Percutaneous Cryoablation for the Treatment of Breast Cancer

CRYSTAL is a prospective, single-center, single-arm interventional study evaluating ultrasound-guided percutaneous cryoablation for the treatment of selected patients with localized breast cancer.

The study includes two clinical cohorts. Cohort A includes patients with localized breast cancer who are not suitable candidates for surgery because of age, comorbidities, or other clinical factors, as well as patients who decline surgery after appropriate multidisciplinary evaluation and counseling. Cohort B includes selected postmenopausal patients with small, unifocal, biologically low-risk breast cancers considered suitable for a minimally invasive treatment strategy.

All participants will have histologically confirmed breast cancer before treatment, with assessment of relevant prognostic and predictive tumor markers. Eligibility and treatment strategy will be discussed within the multidisciplinary breast unit.

Cryoablation will be performed percutaneously under ultrasound guidance. The procedure will aim to obtain complete coverage of the tumor by the ice ball with an appropriate safety margin while protecting the skin, chest wall, and other adjacent structures.

Participants will undergo clinical and imaging surveillance after treatment. Ultrasound and contrast-enhanced mammography (CEM) will be the principal imaging techniques used to assess the ablation area and detect possible residual or recurrent disease. Breast magnetic resonance imaging may be used when CEM is contraindicated, not feasible, or inconclusive. Tissue sampling will be performed when clinical or imaging findings are suspicious or inconclusive.

The primary objective is to evaluate complete local tumor ablation approximately 6 months after cryoablation. Secondary objectives include technical success, procedure-related adverse events, residual disease, need for repeat cryoablation or subsequent surgery, procedural characteristics, quality of life, and local recurrence during follow-up.

Adjuvant systemic treatment and/or radiation therapy will be administered when clinically indicated according to multidisciplinary assessment and standard clinical practice. Participants will be followed for up to 24 months after cryoablation.

Inclusion criteria

General criteria:

• Female participants aged 18 years or older.
• Histologically confirmed invasive breast carcinoma diagnosed by core needle biopsy.
• Unifocal and unilateral tumor.
• Tumor clearly visible and accessible by ultrasound.
• Tumor considered technically suitable for ultrasound-guided cryoablation, with the possibility of achieving adequate ice-ball coverage and safety margins.
• No known distant metastatic disease.
• Ability to understand the study procedures and provide written informed consent.

Cohort A:

• Participants considered unsuitable for breast surgery because of age, comorbidities, or other clinical conditions, or participants who decline surgical treatment after appropriate multidisciplinary evaluation.

Cohort B:

• Postmenopausal participants with early-stage, low-risk invasive breast cancer.
• Invasive tumor preferably 15 mm or smaller.
• Hormone receptor-positive (estrogen receptor and/or progesterone receptor positive).
• HER2-negative.
• Histological grade 1 or 2.
• Clinically node-negative disease.
• Invasive carcinoma of no special type or another favorable low-risk histological subtype

Exclusion criteria

• Multifocal or multicentric breast cancer.
• Bilateral breast cancer requiring treatment.
• Tumor not adequately visible or accessible by ultrasound.
• Tumor location or anatomy preventing safe cryoablation or achievement of an adequate ablation margin.
• Known distant metastatic disease.
• HER2-positive invasive breast cancer for Cohort B.
• Predominantly extensive intraductal disease or other findings considered unsuitable for cryoablation.
• Contraindication to the planned cryoablation procedure.
• Inability to provide informed consent or comply with study follow-up.