谢物的局部应用有可能降低乳腺癌的发病率，而不会产生重大的全身副作用。然而，依西美坦可能不适合局部给药，不太可能用于乳腺癌预防。
