title: Ductal access for prevention and therapy of mammary tumors.
abstract: In cancer patients and in those at high risk, systemic exposure to agents for therapy or prevention is accompanied by undesirable side effects. We hypothesized that it is possible to prevent and treat breast cancer by introducing anticancer agents into the mammary ductal network. Here, we show the efficacy of intraductally administered anticancer agents 4-hydroxytamoxifen and pegylated liposomal doxorubicin (PLD) in the prevention and treatment of breast cancer using the rat N-methyl-N'-nitrosourea-induced and spontaneous HER-2/neu transgenic mouse (neu-N) models of breast cancer. Intraductal administration of PLD to neu-N mice caused regression of established tumors and prevented tumor development more effectively than i.v. injection (P < 0.0001). Intraductal administration resulted in lower circulating levels of PLD compared with i.v. administration, with no evidence of systemic toxicity or long-term histopathologic changes in the mammary gland. Compared with systemic administration, intraductal injection provides direct access to breast lesions with higher local and lower systemic drug exposure. These studies suggest that this approach has potential for application to prevention and neoadjuvant therapy of early breast cancer.
authors.affiliation: Department of Oncology, Johns Hopkins University School of Medicine, 1650 Orleans Street, Baltimore, MD 21231, USA.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Murata
authors.forename: Scott L
authors.initials: SL
authors.lastname: Kominsky
authors.forename: Mustafa
authors.initials: M
authors.lastname: Vali
authors.forename: Zhe
authors.initials: Z
authors.lastname: Zhang
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Garrett-Mayer
authors.forename: Dorian
authors.initials: D
authors.lastname: Korz
authors.forename: David
authors.initials: D
authors.lastname: Huso
authors.forename: Sharyn D
authors.initials: SD
authors.lastname: Baker
authors.forename: James
authors.initials: J
authors.lastname: Barber
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Jaffee
authors.forename: R Todd
authors.initials: RT
authors.lastname: Reilly
authors.forename: Saraswati
authors.initials: S
authors.lastname: Sukumar
mesh_terms: D000818:Animals; D004317:Doxorubicin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D004333:Drug Administration Routes; D004965:Estrogen Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008321:Mammary Glands, Animal; D015674:Mammary Neoplasms, Animal / Q000517:prevention & control*; D051379:Mice; D008822:Mice, Transgenic; D020360:Neoadjuvant Therapy; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D013629:Tamoxifen / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D004965:Estrogen Antagonists; C506643:liposomal doxorubicin; D013629:Tamoxifen; C016601:afimoxifene; D011092:Polyethylene Glycols; D004317:Doxorubicin