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Answers

 

1. WHAT ARE THE POSSIBLE BENEFITS OF UNDERGOING THIS PROCEDURE?  

 

The main benefit of undergoing cryoablation is that your cancer might be adequately treated without the need for breast surgery. Cryoablation avoids potentially negative cosmetic effects of breast cancer surgery by eliminating the need for tissue removal, a large breast incision, or breast reconstruction. Cryoablation is performed under local anesthesia which allows you to avoid general anesthesia.  The complications of cryoablation are less than surgery. Patients are able to return to usual activities within a matter of a days.

 

2. WHAT ARE THE POSSIBLE RISKS AND DISCOMFORTS?

 

Expect mild pain:  Injection of local anesthesia causes temporary pain followed by numbness. The cryoablation procedure itself might also cause temporary pain near the back of the breast, followed immediately by numbness since the freezing process is pain-relieving. Local anesthetic injected during the procedure usually wears off after 4-6 hours. Acetomenophen (e.g., Tylenol) is usually sufficient to control breast pain after the procedure. Only rarely do patients need narcotic pain medications after cryoablation. 

 

Expect Swelling of the Breast Right After the Procedure: Saline may be injected under the skin to protect it from freezing. Depending on the amount of saline injected, you may have considerable swelling that temporarily increases the size of your breast. 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 is normal after cryoablation and usually develops in the first few days after the procedure, usually peaking in 3-5 days. Bruising gradually disappears over 10 days.  The bruising may sometimes spread to the flank or upper abdomen.  

 

Expect Drainage of Fluid from the Skin Puncture Wound: The small skin puncture wound through which the cryoablation probe is inserted commonly drains watery and bloody fluid after the procedure during the first 12 hours.  You may be given extra gauze pads to place inside your bra to absorb the fluid. Change the gauze as often as needed to keep your clothes dry.  If the drainage washes off the cloth tape (Steri-strip) that is applied to the incision at the end of the procedure, simply apply antibiotic ointment to the incision daily until the incision heals.

 

Expect Some Persistent Swelling: The body’s initial response to any injury is swelling at the site of injury. The same is true for cryoablation. Swelling will make the tumor area feel much larger than it did before the procedure.  For example, cryoablation of a 2 cm breast cancer will produce a lump about the size of a large egg or small lemon, which gradually disappears over several years as your body absorbs the cryoablated tissue.  You should NOT expected the cryoablated area to become sunken as it heals. The original shape of the breast is usually maintained.

 

Expect Some Skin Redness: Redness of the skin is normal.  It is similar to a mild sunburn that heals after a few days. Effort will be made to protect the skin from a cold/freeze injury.  However, in some instances, a mild frost-bite injury will cause blistering, loss of skin pigmentation at the frost-bite site, and/or skin ulceration. When blistering or ulceration occurs, the wound typically heals closed with topical wound care (antibiotic ointment and bandages). Eventually, the skin color will gradually return to normal or near-normal color. Infection after cryoablation is rare, but possible, and will need to be treated appropriately.

 

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3. IS THERE A RISK OF RECURRENCE IN THE BREAST AFTER CRYOABLATION?

 

The success of cryoablation depends on the ability of the cancer to be completely and accurately targeted.  If mammograms, ultrasound, or MRI underestimates the size and location of your cancer, then parts of the cancer may remain untreated or undertreated and therefore not killed by cryoablation.  In some cases, the doctor will arrange to have an ultrasound-visible marker inserted into the center of the cancerous area to make the area a clearer target for ultrasound-guided cryoablation, which is the preferred cryoablation approach.

 

To increase the chance of complete cancer kill, Dr. Holmes will aim to cryoablate the cancerous area as well as a rim of normal tissue surrounding the cancerous area in case the cancer is actually larger than it appears on mammogram, ultrasound, or MRI.  However, complete cancer kill cannot be guaranteed by cryoablation since invisible parts of the cancer may extend beyond the cryoablation area.  If the cancerous area is not completely killed, the untreated areas might grow and spread beyond the breast.  To reduce the risk of the cancer spreading, it is recommended that the treated breast be monitored regularly for signs of remaining or recurring cancer so that it can be detected, biopsied and treated appropriately. Similar to patients treated with surgery, appropriate anti-cancer medications and radiation therapy after cryoablation can also reduce the risk of recurrence in the breast and beyond.

