Published online May 2002

Introduction:

The treatment of breast cancer through the majority of the twentieth century was the radical mastectomy; the removal of the entire breast, the overlying skin, the underlying muscles and all of the lymph nodes underneath the arm. This operation was very disfiguring, had significant side effects, and while it prevented local recurrence (the chance of the cancer returning on the chest wall), it failed to cure many patients. Since that time, the treatment of breast cancer has shifted away from mastectomy and towards removing just the cancer, leaving the normal breast tissue intact. It was discovered that following a lumpectomy (where just the tumor is removed with a margin of normal tissue) with radiation to the breast resulted in a low rate of local recurrence, almost as low as with a mastectomy. This led to a very large study in the United States involving nearly 2000 women that demonstrated that a lumpectomy plus radiation was equivalent to a mastectomy. These results were verified by trials around the world, and in 1990 the National Institutes of Health recommended that breast-conservation therapy was the appropriate method of primary surgery for most women with early breast cancer. The importance of breast conservation as an alternative to mastectomy has grown dramatically as more women have tumor detected at a smaller size with the increased use of screening mammography.
Advances in imaging, such as digital mammography, ultrasound and magnetic resonance imaging (MRI) have improved our ability to both visualize smaller breast tumors and biopsy them without the need for surgery. This is known as a stereotactic biopsy. The next logical step in the treatment of breast cancer is the ability to treat tumors in a similar manner, without the need for surgical resection. Lumpectomy, while significantly better than mastectomy, can still leave a cosmetic defect and requires a trip to the operating room. Several new techniques are being studied where a probe is placed through a small incision in the skin, into the center of a tumor, and used to destroy all of the breast cancer cells by either heating or freezing them. This is referred to as in situ ablation. Some methods for ablation can potentially destroy the cancer cells from the outside, without even the need to place a probe through a skin incision. Early studies have shown that these techniques can be performed without sedation, with minimal to no discomfort to the patient and very few side effects. More importantly, they can completely destroy the tumor while leaving the remainder of the breast intact, resulting in excellent cosmetic results. This article will describe some of the techniques being used to destroy tumors in the breast. However, it is important to stress that all of these approaches are experimental, and there is minimal experience to date with them. The standard of care for breast cancer is still surgical resection, and no woman should be treated by any of these methods outside of a research study. Hopefully, however, if enough women agree to participate in this research, in situ ablation may soon replace lumpectomy as the treatment for early-stage breast cancer.

Radiofrequency Ablation:

Radiofrequency ablation (RFA) delivers an electrical current to the tumor tissues, which causes them to vibrate rapidly and create frictional heating. Using ultrasound, a surgeon can place a probe at the center of a tumor, and then small prongs are deployed around it (like an umbrella). The probe is connected to a generator and the electrical current raises the temperature at the site to 95 degrees Celcius and maintained for about 15 minutes. This is used quite commonly in the treatment of tumors in the liver, and is now being studied in the breast. Several studies are ongoing at the University of Texas MD Anderson Cancer Center, Weill Cornell Breast Center and John Wayne Cancer Institute where women with breast cancer underwent destruction of their tumors by RFA and then had standard surgery. The patients tolerated the procedure very well, with very few side effects. When they looked at the tissue after surgical resection, almost all the tumors had been completely destroyed by RFA. Plans are underway to begin a study at MD Anderson Cancer Center where breast cancers are ablated with RFA followed by radiation therapy without surgical resection.

Laser Therapy:

Lasers can also be used to heat and destroy tumors while still in the breast. A fiberoptic cable can be placed within a tumor using either stereotactic guidance (similar to when a biopsy is performed) or MRI. At the tip of the cable is a diffusing quartz. Light energy from the laser is passed through the cable and the resulting heat can destroy a sphere surrounding tissue around the laser tip. The amount of laser energy needed to be sure to destroy the tumor can be calculated based on size of the tumor, including a 0.5 cm margin of normal breast tissue. The procedure has been performed safely with minimal pain. Like with RFA, after the breast cancers were destroyed by laser, they were surgically resected and examined by a pathologist. Complete destruction of the tumor was shown in a majority of patients, however several patients had breast cancer cells that were still present at the time of surgery. Research is ongoing at Rush-Presbyterian-St. Luke’s Hospital and the University of Arkansas to improve the ability of laser ablation to destroy 100% of tumors.

Cryosurgery:

As opposed to radiofrequency ablation or laser therapy, which use heat to destroy tumors, cryosurgery utilizes freezing temperatures to destroy cancer cells. Cryosurgery has actually been looked at as a method to treat advanced breast cancers for many years. Likewise, it has been a standard method of treating skin lesions. Advances in technology, specifically the development of a thin probe that can freeze lesions deeper in the body, has paved the way for cryosurgery to be used to treat cancers in the liver or prostate. It is also be studied as a method to treat early stage breast cancers. Using ultrasound guidance, a cryoprobe- essentially a large needle with a tip that gets extremely cold- is placed into the lesion (see Figure 1).

