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-NV -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. (Cancer Res 2006; 66(2): 638-45)

Initiation of Metastatic Breast Carcinoma by Targeting of the Ductal Epithelium with Adenovirus-Cre: A Novel Transgenic Mouse Model of Breast Cancer

“…We recommend practicing this step by injecting trypan blue or some other sterile traceable dye inside of the duct and preparing whole mammary mounts to confirm targeting of the ductal tree. Additionally, other protocols describing intraductal injection of reagents have been published 33,34 , which may be useful for developing proper technique. Issues with viral preparation or infection of the ductal lumen can also be investigated by using a mCherry expressing adenovirus.…”

Hypermethylated Genes as Biomarkers of Cancer in Women with Pathologic Nipple Discharge

“…The development of a nonsurgical method to reliably diagnose cancer would offer the possibility of diagnosis without surgery in women with PND who have a very low likelihood of significant neoplasia. In the future, a molecular diagnostic test that allows reliable diagnosis of intraductal pathology will enable in situ ablation of benign lesions with either endoscopic techniques or the intraductal administration of antineoplastic agents (19).…”

A Feasibility Study of the Intraductal Administration of Chemotherapy

“…For example, Okugawa and colleagues showed that rats with N-methyl N'-nitrosourea (MNU)-induced breast tumors exhibited significant reduction in tumor burden and total number of mammary carcinomas when treated with intraductal paclitaxel (27). Similarly, Sukumar and colleagues have shown that intraductal administration of various anticancer drugs, such as pegylated liposomal doxorubicin (PLD), 4-hydroxytamoxifen carboplatin, methotrexate, nanoparticle albuminbound paclitaxel, and 5-fluorouracil was associated with a significant reduction in tumor formation or protected against tumor development in the MNU model, and also minimized the toxic effects of the drugs (28,29). The same group has also shown that in the HER2/neu transgenic mouse (neu-N) model, which spontaneously develops neu-overexpressing multifocal mammary adenocarcinoma beginning at approximately 4 to 5 months of age, intraductal PLD treatment resulted in significantly reduced risk of developing breast tumors.…”