Ductal access for prevention and therapy of mammary tumors.
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.
Murata
Satoshi
S
Department of Oncology, Johns Hopkins University School of Medicine, 1650 Orleans Street, Baltimore, MD 21231, USA.
Kominsky
Scott L
SL
Vali
Mustafa
M
Zhang
Zhe
Z
Garrett-Mayer
Elizabeth
E
Korz
Dorian
D
Huso
David
D
Baker
Sharyn D
SD
Barber
James
J
Jaffee
Elizabeth
E
Reilly
R Todd
RT
Sukumar
Saraswati
S
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
D004965:Estrogen Antagonists; C506643:liposomal doxorubicin; D013629:Tamoxifen; C016601:afimoxifene; D011092:Polyethylene Glycols; D004317:Doxorubicin