Ductal access for prevention and therapy of mammary tumors

Satoshi Murata, Scott L. Kominsky, Mustafa Vali, Zhe Zhang, Elizabeth Garrett-Mayer, Dorian Korz, David Huso, Sharyn D. Baker, James Barber, Elizabeth Jaffee, R. Todd Reilly, Saraswati Sukumar

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)638-645
Number of pages8
JournalCancer Research
Volume66
Issue number2
DOIs
StatePublished - Jan 15 2006

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Murata, S., Kominsky, S. L., Vali, M., Zhang, Z., Garrett-Mayer, E., Korz, D., Huso, D., Baker, S. D., Barber, J., Jaffee, E., Reilly, R. T., & Sukumar, S. (2006). Ductal access for prevention and therapy of mammary tumors. Cancer Research, 66(2), 638-645. https://doi.org/10.1158/0008-5472.CAN-05-4329