Dennis R. Holmes, M.D., F.A.C.S.
Breast Cancer Surgeon located in Santa Monica, CA & Los Angeles, CA
Dennis R. Holmes, M.D., F.A.C.S., with locations in Glendale and Los Angeles, California, is an expert in cryoablation and serves as principal investigator of the FROST Trial, a national clinical trial evaluating the use of cryoablation (tumor freezing) as an alternative to surgery for the treatment of early stage breast cancer.
Cryoablation Frequently Asked Questions
Frequently Asked Questions
- How is cryoablation performed?
- How do I prepare for the cryoablation procedure?
- What should I expect after the cryoablation procedure?
- What follow-up is needed after cryoablation?
- Can I receive cryoablation or participate in the FROST Trial if you live out of town?
- What are the imaging (e.g., mammogram or Ultrasound) requirements for successful cryoablation?
- Can I undergo cryoablation for DCIS?
- Does cryoablation eliminate the need for radiation or anti-cancer medications?
- Does cryoablation help the immune system fight breast cancer?
- How does cryoablation kill cancer cells?
- Should I have cryoablation performed by a breast surgeon or radiologists?
- Is it safe to undergo a needle biopsy of the cryoablation site after cryoablation?
1. How is cryoablation performed?
The cryoablation procedure is similar to having an ultrasound-guided needle biopsy of the breast. The procedure is performed in the office with the patient awake and comfortable. First, ultrasound of the breast is performed to identify the location of the cancer. Next, local anesthetic is injected into the skin and into to interior of the breast. A small (3mm) skin incision is made. Then a needle-like instrument called a cryoprobe is inserted through the skin incision and passed through the center of the breast cancer. The cryoablation system is then turned on and liquid nitrogen flows through the cryoprobe to freeze the cancer and a surrounding rim of normal tissue to a temperature of -185, an extremely cold cancer-killing temperatures. The freezing process takes approximately 30 minutes, and the entire procedure takes about 1 hour from start to finish.
2. How do I prepare for the cryoablation procedure?
Please download Dr. Holmes’s guide on “Final Preparations for Cryoablation”, which discusses how you should prepare for the cryoablation procedure.
3. What should I expect after the cryoablation procedure?
Expect Swelling of the Breast Right After the Procedure: Saline if usually injected under the skin to protect it from freezing. Depending on the amount of saline injection, you may have considerable swelling that increases the size of your breast. Don't worry. Your body will absorb the saline and your breast will return to near-normal size after a few of days.
Expect Bruising of the Breast After the Procedure: Bruising of the breast in normal after the procedure and usually develops in the first couple of days after the procedure and gradually disappears over a week. The bruising may sometimes extend to the flank below the breast.
Expect Drainage of Fluid from the Skin Puncture Wound. The small skin puncture wound through which the cryoablation probe is inserted will typically drain watery and bloody fluid for the first few hours after the procedure. The drainage should diminish and stop within 24-48 hours after the puncture wound seals. You will be given extra gauze pads to place inside your bra to absorb the drainage. Change the gauze as often as needed to keep your clothes dry.
Expect Some Persistent Swelling: The response to cryoablation usually caused swelling at the cryoablation site. This will make the tumor feel much larger than it did before the procedure. For example, cryoablation of a 2 cm tumor will produce a lump about the size of a large egg or small lemon which will gradually disappear over 2 years as your body absorbs to cryoablated tissue.
Expect Some Skin Redness: Redness of the skin is normal. It’s similar to a mild sunburn that will heal after a few days.
Notify Dr. Holmes is your experience any of the following:
--Shortness of breath
--Increasing pain that is not relieved by Tylenol
--Fever (Temperature ≧ 38.5C or 101F) or chills that develop after the procedure
--Bleeding from the wound that persists more than two hours and does not gradually diminish
--An open sore appears on the breast after the cryoablation procedure
4. What follow-up is needed after cryoablation?
The answer to this question depends on whether or not you are a participant in the FROST Trial.
FROST Trial participants are required to receive the following follow-up and treatments:
- Undergo a repeat needle biopsy of the cryoablated tumor six months after cryoablation to confirm that no living cancer remains
- Take an anti-estrogen pill daily for a minimum of 5 years
- Receive traditional 3 or 6 weeks of whole breast radiotherapy if younger than age 70
- Undergo a sentinel node biopsy if younger than age 70 and has a high risk tumor
- Undergo follow-up mammography, ultrasound, and breast MRI at regular intervals
OFF-PROTOCOL patients are not required to adhere to the follow-up biopsy and treatment plan. However, Dr. Holmes will work with you and your other healthcare providers to determined how best to customize the follow-up and treatment plan for you.
5. Can I receive cryoablation or participate in the FROST Trial if you live out of town?
Yes. You will need to come to Los Angeles for the cryoablation treatments, but arrangements can be made for you to receive your follow-up care in your home community. Dr. Holmes will work with your local healthcare providers to coordinate a follow-up/treatment plan for you.
