Researchers are consistently pushing back the boundaries of what is possible for the treatment of breast cancer. Results of one of the most exciting and innovative trials in breast cancer, the ICE3 Trial on cryoablation of early stage, low-risk breast cancer, were recently published in the Annals of Surgical Oncology by Dr. Richard Fine. In the article titled, “Cryoablation Without Excision for Early–Stage Breast Cancer: ICE3 Trial 5–Year Follow–Up on Ipsilateral Breast Tumor Recurrence” the full study methodology and results – which report a recurrence free rate of 96.3% for women treated with cryoablation and endocrine therapy – are explained in full detail.
Here we will discuss how the ICE3 results might impact the future of breast cancer treatment and research.
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, thus offering new opportunities for a personalized patient management. With such advancements in breast cancer care, the time was ripe to explore innovative, minimally invasive 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 to investigate the safety and efficacy of liquid-nitrogen-based cryoablation for up to 1.5 cm, low-risk, early-stage malignant breast tumors without subsequent excision. Cryoablation uses extreme cold to destroy tumors by freezing. It is a minimally invasive treatment compared to surgery. A thin needle-like cryoprobe is inserted into a tumor under imaging guidance. The cryoprobe creates an ultra-cold, lethal ice ball around the target tissue. Essentially, the cancerous tumor and a 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 60 years or older with unifocal invasive ductal cancers measuring 1.5 cm 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.
All tumors had a 1- to 2-cm freeze margin past the tumor to ensure the complete ablation of tumor tissue. A cautious approach was taken to avoid thermal injury to the skin and chest wall, especially for patients with small breasts.
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 first presented at the ASBrS Annual Meeting in April 2024. Publication in the Annals of Surgical Oncology article brought the ICE3 trial results to a wider global audience with a positive response. 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 continues to gain interest and support
96.3% of participants in the subpopulation who received hormone therapy following cryoablation, were free from recurrence at their 5-year follow-up. The overall survival rate (including patients who did not receive hormone therapy) was 96.7%. 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.
No significant adverse effects or complications were reported in the final analysis of the 5-year study.
Satisfaction scores among both patients and physicians were overwhelmingly positive, with 100% satisfaction with the cosmetic results. Quality-of-life score demonstrated statistically significant improvement (p < 0.001) in distress level at 6 months as compared with baseline.
Public recognition for ICE3 results
Every year healthcare professionals and researches submit thousands of abstracts to scientific and medical conferences. The results of the ICE3 trial have received special recognition, inspiring researchers to conduct further investigation into breast cancer cryoablation. At the 2024 American Society of Breast Surgeons Conference, ICE3 investigator Dr. Richard Fine was awarded the prestigious Scientific Impact Award. The award was for his presentation “Cryoablation Without Excision for Early-Stage Breast Cancer; ICE3 Trial 5 Year Follow Up on Ipsilateral Breast Tumor Recurrence.” Fourteen submissions were chosen to make oral presentations, representing only 4% of submissions. From these submissions, the final winner of the prestigious Scientific Impact Award is selected based on audience ranking.
Co-Primary Investigator of the ICE3 Trial, Dr. Kenneth Tomkovich, received the European Society of Breast Imaging (EUSOBI) 2024 Abstract Award. This was for his submission “Image Guided Cryoablation as a Primary Treatment for Low-Risk Breast Cancers: Results and Imaging Findings of the ICE3 trial. Six other abstracts exploring different aspects of breast cancer and breast tumor cryoablation were presented. These included the THERMAC trial from the Netherlands, presented by Dr. Sophie Wooldrik. She was awarded with the EUSOBI Young Physician Scientist Competition. THERMAC compared the efficacy of minimally invasive ablative treatments including radiofrequency, microwave, and cryoablation.
The THERMAC Trial demonstrated cryoablation to have a 94% complete rate of ablation. This was compared to an ablation rate of 33% for radiofrequency and 73% for microwave. With no adverse events, cryoablation was the safest and most effective among the ablative methods used in the trial. 50% of study patients treated with radiofrequency experiencing mild to moderate adverse events. 40% of study patients treated with microwave experiencing mild to moderate adverse events.
A sign of things to come
The ICE3 trial results have sparked a growing interest in research dedicated to breast cancer cryoablation. This illustrates how eagerly this innovation is investigated by healthcare professionals. The potential of cryoablation as a viable minimally-invasive option for breast cancer patients is significant. Cryoablation offers a new choice and hope for patients.