Local delivery of hormonal therapy with silastic tubing for prevention and treatment of breast cancer

Sci Rep. 2018 Jan 8;8(1):92. doi: 10.1038/s41598-017-18436-1.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antineoplastic Agents, Hormonal / administration & dosage*
  • Antineoplastic Agents, Hormonal / pharmacokinetics
  • Biomarkers, Tumor
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology*
  • Breast Neoplasms / prevention & control*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Chemoprevention* / methods
  • Chromatography, Liquid
  • Disease Models, Animal
  • Estradiol / administration & dosage
  • Estradiol / analogs & derivatives
  • Estradiol / pharmacokinetics
  • Estrogen Receptor Modulators / administration & dosage
  • Estrogen Receptor Modulators / pharmacokinetics
  • Female
  • Fulvestrant
  • Germ-Line Mutation
  • Humans
  • Tandem Mass Spectrometry
  • Tissue Distribution
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents, Hormonal
  • Biomarkers, Tumor
  • Estrogen Receptor Modulators
  • Fulvestrant
  • Estradiol