6. What are the imaging (e.g., mammogram or Ultrasound) requirements for successful cryoablation?
There is a large body of evidence that cryoablation is capable of killing various types of cancer. However, the key requirement for successful cryoablation is a well-defined tumor that can be accurately targeted. Unfortunately, the complete extent of a breast cancer might not be detectable on mammography, ultrasound, MRI, or thermography. This is especially true for non-invasive breast cancer or ductal carcinoma in situ (DCIS), which is typically invisible unless it is associated with microcalcifications. DCIS co-exists with most invasive breast cancer, and may also extend a few millimeters or more beyond the main cancer mass. There may also be small, undetectable areas of invasive cancer outside the main tumor. Unlike surgery, which permits microscopic examination of the surgical margins to determine if cancer extends beyond the visible tumor, cryoablation does not permit microscopic examination of the tissue surrounding the visible tumor. Consequently, when cryoablation is performed for breast cancer, we intentionally freeze an area 1-2 cm beyond the visible tumor for the purpose of treating undetectable DCIS and/or invasive cancer in the immediate perimeter of the visible tumor.
7. Can I undergo cryoablation for DCIS?
Certain patients with DCIS (ductal carcinoma in situ, non-invasive breast cancer, or stage 0 breast cancer) may undergo cryoablation Off-protocol. Requirements include a small area of involvement (typically 2 cm or less) and DCIS that is visible by ultrasound, since cryoablation is usually performed under ultrasound guidance. When DCIS is not visible by ultrasound, Dr. Holmes can arrange for you to undergo insertion of an ultrasound-visible marker in the center of the area of DCIS (or next to your existing biopsy site marker), which could then be used as a target for the cryoablation procedure. Placement of the ultrasound-visible marker is usually performed under stereotactic or mammographic guidance using a procedure similar to your original stereotactic needle biopsy. In some cases, the marker placed at the time of the original needle biopsy is already ultrasound visible. When this is the case, placement of another ultrasound-visible marker is unnecessary. Dr. Holmes will need to review your mammogram, ultrasound, and MRIs to assess your eligibility for cryoablation, and to determine if placement of an ultrasound-visible marker is needed.
8. Does cryoablation eliminate the need for radiation or anti-cancer medications?
One of the major misconceptions with cryoablation is that it completely replaces the need for radiation or other treatments. With surgery, radiation is usually recommended to treat undetected residual disease in the surrounding breast, skin, or lymph nodes. In fact, the addition of radiation to surgery is generally associated with a 60% reduction in the risk of recurrence in the breast and lymph node area. Many patients treated with cryoablation would also benefit from radiation. Drug therapies like anti-estrogen therapy and chemotherapy have a role after surgery to treat cancer cells that had already escaped the breast. The same principle applies to cryoablation. Most patients treated with cryoablation would benefit from some form of anti-cancer drug therapy. Women certainly have the right to refuse radiation and medication therapy. However, the primary intent of cryoablation is to replace surgery, and other measures may be needed to minimize their risk of recurrence, especially for larger or more aggressive tumors.
9. Does cryoablation help the immune system fight breast cancer?
A main goal of cryoablation is to induce an immune response that might provide immunity to the cancer and prevent growth of residual or future disease in the breast, lymph nodes, or elsewhere. This is very much a goal, but the extent to which this occurs for the average breast cancer has yet to be fully established. Much of the evidence supporting the immune benefits of cryoablation has been demonstrated in animal studies performed under controlled conditions which might not represent what happens in living human. Although the vast majority of animal studies demonstrate stimulation of the immune system by cryoablation, some studies show immune suppression. Indeed, there numerous anecdotal reports of immune system stimulation in humans, resulting in regression of metastatic tumors following ablation of the primary tumors. However, there are also many examples in humans of where regression of distant metastatic sites did not occur. What is clear from the conflicting observations is that we still have a lot to learn about the natural immune response to cryoablation. We also have a lot to learn about how to amplify this immune response, perhaps using drugs or immune system stimulants, to achieve a more predictable and sustained anti-cancer immune response.
Until it is clearly proven that cryoablation provides immunity the breast cancer, it is best that patients remain open-minded about receiving radiotherapy and taking anti-cancer medications, especially if their cancers are larger or more aggressive.
10. How does cryoablation kill cancer cells?
Cryoablation kills cancers using 2 alternating freezing and thawing cycles which accomplish tumor kill via 5 mechanisms:
1. Osmotic injury
2. Mechnical injury
3. Vascular injury
4. Apoptosis or programmed cell death
5. Immunogenic injury
Osmotic injury. Rapid and sustained freezing of the tumor initially causes freezing of water and ice crystal formation in the extracellular space or the spaces between cells, which dehydrates the extracellular space. Dehydration of the extracellular space concentrates the electrolytes and proteins between the cells, which creates an osmotic gradient that forces water to flow from the interior of the cells (which have yet to freeze) to the extracellular space to restore the water balance outside the cells. Forced withdrawal of water from within the cells causes the cells to shrink and crinkle, creating cracks in the cell membrane or cell wall. During the subsequent thaw cycle, ice crystals in the extracellular space thaw and dilute the electrolytes and proteins and between the cells. This forces the excess extracellular water to flow back into the cells that are now relatively dehydrated compared to the extracellular space. This flow of water back into the cells causes them to swell and then rupture because the cell walls has been damaged from prior shrinkage. As it turns out, the killing properties of a long thaw cycle seems to be as important as the killing properties of a long, cold freeze cycle.
