Stereotactic Guided Biopsy and Cryoablation

Stereotactic Guided Biopsy and Cryoablation of Breast Cancer

The purpose of this study is to evaluate a new strategy to treat small breast cancer called cryoablation, or cryosurgery, in combination with biopsy methods which are guided by certain imaging like mammography.

Study Overview

• Status: Withdrawn
• Conditions: Breast Cancer
• Intervention / Treatment: Device: Stereotactic Guided Biopsy and Cryoablation

Detailed Description

For participants who choose to enroll in this study, the doctor will perform an excisional biopsy to remove the tumor (a biopsy to attempt to remove the whole tumor), after which a clip will be placed. Using the clip as a guide, the doctor will then cryoablate the biopsy cavity. Cryoablation is a kind of treatment that uses a hollow, thin tube, called a cryoprobe, to kill any residual tumor by freezing it. By conducting this study, the research team will investigate whether biopsy followed by cryoablation guided by mammography will prove to be an effective and safe way of treating breast cancers. It is anticipated that participation in this research will last about 2 years.

• Study Type: Interventional
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age 60 years or older, European Cooperative Oncology Group (ECOG) score 0-2
• Lesion size 1.0 cm or smaller in greatest diameter. The largest diameter will be determined at the time of the diagnostic work up. For targets that are imaged in multiple modalities the largest diameter will prevail in determining eligibility. Note- 1.0 cm target size is chosen since extent may be underestimated upon initial diagnosis.
• Biopsy proven DCIS, (including any lesion with DCIS +/- IDC)
• Closest margin of target to the skin >15 mm
• Compressed breast thickness to > 55mm
• Unifocal primary disease (Patients with contralateral disease will remain eligible.)
• Able to provide consent

Exclusion Criteria:

• Multifocal or multicentric disease within the breast.
• Prior surgical biopsy for diagnosis or treatment of index lesion.
• Patients not suitable for stereotactic biopsy/cryoablation technique according to treating physician.
• Patients receiving neoadjuvant therapy.
• History of previously treated ipsilateral or contralateral breast carcinoma is not an exclusion criterion if the investigator is certain newly diagnosed carcinoma is a new unifocal primary tumor.
• High-risk pathology (e.g., Grade 3, HER2+ status, Genomic high-risk score (if available)).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Cryoablation

