A Feasibility Study of the Intraductal Administration of Chemotherapy

Abstract

Preclinical data have shown the potential of the intraductal administration of chemotherapy for breast cancer prevention. Direct translation of this work has been stymied by the anatomical differences between rodents (one duct per teat) and women (5-9 ductal systems per breast). The objective of this phase I study was to show the safety and feasibility of intraductal administration of chemotherapy drugs into multiple ducts within one breast in women awaiting mastectomy for treatment of invasive cancer. Thirty subjects were enrolled in this dose escalation study conducted at a single center in Beijing, China. Under local anesthetic, one of two chemotherapy drugs, carboplatin or pegylated liposomal doxorubicin (PLD), was administered into five to eight ducts at three dose levels. Pharmacokinetic analysis has shown that carboplatin was rapidly absorbed into the bloodstream, whereas PLD, though more erratic, was absorbed after a delay. Pathologic analysis showed marked effects on breast duct epithelium in ducts treated with either drug compared with untreated ducts. The study investigators had no difficulty in identifying or cannulating ducts except in one case with a central cancer with subareolar involvement. This study shows the safety and feasibility of intraductal administration of chemotherapy into multiple ducts for the purpose of breast cancer prevention. This is an important step toward implementation of this strategy as a "chemical mastectomy", where the potential for carcinogenesis in the ductal epithelium is eliminated pharmacologically, locally, and without the need for surgery. Cancer Prev Res; 6(1); 51-58. Ó2012 AACR.

Intraductal Therapy of Ductal Carcinoma In Situ: A Presurgery Study

“…PLD is formulated to improve stability of the drug in the circulation, 28 which may also help retain the drug in the ductal system of the treated duct. 25 Of the 13 women enrolled in the study (Figure 1, for a schematic of the study design), 5 were treated with 20 mg PLD, one was treated with 4 mg PLD, one was treated with saline solution, 3 had duct perforations, and 3 had ducts that were either not found or not able to be cannulated (Table 1). We referred to the patients’ mammograms to identify the affected duct (Figure 2A, B) and also used ductography during the procedure to confirm that we had cannulated the correct duct and that it was intact (Figure 2C).…”

“…25 For each case, immunohistochemical analysis was performed on 2 representative paraffin-embedded tissue blocks, one from a region that contained DCIS and one from a noncancerous area. For the staining, 4- μ m-thick tissue sections were prepared.…”

“…Conversely, drug concentrations in the breast were considerably higher in women who received intraductal PLD compared with those administered intravenous PLD. In a separate study, Love et al 25 instilled 1 of 2 drugs, carboplatin or PLD, into 5 to 8 ducts per breast in 30 women 2 to 3 days before mastectomy. There were no adverse events, and both drugs were found to cause dose-dependent effects on ductal histology.…”

Autologous Fat Grafting as a Novel Antiestrogen Vehicle for the Treatment of Breast Cancer

“…For breast cancer, approaches have included implantable hydrogels, wafers, rods, and films that act as depots (12), which are often designed to biodegrade and thus eliminate the need for surgical removal, topical applications that facilitate transdermal delivery (19, 20), intraductal administration (21, 22), and iontophoretic devices that utilize electric fields to drive and direct drug diffusion (23, 24). An adipose depot has several advantages over these other approaches.…”

Combining the strength of genomics, nanoparticle technology, and direct intraductal delivery for breast cancer treatment

“…We used i.duc injection of slow-release liposomal doxorubicin (Doxil) to successfully eliminate preneoplasias in both the HER/2 neu transgenic mouse and carcinogen-induced rat mammary tumor models [5] and to delay carcinoma formation by using curcumin [6]. We [7] and others [8] also demonstrated the feasibility and safety of the i.duc approach by using Doxil in women undergoing mastectomy for breast cancer. However, the use of DNA-synthesis-targeted drugs carries the risk of iatrogenic cancer in the distant future.…”