Mechanical injury. Although ice crystal information in one of the earliest changes during the freeze cycle, colder and sustained freezing cause formation of large ice crystals inside of the cells, with directly damages intracellular structures, like the DNA-containing nuclei, energy-creating mitochondria, and intracellular cytoskeletons that help to maintain cell shape. With each subsequent cycle of freezing, the damaging tissue conducts the freezing with increasing efficiency, which progressively increases the diameter of the cryoablation zone.
Vascular injury. Cancer cells rely on blood vessels to carry deliver oxygen and nutrients and eliminate waste. During cryoablation, small and medium size vessels within and surrounding the tumor are killed in very much that same way that cancer cells are killed. In addition, damage to the lining of the blood vessels cause clot formation in the vessels feeding the tumor, which further deprives the cancer cells of oxygen and nutrition, a combination of events that contributes to tumor kill. In addition, restoration of blood flow around the cryoablation zone after thawing releases chemicals called “free radicals” that reinjured the vessel lining which causes further clot formation. (It is recommended that you avoid taking aspirin within 10 days before or after cryoablation since Aspirin inhibit platelets that are essential for clot formation.)
Apoptosis (pronounced “a-po-toe-sis”) or programmed cell death. The tumor next to the cryoprobe in the center of the cryoablation zone reaches the coldest temperature, as low as -180 C. However, the temperature near the outer portions of the cryoablation zone and farther from the cryoprobe do not reach such a low, direct-tumor killing temperature. Despite this, “warmer” sub-lethal temperatures in the range of 6 degrees C to -10 C are capable of activating enzymes within the cancer cells that destroy the intracellular proteins and DNA. This phenomenon, called apoptosis or programmed cell death, essentially causes the cancer cells to commit suicide. (Programmed cell death from cold temperature has been exploited as a weight loss method by plastic surgeons, who now employ a new technology called CoolSculpting, that uses cold temperatures in the range of 4 degrees C to induce apoptosis of fat cells.)
Immunogenic injury. Although the strength of a generalized, systemic immune response remains to be fully understood, experimental studies show that abnormal cancer cell proteins are capable of inducing an immune response at the tumor site in two key ways: 1) uptake of abnormal tumor proteins by immune cells (granulocytes, monocytes, and macrophages) that stimulate formation of antibodies (and possibility immunity) that bind to cancer cells and target them for attack by T-cells, and 2) uptake of abnormal tumor proteins by antigenic presenting cells like dendritic cells and macrophages that directly stimulate T-cells to attack the cancer as foreign cells. A third and increasing important immunogenic mechanism is that killing of cancer cells prevents them from producing “checkpoint proteins” that bind to nearby T-cells and function as a brake on the immune system that prevents it from attacking the tumor. There is now a whole new field of immunotherapy focused of developing immune checkpoint protein inhibitor drugs to turn off the break that some cancers place on the immune system.
11. Should I have cryoablation performed by a breast surgeon or radiologists?
An important consideration is whether or not, if given the option, you would seek cryoablation by a radiologist who would perform the procedure as a stand along treatment, or by a breast surgeon who not only perform the cryoablation procedure, but also commit to providing ongoing follow-up care, coordination of care with your local healthcare providers, and supervision or facilitation of ongoing imaging follow-up. These latter points are very important, because many local doctors and radiologists are unfamiliar with cryoablation or the imaging appearance of cryoablated breasts, and are therefore reluctant to advise patients regarding their care. As a result, some cryoablation patients are left to figure these things out on their own.
Cryoablation of breast cancer is more than just a technical procedure. The cryoablation procedure itself might be “the end” of the cancer in the breast, but it’s only the beginning of your cancer survivorship. Breast surgeons are accustomed to providing long-term follow-up, treatment counseling, recurrence risk-reduction counseling, care coordination, and post-treatment imaging evaluation for breast cancer survivors. If your only option for cryoablation is a radiologist, make sure she/he is collaborating with another oncologist who is committed to helping you navigate the other aspects of your long-term care and survivorship, including follow-up breast examination, breast imaging, and possibly other cancer treatments.
12. Is it safe to undergo a needle biopsy of the cryoablation site after cryoablation?
There is a myth that performing a needle biopsy of the cryoablation site weeks or months after cryoablation will interfere with the immune response. There is absolutely no objective evidence supporting this view. Many clinical trials participants have safely undergone needle biopsy procedures after cryoablation with absolutely no harmful events. Mammogram, ultrasound, MRI and thermography are imperfect and not 100% reliable at eliminating the possibility of residual disease at the cryoablation site. Furthermore, natural post-cryoablation inflammation in the breast might sometimes look like a cancer recurrence. Consequently, needle biopsy might be recommended by your doctor to confirm that no living breast cancer remains in the treated area. Indeed, a 6-month post-cryoablation needle biopsy is required by some clinical trials, including the FROST Trial. You may now feel reassured that a subsequent needle biopsy will not interfere with your recovery from cryoablation.