Abstract OT2-01-04: Freezing instead of resection of small breast tumors (FROST): A study of cryoablation in the management of early stage breast cancer
Authors: Coronado GM , Ho ET , Holmes DR 
Published: February 2018

Abstract
Background/Objective: ACOSOG Z1072 demonstrated complete target tumor ablation in 92% of stage I invasive breast cancers treated with cryoablation prior to resection. We hypothesize that cryoablation can achieve complete tumor ablation and adequate local control in a selected population of women with early stage invasive breast cancer managed with cryoablation alone, without planned surgical resection.
Methods: The trial is a phase II, single-arm, multicenter study open to women age 50 and older with core needle biopsy-proven clinical stage I, T1, clinically node negative (N0), unifocal, hormone receptor positive, HER2/neu-negative invasive ductal carcinoma measuring ≤1.5 cm by mammography (MG), ultrasound (US), and MRI. Once registered, subjects will undergo US-guided cryoablation followed 6 months later by an US-guided core biopsy of the cryoablated lesion to confirm the absence of residual viable disease. Following cryoablation, subjects will also begin a minimum 5-year course of adjuvant endocrine therapy and serial MG, US, and MRI. Whole breast radiotherapy (WBRT) is optional for subjects age 70+ (stratum I) and mandatory for women age 50-69 (stratum 2). Sentinel node biopsy (SNBx) is optional in both cohorts. All subjects found to have residual or recurrent disease will undergo standard surgical resection.
Study SchemaRegistrationCryoablation6 MonthsSemiannualAnnualResectionAge 50+, tumor size ≤ 1.5 cm, unifocal, N0, biopsy proven invasive breast cancerFollowed by endocrine therapy (all patients); WBRT (Stratum 2); SNBx (optional)MG, US, MRI, needle biopsy; resection of residual cancer or serial follow up if absentUnilateral US or MG X 3 yearsBilateral MG and MRIRecurrent/residual breast or axillary cancer
The trial was activated in June 2016. The study is currently open at 6 sites with up to 30 sites planned. A total of 110 eligible subjects will be enrolled in each stratum for total accrual goal of 220. Enrollment is planned over 3 years followed by 5 years of follow-up.
Results: The primary endpoint of the study will be to determine the rate of complete tumor ablation in patients treated with cryoablation, defined as absence of residual viable carcinoma detected by core needle biopsy of the ablation site performed 6-months post-cryoablation. The secondary endpoint will be to determine the 5-year ipsilateral breast tumor recurrence rate in patients treated with cryoablation without subsequent resection. Local recurrence will be defined as recurrence of cancer within the index quadrant confirmed histologically by needle biopsy. Breast cosmesis (assessed by BCCT.core) and adverse events will also be evaluated.
Conclusions: If the FROST Trial is successful at achieving complete ablation in ≥ 80% of study subjects, the trial will provide an important foundation for establishing cryoablation as an alternative to conventional therapy in selected women with early stage invasive breast cancer.
If interested, please contact Pam Ellis, clinical coordinator, at (925)460-6080 or pellis@sanarus.com.
Citation Format: Coronado GM, Ho ET, Holmes DR. Freezing instead of resection of small breast tumors (FROST): A study of cryoablation in the management of early stage breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr OT2-01-04.