As many readers know, I was diagnosed with breast cancer in 2018. Following extensive research, I chose to do cryoablation (cry-o-a-blay-shun), a minimally invasive procedure which freezes the tumor and was in clinical trials at City of Hope at the time. The therapy was successful for me and others, but with COVID, many facilities stopped offering the procedure. However, trials continued with Dennis Holmes, MD as a primary source of information and a lead advocate for women’s breast health.

As Dr. Holmes describes, cryoablation uses a small, needle-like cryoprobe and extremely cold temperatures to destroy cancer cells along with a margin of surrounding normal breast tissue—similar to the goals of a lumpectomy. Unlike traditional early stage 1 breast cancer treatment such as a lumpectomy, the 45-minute in-office procedure is performed under local anesthesia offering a faster recovery that enables patients to quickly resume daily activities. According to Holmes, studies on patient-reported outcomes have shown that cryoablation provides a greater sense of physical well-being, improved sexual well-being, and higher breast satisfaction compared to lumpectomy.

Many of us feel very strongly that cryoablation should become an acceptable standard of care for early stage breast cancers. Recently, Holmes shared an update on the current clinical trials which I am delighted to share as reported.

The ICE3 Trial. In September 2024, the 5-year follow-up results of the ICE3 Trial were published in the Annals of Surgical Oncology. The study demonstrated cryoablation to be as safe and effective as lumpectomy for many women with early-stage breast cancer.

The ICE3 Trial was a multicenter, single-arm, non-randomized clinical study designed to evaluate cryoablation as an alternative to lumpectomy. It enrolled 194 women, aged 55 to 94 years (mean age 75), with clinical stage I invasive ductal carcinoma measuring ≤1.5 cm by mammography and ultrasound. Eligible tumors were histologic grade 1 or 2, estrogen receptor (ER) positive, progesterone receptor (PR) positive, and HER2/neu negative, as confirmed by needle biopsy.

The trial did not mandate the use of anti-estrogen or radiation therapy, or sentinel node biopsy. However, nearly 80% of participants received anti-estrogen therapy, 14% received radiation therapy and only 8% had sentinel node biopsies. After 5 years of follow-up, there were 7 cases of cancer recurrence in the same breast, resulting in a local recurrence rate of 4.7%. Among the 124 participants who received anti-estrogen therapy, the local recurrence rate was even lower at 3.7%.

These low recurrence rates in ICE3 closely mirror results from other clinical trials that did not use cryoablation, but evaluated traditional care lumpectomy plus anti-estrogen therapy without radiation. Recurrent breast cancer rates from LUMINA (2.3%), IDEA (3.5%) and PRIME II (4.1%) trials are similar to ICE3, which support cryoablation as a safe and effective alternative to lumpectomy for women meeting the criteria.

The FROST Trial. The Freezing Instead of Removal Of Small Breast Tumors (FROST) Trial is a multicenter, non-randomized clinical trial designed and led by Holmes. Beginning in 2016, the trial enrolled 82 women with clinical stage I invasive ductal carcinoma (tumor extended outside of milk ducts) measuring ≤2.0 cm, as determined by mammography, ultrasound and/or contrast-enhanced MRI. All tumors were ER positive, PR positive, and HER2/neu negative, as confirmed by needle biopsy.

The trial included two treatment arms: 1) Women aged 50–69 were required to receive radiation therapy, a sentinel node biopsy and anti-estrogen therapy;
2) Women aged 70 and older were only required to take anti-estrogen therapy.

The mean patient age was 75.6 years (range: 56–94 years). At a follow-up of 6.5 years, only
3 recurrences were reported yielding a 3.6% local recurrence rate—a rate that is comparable to lumpectomy outcomes in similar clinical trials. There were no breast
cancer-related deaths.

The FROST Trial’s findings reinforced results from the ICE3 Trial, suggesting that women over 70 may safely omit radiation therapy and sentinel node biopsy following cryoablation, provided they are willing to take anti-estrogen therapy. Furthermore, the FROST Trial may begin to pave the way for the expanded use of cryoablation in women under 60, offering a promising alternative treatment approach for this population.

Long-term follow-up of all trial participants is ongoing and a full report of the FROST Trial is expected to be published this year.

DCIS Cryoablation Trial. “Nearly every invasive breast cancer begins as DCIS which is commonly referred to as pre-invasive or non-invasive breast cancer,” Holmes explains. “If not for the risk of progression to invasive cancer, the treatment of DCIS would be entirely unnecessary.”

In 2023, he launched the DCIS Cryoablation Trial as a single-center clinical study investigating cryoablation as an alternative to lumpectomy to prevent the progression of DCIS to invasive breast cancer.

Participation in the trial is currently open to women aged 18 and older who have a core needle biopsy diagnosis of grade I–III DCIS, measuring <2 cm based on mammography, ultrasound and breast MRI (if performed). In this study, the use of anti-estrogen therapy and radiation therapy is optional. To date, none of the study participants has experienced a recurrence at their original cancer site.

A few open slots remain in this ongoing trial. The study is open to women across the U.S. and requires just one in-person visit to Los Angeles. Treatment administered as part of the trial is free of charge, and Holmes generously volunteers his time to treat study participants.

Status of FDA approval of cryoablation technology

In November of last year, the FDA General and Plastic Surgery Devices Panel of the Medical Devices Advisory Committee convened to evaluate whether the committee should recommend FDA approval for the IceCure ProSense^™ Cryoablation System, the medical device used in the ICE3 trial. After a 9-hour review of safety and effectiveness data, the panel voted in favor of recommending FDA approval as a treatment option for women aged 60 years and older with stage I, low- or intermediate-grade, ER+, PR+, HER2/neu-negative invasive ductal breast cancer, measuring ≤1.5 cm—the exact group studied in the ICE3 Trial.

While the panel’s affirmative vote does not guarantee final FDA approval, its recommendation plays a critical role in the FDA’s decision-making process. An official FDA decision is anticipated in the spring of 2025. It is expected that FDA approval could ultimately lead to insurance coverage for the procedure which is currently out-of-pocket pay for non-trial participants.

For more information on these trials and to receive updates from Dennis Holmes, MD, visit www.cryoablation.com. For more on Lauren’s personal journey, visit
www.deserthealthnews.com/health-categories/laurens-cancer-journey.

Source: 1) L.A. Breast Chronicles, Dennis R. Holmes, MD, FACS, December 24, 2024.