Based on observations in preclinical studies that PLD decreased tumor volume, eradicated premalignant disease, and prevented the development of new epithelial lesions, the breast group at Johns Hopkins conducted a phase I trial assessing the feasibility and safety of intraductally administered PLD in women with breast cancer.20 In this clinical study, women 18 years and older with a diagnosis of in situ or invasive breast cancer were enrolled. Patients with inflammatory breast cancer or prior surgical procedures that might have altered the ductal anatomy were excluded. The investigators sought to determine the maximum-tolerated dose of PLD administered to a single human lactiferous duct, in vivo, before mastectomy. The pharmacokinetics of intraductally administered PLD were evaluated, including the determination of serial concentrations of doxorubicin and doxorubicinol, a metabolite of doxorubicin, in plasma and tissue. The dose of PLD was escalated from 2 mg to a maximum dose of 10 mg, which was administered on day 0 of the trial, with samples taken for pharmacokinetic studies on days 1, 2, 8, and the day of surgery. All patients were monitored for adverse drug reactions.