 

4. DOES CRYOABLATION ELIMINATE THE NEED FOR ANTI-CANCER MEDICATION AND/OR RADIATION?

 

Cryoablation is intended to eliminate the need for breast surgery but it does not eliminate the need for standard treatments that are essential components of comprehensive cancer care that, when combined with cryoablation, aim to reduce the risk of cancer recurrence to a low level. Depending on your age and cancer characteristics, you might be advised to receive treatments like radiation, anti-estrogen (endocrine) therapy, chemotherapy, lymph node surgery, and/or anti-HER2/neu immunotherapy.  Anti-cancer medication are given to treat cancer cells that may have already metastasized to distant parts of the body even if there is no detectable cancer cells remaining within the body. Radiation is usually given after lumpectomy to treat invisible tumor cells that might be present outside the tumor. Even patients treated with lumpectomy or mastectomy might be advised to receive one or more of these treatments to reduce the risk of cancer recurrence in the breast area and/or elsewhere within the body. Dr. Holmes will let you know which of these treatments are appropriate for your cancer and discuss the benefits and risks of each.  You will also be advised to consult with other cancer specialists that play a role in administering these treatments.  

 

It’s important to understand that no combination of treatments can completely eliminate the risk of breast cancer recurrence, but radiation, anti-estrogen (endocrine) therapy, chemotherapy, anti-HER2/neu immunotherapy, and/or lymph node surgery have been clearly shown to dramatically reduce the risk of breast cancer recurrence within the breast and elsewhere within the body, especially for higher-risk cancers.  Depending on your cancer characteristics and estimated risk of recurrence, you might be advised to consider certain other treatments (e.g., anti-estrogen therapy). At the end of the day, it is up to you to follow through with additional recommended treatments after cryoablation to minimize your risk of breast cancer recurrence within the breast and elsewhere within the body.   

 

Cryoablation of breast cancer is still considered an experimental treatment by many doctors.  As a result, some consulting doctors may not feel comfortable treating you with radiation or other standard treatments.  If needed, Dr. Holmes might be able to help you identify consulting doctors to assist with your cancer treatment and follow-up. It might also be necessary to seek these treatments from a consulting doctor outside of your home community.

 

 

5. SHOULD YOU HAVE CRYOABLATION PERFORMED BY A BREAST SURGEON OR RADIOLOGIST?

 

An important consideration for women considering cryoablation is whether or not, if given the option, you should choose to have cryoablation performed by a breast surgeon or radiologist. The bottom line is that treating a patient with breast cancer is more than just 1 hour radiology procedure. Although radiologists possess the technical skills to perform cryoablation, the advantage of seeking cryoablation from a breast surgeon is that breast surgeons are better suited to helping women weigh the pros and cons of cryoablation compared to other treatments, discuss the alternative, make referrals, perform a lymph node biopsy, if needed, and order follow-up imaging and biopsies, if needed. Breast surgeons are generally more committed to providing ongoing follow-up care, coordination of care with your local healthcare providers, and providing or facilitating ongoing follow-up. 

 

 

6. WHAT TRADITIONAL CANCER TREATMENTS SHOULD I CONSIDER?

 

Breast Surgery: Lumpectomy or mastectomy surgery are the current standard treatments for breast cancer.  Unlike cryoablation, lumpectomy and mastectomy permit complete removal of the cancerous area and assessment of the surgical margins to confirm that the area has been removed completely.  Additional breast surgery might be recommended if cancer removal is judged to be incomplete. 

 

Preliminary results of several cryoablation studies indicate that cryoablation may be an effective alternative to surgery for estrogen or progesterone-sensitive breast cancers measuring 2 cm or smaller, and without evidence of lymph node spread. There are no conclusive studies showing the effectiveness of cryoablation in the treatment of breast cancers greater than 2 cm, breast cancers with lymph node involvement, breast cancers that have previously been treated with chemotherapy or anti-estrogen therapy, recurrent breast cancers, multiple cancers in the same breast, non-hormone dependent breast cancer (like triple negative breast cancer), non-invasive breast cancer (ductal carcinoma in situ or DCIS), or invasive lobular breast cancers.  However, on a case-by-case basis, Dr. Holmes might agree to perform cryoablation on larger or higher risk tumors if you are unwilling to undergo surgery. 

 

To make an informed decision about cryoablation, your doctor should give you an estimate of your risk of recurrence after lumpectomy, mastectomy, or cryoablation, as best as they can be determined.   

