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.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Murata S,Kominsky SL,Vali M,Zhang Z,Garrett-Mayer E,Korz D,Huso D,Baker SD,Barber J,Jaffee E,Reilly RT,Sukumar Sdoi
10.1158/0008-5472.CAN-05-4329subject
Has Abstractpub_date
2006-01-15 00:00:00pages
638-45issue
2eissn
0008-5472issn
1538-7445pii
66/2/638journal_volume
66pub_type
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