Cryoablation for small breast tumors (SIX)

Cryoablation Versus Breast Surgery in the Local Treatment of Early-Stage Breast Cancer - Six Trial

This study will test whether cryoablation works as well as standard breast surgery for people with small (≤2.0 cm), unifocal early-stage breast cancer and will compare direct costs over one year.

Quick facts

• Phase: PHASE3
• Study type: Interventional
• Enrollment: 750 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Hospital do Coracao (other)
• Locations: 2 sites (São Paulo, São Paulo and 1 other locations)
• Trial ID: NCT06839001 on ClinicalTrials.gov

What this trial studies

This is a Phase 3 randomized non-inferiority trial comparing percutaneous cryoablation to standard breast surgery (lumpectomy or mastectomy) for T1N0M0 unifocal invasive breast cancer. The primary endpoint is locoregional control and non-inferiority of cryoablation over five years, with a one-year cost-minimization analysis of direct treatment costs. Secondary measures include one-year locoregional recurrence, five-year disease-free and overall survival, serial circulating tumor cell (CTC) monitoring, patient satisfaction (Breast-Q) at one year, and quality of life (EQ-5D). The protocol incorporates a de-escalated approach by omitting sentinel lymph node biopsy when appropriate, using ultrahypofractionated radiotherapy, and applying liquid biopsy for monitoring.

Who should consider this trial

Good fit: Ideal candidates are people with a single invasive breast tumor ≤2.0 cm that is visible on ultrasound, clinically node-negative, without skin involvement, no prior neoadjuvant therapy, and who would otherwise be surgical candidates.

Not a fit: Patients with multifocal or multicentric disease, ductal carcinoma in situ alone, clinically positive axilla, tumor-to-skin distance <5 mm, prior neoadjuvant therapy, or distant metastases are unlikely to benefit from this approach.

Why it matters

Potential benefit: If successful, cryoablation could offer a less invasive, outpatient alternative to surgery with faster recovery and lower direct costs while preserving similar oncologic outcomes.

How similar studies have performed: Small nonrandomized and pilot studies have reported promising local control with cryoablation for small breast cancers, but randomized Phase 3 evidence comparing it directly to surgery is limited.

Eligibility criteria

Inclusion Criteria:

* Unifocal primary invasive breast carcinoma
* Tumor size ≤ 2.0 cm (T1)
* Complete pathological report (including results for ER, PR, HER2, Ki-67, and FISH report for the ERBB2 gene, if necessary)
* Lesion visible on ultrasound
* Surgical treatment would be the first option, regardless of immunohistochemistry results

Exclusion Criteria:

* Multifocal or multicentric invasive breast carcinoma
* Ductal carcinoma in situ
* Breast cancer with skin involvement
* Clinically positive axilla (N1, N2 or N3)
* Distance from lesion and skin less than 5 mm
* Prior neoadjuvant systemic therapy for breast cancer
* Distant metastasis

Where this trial is running

São Paulo, São Paulo and 1 other locations

• Research Institute - Hospital do Coracao — São Paulo, São Paulo, Brazil (NOT_YET_RECRUITING)
• Research Institute - Hospital do Coracao — São Paulo, São Paulo, Brazil (RECRUITING)

Study contacts

• Principal investigator: Vanessa Monteiro Sanvido, PhD — Research Institute - Hospital do Coracao
• Study coordinator: Vanessa Monteiro Sanvido, PhD, Professor

Conditions: Breast Cancer, Breast Neoplasm, Minimally Invasive Surgical Procedures, Cryoablation, Locoregional Recurrence, Cost-Minimization Analysis