 

Lymph Node Surgery: Cryoablation of the cancer within the breast is unlikely to slow or prevent growth of cancer cells that have already spread to the nearby underarm lymph nodes.  Therefore, sentinel node biopsy (removal of just a few normal appearing nodes) and axillary lymph node dissection (removal of cancerous lymph nodes) are the standard surgical procedures performed to detect and/or remove cancer-containing lymph nodes in the nearby underarm area.  One exception to this rule is that most women age 70 and older with estrogen and/or progesterone-sensitive breast cancers can avoid lymph node surgery if they are willing to take anti-estrogen therapy. Another exception is that women of any age with pure ductal carcinoma in situ (DCIS) do not require lymph node surgery. However, all other women should discuss the pros and cons of  lymph node surgery. Some low risk tumors might night require lymph node surgery.

 

Information obtained from lymph node surgery can help guide your overall cancer treatment.  Lymph node surgery is performed in the hospital under general anesthesia or local anesthesia with sedation.  Dr. Holmes will discuss with you if cryoablation is needed and the appropriate timing of the lymph node procedure, either before or after the cryoablation procedure.

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Management of the lymph node depends, in part, on the condition of the lymph nodes. For women with POSITIVE lymph nodes, Dr. Holmes recommends lymph node surgery as the preferred procedure even if cryoablation is performed on the breast. This is especially true for women with multiple positive lymph nodes or positive nodes close to large underarm blood vessel, where cryoablation might be less safe or less effective. However, cryoablation may be performed in women with only one or two positive nodes if the lymph nodes are located in a safe area.

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Women with NEGATIVE lymph nodes can usually be managed without lymph node surgery if the patient is willing to 

undergo regular imaging studies (e.g., ultrasound)  to screen for evidence of lymph node recurrence so that the problem may be managed quickly. Failure to undergo recommended lymph node surgery can lead to uncontrolled cancer growth to more lymph nodes or to other parts of the body.  The one key exception to this rule is that patients with Triple Negative Breast Cancer and HER2/neu positive breast cancer are advised by Dr. Holmes to undergo sentinel node biopsy even if the lymph nodes appear normal because the status of the lymph nodes in these women have a strong influence on overall treatment recommendations.  Although patients have the right to refuse lymph node surgery in these circumstance, you will be advised to strongly consider it.

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If you agree to have lymph node surgery performed, Dr. Holmes will schedule the lymph node surgery 1-2 days before or 1-2 days after cryoablation depending on the extent of cancer, the location of your tumor, and based on other logistical considerations.

                                                                                         

Radiation: In general, radiation reduces the relative risk of cancer recurrence within the breast by 60% beyond what is usually achieved by surgery or cryoablation or cryoablation alone.  The actual magnitude of benefit of radiation depends on your personal estimated risk of recurrence.  To make an informed decision about radiation, Dr. Holmes will give you an estimate of your risk of recurrence both with and without radiation, as best as it can be determined. 

 

For example, if your estimated 10-year risk of recurrence with cryoablation alone is 50%, radiation will generally reduce your risk to 20%, which a 60% lower relative-risk of recurrence.  If your estimated risk of recurrence with cryoablation alone is only 5%, then radiation will further reduce the risk to 1.5%.  Based on this risk estimate, you can decide if radiation is right for you. 

 

For women with ductal carcinoma in situ, Dr. Holmes will recommend a commercial test to estimate your personal risk of recurrence. In most cases, the test is covered by insurance.
 

 

Anti-estrogen (endocrine) therapy: In general, anti-estrogen (endocrine) therapy reduces the risk of recurrence of estrogen and/or progesterone receptor positive cancers by 50% on top of what is usually achieved by other treatments (e.g., surgery, cryoablation, and radiation).  Anti-estrogen (endocrine) therapy also reduces the risk of cancer recurrence in the lymph nodes, the opposite breast and other parts of the body.  The actual benefit of anti-estrogen therapy to you depends on your personal estimated risk of recurrence, which is determined by your personal tumor characteristics. For example, if your estimated 10-year risk of recurrence is 12%, radiation will generally reduce your risk to 6%, which a 50% lower relative-risk of recurrence. In some cases, Dr. Holmes will recommend a commercial test to estimate your personal risk of recurrence.  In most cases, the test is covered by insurance.

