title: Cryosurgery of breast cancer.
abstract: OBJECTIVE
  To determine the feasibility and efficacy of cryosurgery of breast cancer.
  
  
  METHODS
  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.
authors.affiliation: Department of General Surgery, Rush-Presbyterian-St Luke's Medical Center, Chicago, Ill., USA.
authors.forename: E D
authors.initials: ED
authors.lastname: Staren
authors.forename: M S
authors.initials: MS
authors.lastname: Sabel
authors.forename: L M
authors.initials: LM
authors.lastname: Gianakakis
authors.forename: G A
authors.initials: GA
authors.lastname: Wiener
authors.forename: V M
authors.initials: VM
authors.lastname: Hart
authors.forename: M
authors.initials: M
authors.lastname: Gorski
authors.forename: K
authors.initials: K
authors.lastname: Dowlatshahi
authors.forename: B F
authors.initials: BF
authors.lastname: Corning
authors.forename: M F
authors.initials: MF
authors.lastname: Haklin
authors.forename: G
authors.initials: G
authors.lastname: Koukoulis
mesh_terms: D000230:Adenocarcinoma / Q000000981:diagnostic imaging / Q000601:surgery*; D000368:Aged; D000818:Animals; D001943:Breast Neoplasms / Q000000981:diagnostic imaging / Q000601:surgery*; D003452:Cryosurgery / Q000379:methods; D004285:Dogs; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D015674:Mammary Neoplasms, Animal / Q000000981:diagnostic imaging / Q000601:surgery*; D051379:Mice; D008811:Mice, Inbred DBA; D051381:Rats; D017207:Rats, Sprague-Dawley; D012756:Sheep; D014463:Ultrasonography