Division of Hematology and Oncology, University of California, San Francisco, USA.
Department of Molecular and Cell Biology, University of California, Berkeley, USA.
Sci Rep. 2018 Jan 8;8(1):92. doi: 10.1038/s41598-017-18436-1.
Broad use of germline testing has identified an increasing number of women at risk for breast cancer with a need for effective chemoprevention. We report a novel method to selectively deliver various anti-estrogens at high drug levels to the breast tissue by implanting a device comprised of silastic tubing. Optimized tubing properties allow elution of otherwise poorly bioavailable anti-estrogens, such as fulvestrant, into mammary tissue in vitro and in vivo with levels sufficient to inhibit estrogen receptor activation and tumor cell proliferation. Implantable silastic tubing delivers fulvestrant selectively to mouse mammary fat tissue for one year with anti-tumor effects similar to those achieved with systemic fulvestrant exposure. Furthermore, local delivery of fulvestrant significantly decreases cell proliferation, as assessed by Ki67 expression, most effectively in tumor sections adjacent to tubing. This approach may thereby introduce a potential paradigm shift and offer a promising alternative to systemic therapy for prevention and early interception of breast cancer.
广泛使用种系检测已经确定了越来越多有乳腺癌风险的女性，她们需要有效的化学预防。我们报告了一种新方法，通过植入由硅橡胶管组成的装置，将各种抗雌激素选择性递送到乳腺组织中，以实现高药物水平。优化的管腔特性允许将其他生物利用度差的抗雌激素（如氟维司群）洗脱到体外和体内的乳腺组织中，其水平足以抑制雌激素受体激活和肿瘤细胞增殖。可植入的硅橡胶管可将氟维司群选择性地递送到小鼠乳腺脂肪组织中长达一年，其抗肿瘤效果与全身氟维司群暴露相似。此外，通过 Ki67 表达评估，氟维司群的局部递送最有效地降低了细胞增殖，尤其是在与管腔相邻的肿瘤切片中。这种方法可能会引入一种潜在的范式转变，并为预防和早期干预乳腺癌的全身治疗提供一种有前途的替代方案。