Device: Stereotactic Guided Biopsy and Cryoablation; Treatment of the lesion through a three-step procedure: 1) Tomosynthesis-guided stereotactic biopsy of the target (minimum 12 cores) which would include the initial tissue marking clip placed at time of initial diagnostic biopsy, then biopsy of the surrounding tissue using the same fixed sheath (minimum 12 cores) to allow for a better pathologic evaluation of extent of the target Ductal Carcinoma In Situ (DCIS). 2) Immediate cryoablation of biopsy site/cavity performed through the same sheath. 3) four post cryoablation biopsies through the same sheath to evaluate for any residual disease.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall feasibility	Overall feasibility will be defined as study procedure completeness in more than 90% of enrolled patients AND data completeness in more than 90% of enrolled patients.	Up to 5 Years
Feasibility - Procedure Completeness	Study procedure completeness feasibility will be defined as the patient's ability to tolerate the entire single procedure consisting of stereotactic biopsy of central target & surrounding tissue + cryoablation of biopsy site/cavity + stereotactic biopsy (through the same sheath) of the post-cryoablation cavity. Study procedure completeness feasibility will be considered to have been met if > 90% of enrolled patients complete the procedure.	Within 1 month post procedure (+/- 7 days)
Feasibility - Data Completeness	Data completeness feasibility will be defined as the ability to complete data collection from patients on study procedure, adverse events, follow-up imaging assessment, and tumor recurrence assessment elements. Data completeness feasibility will be considered to be met if these elements are collected in > 90% of enrolled patients.	Up to 5 Years
Study Safety	Study safety will be defined as ≤ 10% of patients having experienced serious adverse events that are either possibly or definitely related to the 3-step procedure (i.e., ≤ 2 patients in the entire study) AND ≤ 15% of patients experiencing moderate or severe adverse events (i.e., the Common Terminology Criteria for Adverse Events v 5.0) (CTCAE) Grades 3-5 that are either possibly or probably related to the 3-step procedure (i.e., ≤ 3 patients in the entire study). For purposes of this study, cancer recurrence will be identified as a serious adverse event due to its life-threatening nature. All patients that begin the 3-step procedure will be included in the safety analysis.	Day of procedure and within 1-month post-procedure (+/- 7 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility Outcomes - Removal of biopsy clip	Removal of the cryoablation biopsy clip from the central target lesion will be analyzed as the proportion of patients who had clip removed relative to all patients who participated in the study. Successful targeting and removal of the cryoablation biopsy clip in ≥ 90% of patients who participated in the study is the threshold for this feasibility outcome.	Within 1 month post procedure (+/- 7 days)
Feasibility Outcomes - Negative margins	Negative (clean) margins will be defined as no tumor seen in the surrounding tissue by pathological evaluation following the procedure. Negative margins will be analyzed as the proportion of patients with negative margins relative to all patients who participated in the study. Negative margins (as determined by biopsies of surrounding tissue upon pathological assessment) observed in ≥ 90% of patients who participate in the study is the threshold for this feasibility outcome.	Within 1 month post procedure (+/- 7 days)
Feasibility Outcomes - Local recurrence	Local recurrence will be defined as evidence of invasive or in situ breast cancer in the ipsilateral breast or chest wall. Patients who develop clinical evidence of tumor recurrence in the remainder of the breast or chest wall will be recommended to have a biopsy of the suspicious lesion to confirm the diagnosis. If a biopsy is not performed for any reason, an imaging designation of BIRADS 4 and 5 will be considered evidence of disease recurrence. Given the challenges of reliably defining local recurrence vs. new primary, all recurrences in the ipsilateral breast will be considered in the analysis of local recurrence. Local recurrence will be evaluated in patients for 5 years after study procedure using Kaplan-Meier methods.	6 months, 12 months, 18 months, 24 months, 36 months, 48 months, and 60 months
Patient satisfaction questionnaire - time	Patient satisfaction related to the time necessary to complete the procedure will be evaluated via administration of a questionnaire. Patients will be asked to rate satisfaction of the time needed based on a 5-point scale ranging from 1 ("Very Dissatisfied") to 5 ("Very Satisfied"), such that higher scores are indicative of better satisfaction with the time needed to complete the procedure.	Within 7 days of procedure
Procedural Pain - questionnaire	Pain associated with the procedure will be evaluated via administration of a questionnaire. Patients will be asked to rate pain associated with the procedure based on a 6-point scale ranging from 1 ("No pain") to 5 ("Worst pain possible"), such that lower scores are indicative of less pain severity in association with the procedure.	Within 7 days of procedure
Procedural symptoms - questionnaire	Symptom severity associated with the procedure will be evaluated via administration of a questionnaire. Patients will be asked to rate the severity of their symptoms using a 4-point scale ranging from 1 ("Mild") to 4 ("Very Severe"), such that lower scores are indicative of less symptom severity associated with the procedure.	Within 7 days of procedure
Patient satisfaction with breasts - preoperatively	Patient satisfaction with breasts prior to treatment will be evaluated using Version 2.0 of the Breast-Q 'Satisfaction with Breasts' module. The preoperative Breast-Q module consists of 4 questions which asks patients to describe how satisfied/dissatisfied they have been over the past week with their breasts. The 4 responses are rated using a 4-point scale ranging from 1 ("Very Dissatisfied") to 4 ("Very Satisfied"), yielding a raw sum score of 4-16. Raw Breast-Q sum scores are then converted using a validated "Equivalent Rasch Transformed Score" table ranging from 0-100 such that higher Rasch scores are indicative of a better outcome. If missing data comprises <50% of the scale's items, the mean of the missing items is inserted into the table.	Within 7 days of procedure
Patient satisfaction with breasts - postoperatively	Patient satisfaction with breasts and breast cancer treatment prior following the procedure will be evaluated using Version 2.0 of the Breast-Q breast cancer treatment (BCT) module. This Breast-Q module consists of 11 questions which ask patients to describe how satisfied/dissatisfied they have been over the past week with respect to their breasts and breast cancer treatment. The 11 responses are rated using a 4-point scale ranging from 1 ("Very Dissatisfied") to 4 ("Very Satisfied"), yielding an overall sum score of 11-44. Raw Breast-Q sum scores are then converted using a validated "Equivalent Rasch Transformed Score" table ranging from 0-100 such that higher Rasch scores are indicative of a better outcome. If missing data comprises <50% of the scale's items, the mean of the missing items is inserted into the table.	Within 7 days of procedure and within 1 year (+/- 1 month) post procedure

