A long-term fulvestrant eluting implant is safe, non-toxic, and reduces the risk of breast cancer in in vivo models.

For individuals at high risk of developing breast cancer, interventions to mitigate this risk include surgical removal of their breasts and ovaries or five years treatment with the anti-estrogen tamoxifen or aromatase inhibitors. We hypothesized that a silicone based anti-estrogen-eluting implant placed within the breast would provide the risk reduction benefit of hormonal therapy, but without the adverse effects that limit compliance. To this end, we demonstrate that when placed adjacent to mammary tissue in the DMBA-induced rat breast cancer model a fulvestrant-eluting implant delays breast cancer with minimal systemic exposure. Using adult female sheep, fulvestrant-eluting implants were found to be safe and non-toxic when placed at the base of the udder for directed elution into the mammary tissue. At 30 days of elution, fulvestrant was found to penetrate mammary tissue forming a concentration gradient beyond 15 mm from the implant. Consistent with the small animal rat study, minimal systemic fulvestrant biodistribution was found. Together, these studies provide the proof of principle that a breast indwelling fulvestrant-eluting implant can reduce the risk of breast cancer and limit systemic exposure, while penetrating and distributing through breast tissue.
Competing Interests: Declarations COMPETING INTERESTS PNM, ST, PD, and NP are listed as inventors on UCSF patents pertaining to drug eluting implants for the treatment and prevention of cancer. PNM and ST are founders of Alessa Therapeutics, own stock, and remain paid consultants. Alessa Therapeutics develops drug eluting implants for the treatment of prostate cancer. PD contributed to this work while an employee of UCSF, and is now an employee of both UCSF and Alessa Therapeutics. All other authors have no competing interests.