Typically the tumor is frozen, thawed, and then frozen again before removing the probe. Studies where cryosurgery was performed followed by surgical resection have shown that complete tumor death could be obtained when small tumors were frozen in this method. In addition to the excellent cosmetic results seen with cryosurgery, there is some evidence that freezing tumors can stimulate the immune system to destroy cancer cells elsewhere in the body. If this is true, then cryosurgery may hold benefits beyond destruction of the local tumors. Ongoing studies at The University of Michigan are examining both the feasibility of cryosurgery to completely destroy early stage breast cancers and stimulate an immune response.

Focused Ultrasound and Microwave Thermotherapy:

Radiofreqency, laser and cryoablation all require the placement of a probe within the tumor to achieve their results. Therefore they are referred to as “minimally invasive.â€ÂÂ� Newer technologies are being investigated for the treatment of breast cancer that are truly non-invasive. This means that no probe needs to placed into the center of the tumor, but rather the tumors can be heated from outside the breast.
One method for doing this is called high-intensity focused ultrasound (FUS). When used for imaging, ultrasound consists of a wide field of high-frequency sound waves being bounced off the tissues in your body. However when these ultrasound beams are focused intensely at one spot, they can heat the tissues. Early trials have shown this method can be used to treat early stage breast cancers with impressive results. For women with breast cancer, several transducers placed around the breast deliver high intensity focussed ultrasound to heat the tumor while other transducers use ultrasound to guide and monitor the process. With the improved three-dimensional soft tissue imaging of MRI, other researchers are finding they can very accurately destroy tumors with FUS while allowing for minimal destruction of normal tissue. FUS is presently being studied at the Brigham and Women’s Hospital in Boston and at the University of Texas MD Anderson Cancer Center.
Another truly non-invasive method for the in situ ablation of breast cancer is Focused Microwave Thermotherapy (FMT). Based on technology originally developed to detect and destroy an enemy missile (known as the Strategic Defense Initiative or the Star Wars plan), it was discovered that this technology could also be used to treat cancer cells. This technology takes advantage of the difference in water content between normal cells and cancer cells. Patients lie on their stomachs and place their breast through a hole in the table. FMT can then be used to heat tumors without burning the skin. Both focused ultrasound and microwave thermotherapy are new technologies, and much more research is necessary to determine if breast cancers can effectively be treated in this manner. However, early results are promising and ongoing research is being done at Columbia Hospital in Florida, UCLA Medical Center and Massachusetts General Hospital.

Future Directions:

In situ ablation holds tremendous potential as a treatment for early-stage breast cancer. Early studies have shown that each of the methods discussed can be performed safely, with little discomfort to the patient and minimal side effects. After being destroyed, the dead tissue is absorbed by the body, leaving a normal appearing breast without a scar. The procedures can usually be done without intravenous sedation, so many women could potentially be treated in the office without the need for a trip to the operating room. This would greatly improve the cost and convenience of breast cancer treatment.
However, it is important to stress that these are experimental therapies, and many questions still exist. When removing a tumor surgically, the pathologist can tell the surgeon if he or she has removed the entire tumor (“negative marginsâ€ÂÂ�). The surgeon can go back and remove more tissue if necessary. When the tumor is destroyed in place, without surgical excision, new methods are necessary to determine afterwards if the entire tumor has been destroyed. In addition, there is not enough known about how these procedures may affect subsequent mammograms. This may make it difficult to look for recurrences in the years after treatment. Additional research is necessary to answer these questions.
It is also important to bear in mind that surgery is still the “gold standardâ€ÂÂ� for the treatment of breast cancer, and for cancers detected at an early stage, the results are excellent. With lumpectomy and radiation for small tumors, recurrence rates are low and survival is high. And while there may be some cosmetic alteration, usually women are very pleased with the appearance of the breast after lumpectomy and radiation. Studies with thousands of women, followed for many years, will be necessary to show that the results with in situ ablation are just as good before it can replace surgery as first line therapy.
It is too early to say which method will be the “state of the artâ€ÂÂ� for breast cancer ablation. It is most likely that different techniques may be necessary for different patients. Each of these techniques holds tremendous potential, and continued research is crucial. At this time, most of the on-going trials consist of in situ ablation followed by standard surgical resection. It is important for women to participate in these studies, for this information will hopefully allow women in the near future to have their breast cancers treated without surgical excision.

Michael S. Sabel, MD
Assistant Professor of Surgery
University of Michigan Comprehensive Cancer Center
Ann Arbor, MI 48109