ABSTRACT
OBJECTIVE: To determine the feasibility and efficacy of cryosurgery of breast cancer. DESIGN: In phase 1, carcinogen-induced mammary adenocarcinomas in 13 Sprague-Dawley rats were treated by cryosurgery and were then examined for histopathologic change. In phase 2, transplantable mammary adenocarcinomas in 50 DBA/IJ mice were treated by cryosurgery to determine the effect of varying tumor temperatures, and duration and number of freeze-thaw cycles on tumor viability. In phase 3, 2- to 3-cm ultrasound-monitored cryolesions were formed in the breasts of 4 dogs and 4 sheep. These animals were followed up for procedure-related complications; the histopathologic necrosis of the cryolesions were correlated with the ultrasound images. Based on the results of these experiments, ultrasound-guided cryosurgery of breast cancer was initiated in a human clinical trial. RESULTS: In phase 1, a single, short-term (< 7 minutes) freeze killed only tumors smaller than 1.5 cm in diameter, despite an apparent decrease to -40 degrees C at the periphery of each tumor. In phase 2, varying the peripheral tumor temperature to as low as -70 degrees C, using a single, short-term (< 7 minutes) freeze did not alter the results from phase 1. If the ice ball fully encompassed the tumor, however, maintaining it for at least 15 minutes achieved 100% tumor kill independent of tumor size. In phase 3, creation of a reproducible ultrasound-monitored cryolesion was facilitated when 2 freeze-thaw cycles were performed. No procedure-related complications were noted. In the human trial, 2 invasive lobular carcinomas from 1 patient were treated by cryosurgery and were negative for persistent tumor by core needle biopsy performed 4 and 12 weeks after a well-tolerated procedure. CONCLUSIONS: In situ breast cryosurgery has been proved to be feasible and efficacious in small and large animal studies and has been successfully performed in 1 patient with breast cancer. The results of this study suggest that ultrasound-guided cryosurgery of breast cancer warrants further investigation.
