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A step forward towards cryoablation for early-stage breast cancer: Final 5-year results of the ICE3 trial

two women embracing after cryoablation breast cancer treatment

Researchers are consistently pushing back the boundaries of what is possible in terms of breast cancer treatment, early detection, and prevention. One of the most exciting and innovative trials in breast cancer, the ICE3 Trial on cryoablation of early stage, low-risk breast cancer, announced its final 5-year results at the American Society of Breast Surgeons (ASBrS) conference in April 2024.  

Here we share the results of the ICE3 trial and how this study results might impact breast cancer treatment and research in the future.  


Opportunity for innovation in breast cancer treatment 

Our understanding of breast cancer has grown dramatically in recent decades. Advances in breast imaging, and new recommendations for breast cancer screening to begin at a younger age and more frequently have allowed for earlier diagnosis. Progress in genomics has given a clearer picture of tumor prognosis, which in turn is opening new opportunities for a personalized approach to patient management. With earlier detection of breast cancer and the identification of patients who may benefit from a minimally invasive approach and adjuvant therapies, the time was ripe to explore innovative approaches, such as cryoablation. 


The ICE3 Study on Cryoablation of Small, Low-Risk Breast Cancer

The ICE3 trial was the largest multi-center clinical trial investigating the safety and efficacy of liquid-nitrogen- based cryoablation system for up to 1.5 cm (about 0.59 in), low-risk, early-stage malignant breast tumors without subsequent excision. Cryoablation uses extreme cold to destroy tumors by freezing and is a minimally invasive treatment compared to surgery. During a cryoablation procedure, a thin needle-like cryoprobe is inserted into a tumor under imaging guidance to create an ultra-cold and lethal ice ball around the target tissue. Essentially, the cancerous tumor and margin around it is destroyed (ablated) by freezing.  

The ICE3 trial was designed to explore the potential for cryoablation to safely and effectively treat women aged 60 and over with early-stage breast cancer, allowing them to avoid the associated risks of surgery, such as the need for general anesthesia, infection, and risk of re-excision. Ipsilateral breast tumor recurrence (IBTR), a local recurrence of treated tumor was the primary outcome. The choice of appropriate adjuvant treatment was left to the discretion of the treating physician.  

Women over 60 years or older with unifocal invasive ductal cancers measuring 1.5 cm (about 0.59 in) or less were eligible for inclusion in the trial. All tumors were low-grade, Hormone Receptor Positive (HR+), Human Epidermal Growth Factor Receptor 2 Negative (HER2-), consistent with a low-risk form of breast cancer. 

Breast size had to allow for a margin of 1 cm from lesion to skin, to ensure safe cryoablation. The trial began in 2014 with recruitment from 19 prestigious hospitals and medical centers across the US. 194 eligible patients received cryoablation per protocol and were included in the statistical analysis. 

ICE3 trial protocol 

Patients were treated with a cryoablation freeze-thaw-freeze cycle for 9, 8, 9 minutes, respectively, using the ProSense™ Cryoablation System and a 3.4 mm cryoprobe, according to standard system operating instructions.  

Patients were followed at 6 months, 1 year, and annually after that, for 5 years with clinical and imaging assessments. In addition to potential tumor recurrence, patient and physician satisfaction with cosmetic results and distress tool were also evaluated.  

The results of the ICE3 trial

The last patient completed their 5-year follow up in early 2024. Final trial results received an enthusiastic reception when they were presented at the ASBrS Annual Meeting in April 2024.  

The potential for a liquid nitrogen- based cryoablation system to offer a viable minimally-invasive alternative to standard of care lumpectomy to this patient population was resoundingly supported.  

96.3% of participants in the subpopulation who received hormone therapy following cryoablation, were free from recurrence at their 5-year follow-up. This was in line with the results of the LUMINA study, which found a 97.7% recurrence free rate in patients who received lumpectomy together with hormone therapy and the PRISMA meta-study, which included Lumina, reporting a 97.19% recurrence free rate at 5-year follow up.  

In the final analysis of the 5-year study, no significant adverse effects or complications were reported.  

Satisfaction scores among both patients and physicians were overwhelmingly positive, with 100% satisfaction with the cosmetic results.  

ASBrS Scientific Impact Award 

Every year, of the hundreds of abstracts submitted to the ASBrS conference, 14 are chosen to make oral presentations (in 2024, this represented only 4% of submissions) from which the final winner of the prestigious Scientific Impact Award is chosen based on audience ranking. Thanks to the groundbreaking findings of the ICE3 trial, the prize was awarded to ICE3 investigator Dr. Richard Fine, for his submission titled “Cryoablation Without Excision for Early-Stage Breast Cancer; ICE3 Trial 5 year follow up on Ipsilateral Breast Tumor Recurrence.”  

A sign of things to come 

The high interest in the ICE3 trial results at the recent ASBrS conference is a sign of how eagerly this innovation is awaited by breast surgeons. The potential of cryoablation as a viable minimally-invasive alternative for breast cancer patients is significant, offering new choice for providers and new hope for patients.