Collaborators and Investigators

• Sponsor: Montefiore Medical Center
• Investigators: Principal Investigator: Laura A Hodges, MD, Montefiore Medical Center

Publications and helpful links

General Publications

• Farante, G., et al., Advances and controversies in management of breast ductal carcinoma in situ (DCIS). Eur J Surg Oncol, 2022. 48(4): p. 736-741.
• Cowell, C.F., et al., Progression from ductal carcinoma in situ to invasive breast cancer: revisited. Mol Oncol, 2013. 7(5): p. 859-69.
• Sheaffer, W.W., et al., Predictive factors of upstaging DCIS to invasive carcinoma in BCT vs mastectomy. Am J Surg, 2019. 217(6): p. 1025-1029.
• Wapnir, I.L., et al., Long-term outcomes of invasive ipsilateral breast tumor recurrences after lumpectomy in NSABP B-17 and B-24 randomized clinical trials for DCIS. J Natl Cancer Inst, 2011. 103(6): p. 478-88.
• Sabel, M.S., et al., Cryoablation of early-stage breast cancer: work-in-progress report of a multi-institutional trial. Ann Surg Oncol, 2004. 11(5): p. 542-9.
• Erinjeri, J.P. and T.W. Clark, Cryoablation: mechanism of action and devices. J Vasc Interv Radiol, 2010. 21(8 Suppl): p. S187-91.
• Ward, R.C., A.P. Lourenco, and M.B. Mainiero, Ultrasound-Guided Breast Cancer Cryoablation. AJR Am J Roentgenol, 2019. 213(3): p. 716-722.
• Truesdale, M.D., et al., Comparison of two core biopsy techniques before and after laparoscopic cryoablation of small renal cortical neoplasms. JSLS, 2011. 15(4): p. 509-16.
• Fine, R.E., et al., Cryoablation Without Excision for Low-Risk Early-Stage Breast Cancer: 3-Year Interim Analysis of Ipsilateral Breast Tumor Recurrence in the ICE3 Trial. Ann Surg Oncol, 2021. 28(10): p. 5525-5534.
• Hughes, K.S., et al., Lumpectomy plus tamoxifen with or without irradiation in women 70 years of age or older with early breast cancer. N Engl J Med, 2004. 351(10): p. 971-7.
• Kunkler, I.H., et al., Breast-conserving surgery with or without irradiation in women aged 65 years or older with early breast cancer (PRIME II): a randomised controlled trial. Lancet Oncol, 2015. 16(3): p. 266-73.
• Grimm, L.J., et al., Ductal Carcinoma in Situ: State-of-the-Art Review. Radiology, 2022. 302(2): p. 246-255.
• Strom, C., L.S. Rasmussen, and F.E. Sieber, Should general anaesthesia be avoided in the elderly? Anaesthesia, 2014. 69 Suppl 1(Suppl 1): p. 35-44.
• Poullain, F., et al., Percutaneous cryoablation of osteoblastoma in the proximal femur. Skeletal Radiol, 2020. 49(9): p. 1467-1471.
• Ushijima, Y., et al., Diagnostic accuracy of percutaneous core biopsy before cryoablation for small-sized renal cell carcinoma. Diagn Interv Radiol, 2023. 29(6): p. 800-804.
• Poplack, S.P., et al., A Pilot Study of Ultrasound-Guided Cryoablation of Invasive Ductal Carcinomas up to 15 mm With MRI Follow-Up and Subsequent Surgical Resection. AJR Am J Roentgenol, 2015. 204(5): p. 1100-8.
• Littrup, P.J., et al., Cryotherapy for breast cancer: a feasibility study without excision. J Vasc Interv Radiol, 2009. 20(10): p. 1329-41.
• Holmes, D. and G. Iyengar, Breast Cancer Cryoablation in the Multidisciplinary Setting: Practical Guidelines for Patients and Physicians. Life (Basel), 2023. 13(8).

Study record dates

Study Major Dates

• Study Start (Estimated): October 1, 2025
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2027

Study Registration Dates

• First Submitted: September 16, 2025
• First Submitted That Met QC Criteria: February 24, 2026
• First Posted (Actual): February 27, 2026

Study Record Updates

• Last Update Posted (Actual): February 27, 2026
• Last Update Submitted That Met QC Criteria: February 24, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: cryoablation
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms; Surgical Procedures, Operative; Ablation Techniques; Cryosurgery
• Other Study ID Numbers: 2025-17267

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes