Intraductal Therapy of Ductal Carcinoma In Situ: A Presurgery Study

Many women with ductal carcinoma in situ (DCIS) are treated with extensive surgery, radiation, and hormone therapy due to the inability to monitor the disease and to determine which cases will progress to invasive cancer. We assessed the safety and feasibility of administering chemotherapy directly into DCIS-containing ducts in 13 women before definitive surgery. The treatment was safe, feasible, and well tolerated, supporting further development of this strategy for management of DCIS. Introduction: Ductal carcinoma in situ (DCIS) is a noninvasive breast cancer wherein malignant cells are confined within a ductal lobular unit. Although less than half the cases of DCIS will progress to invasive disease, most women are treated aggressively with surgery, radiation, and/or hormone therapy due to the inability to clinically evaluate the extent and location of the disease. Intraductal therapy, in which a drug is administered directly into the mammary duct through the nipple, is a promising approach for treating DCIS, but the feasibility of instilling drug into a diseased duct has not been established. Patients and Methods: Four to 6 weeks before their scheduled surgery, 13 women diagnosed with DCIS were subjected to cannulation of the affected duct. After both the absence of perforation and presence of dye in the duct were confirmed by ductogram, pegylated liposomal doxorubicin was instilled. Histopathologic assessment was performed after surgery to assess the treatment effects. Results: Of the 13 women enrolled in the study, 6 had their DCIS duct successfully cannulated without perforation and instilled with the drug. The treatment was well tolerated, and no serious adverse events have been reported. Biomarker studies indicated a general decrease in Ki-67 levels but an increase in annexin-1 and 8-hydroxydeoxyguanosine in the lumen of DCIS-containing ducts, which suggests a local response to pegylated liposomal doxorubicin treatment. Conclusions: Intraductal therapy offers a nonsurgical strategy to treat DCIS at the site of disease, potentially minimizing the adverse effects of systemic treatment while preventing development of invasive cancer.