Cryoablation is an emerging minimally invasive ablative technique for selected patients with early-stage breast cancer. The FIRST (FreezIng bReaST cancer in Brazil) trial was designed to evaluate the pathological efficacy and safety of cryoablation followed by surgery, to assess the accuracy of imaging modalities in predicting complete pathological response, and to explore technical predictors of successful tumor ablation.

This prospective, multicenter, non-randomized, single-arm phase II study enrolled adults with unifocal invasive breast cancer ≤ 2.5 cm, clearly visible on ultrasound and eligible for upfront surgery. All patients underwent ultrasound-guided cryoablation using a 2.4-mm cryoprobe, followed by standard surgical resection 14–28 days later. Complete ablation was defined as the absence of residual invasive or in situ carcinoma on final pathology. Secondary outcomes included imaging–pathology correlation and the association between tumor size, ice-ball dimensions, and ablation success.

Among 48 evaluable patients, the invasive complete ablation rate was 97.9%, with 100% success in tumors ≤ 2.0 cm on MRI. The complete ablation rate was 89.6%, increasing to 96.9% for tumors ≤ 2.0 cm and 100% for tumors ≤ 1.0 cm. Only one patient (2.1%) had residual invasive disease (3 mm). Residual ductal carcinoma in situ was observed in 12.5% of patients, with a mean size of 2.2 mm. Cryoablation was well tolerated, with one minor skin burn (2.1%) and no serious adverse events. MRI demonstrated high predictive accuracy for complete response (negative predictive value, 93.0%), whereas ultrasound and mammography were less accurate (negative predictive values, 9.3% and 34.9%, respectively). Ice-ball margins ≥ 1 cm beyond the tumor were associated with complete ablation in most cases.

Cryoablation achieved high rates of complete tumor ablation with an excellent safety profile, particularly in tumors ≤ 2.0 cm, in carefully selected patients with early-stage invasive breast cancer. These findings provide robust pathological and imaging validation of cryoablation as an effective ablative approach; however, they do not support its use as a standalone definitive therapy or, even when combined with adjuvant treatments such as radiotherapy and endocrine therapy, as a standard of care at this stage. As a phase II study, these results are not practice-changing and warrant confirmation in randomized phase III trials to evaluate long-term oncologic outcomes and to define the potential role of cryoablation within surgical de-escalation strategies.

ClinicalTrials.gov Identifier NCT05398497 (Registration date May 26, 2022).