 

Chemotherapy: Chemotherapy has the potential to reduce the risk of cancer recurrence within the overall body, lymph nodes and breast on top of that which is achieved by surgery, cryoablation, radiation, and anti-estrogen therapy. The actual benefit of chemotherapy depends on your personal tumor characteristics. In most cases, Dr. Holmes or your medical oncologist will recommend a commercial test to estimate your personal 5- or 10-year risk of cancer recurrence.  In most cases, the test is covered by insurance.  

 

Anti-HER2 immunotherapy: In general, anti-HER2 immunotherapy medications like Herceptin and Perjeta reduce the risk of cancer recurrence and are highly effective against breast cancers that make excessive HER2 proteins.  The actual benefit of anti-HER2 immunotherapy to you depends on your personal estimated risk of recurrence. Anti-HER2 immunotherapy is most effective when combined with chemotherapy. Patients who refuse chemotherapy may sometimes be offered anti-HER2 immunotherapy without chemotherapy. 

 

Immunotherapy:  There is a common belief that cryoablation stimulates the immune system to build natural immunity against the cancer. This phenomenon has been demonstrated in animal studies but remains unproven in humans. Therefore, until we understand better the immune effects in humans, it is recommended that you follow through with standard cancers treatments to reduce the risk of recurrence.

Because immunotherapy injections is offered by some doctors, you should understand the current state of affairs about the use of immunotherapy injections with Cryoablation.... Whereas immunotherapy MAY be injected at the time of Cryoablation, the evidence supporting its use or benefits in humans is POOR. The only published clinical trials involved patients with triple negative invasive breast cancer. In the most relevant triple negative breast cancer study, all patients received a dose of Opdivo (nivolumab) immunotherapy EVERY 2 WEEKS up to 42 doses. The survival improvement from this nearly 1 year course of therapy was only 2 months. Moreover, one-third of the patients experienced MODERATE to SEVERE side effects of various types. Furthermore, triple negative (and HER2+) are the types of breast cancer, if any, considered, in theory, most likely to respond to immunotherapy--which means that other types like ER+ or HER2 negative breast cancer would be expected to show even less, if any, survival benefit despite a nearly 1-year course of Opdivo.

The TAKE HOME MESSAGE: There is no evidence in humans that a SINGLE dose of immunotherapy of any type would have any cancer control or survival benefits. There is no evidence in humans that Cryoablation+immunotherapy has any survival benefit for hormone receptor positive breast cancer (like ILC or invasive lobular breast cancer). There is no evidence in humans that an intratumoral injection is the best way to administer immunotherapy with Cryoablation. For these reasons (among others), most of us who perform Cryoablation believe that Optivo and similar immunotherapy drugs should be administered only in the context of formal IRB-approved clinical trials that will help up understand the true benefits and risks of the immunotherapy, the correct mode of administering the immunotherapy, the types of breast cancer most suitable for immunotherapy, and the proper dosage/frequency to achieve a cancer control or survival benefit, if achievable. I have in the past and continue to encourage physicians who administer immunotherapy injections with Cryoablation to conduct such formal, IRB-approved clinical trials in humans. I'd be happy to join them or support their efforts in this research just as I have supported the triple negative breast cancer clinical trials mentioned above. OUTSIDE of an immunotherapy clinical trial, buyer beware. Although animal (mouse) experiments show promise for cryoablation+immunotherapy, these studies are conducted in idealized experimental that in the vast majority of cases are not translatable to humans. Thus, doctors offering immunotherapy injections to WOMEN outside of a human clinical trial should be absolutely clear that there is no evidence that it works reliably in humans, and that it could have unrecognized harms. With this information, you are free to make a decision regarding your care. That's what INFORMED consent is all about.

 

 

Other strategies:  In addition to the standard treatments discussed above, your doctor should discuss with you lifestyle modifications and other strategies that might further reduce your risk of cancer recurrence.  Some women choose to avoid standard treatments and instead pursue complimentary or alternative therapy. Please understand that the effectiveness of many complimentary or alternative treatments remains unproven.

 

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Clinical trials: Dr.Holmes is a strong supporter of clinical trial participation. However after undergoing cryoablation, 

you might be disqualified from participating in clinical trials that require participants to undergo surgery.  If you are considering participation in a clinical trial, make sure that cryoablation does not disqualify you from participating in the clinical trial. 

 

7. HOW IS THE BREAST MONITORED AFTER CRYOABLATION?

 

To monitor the healing of your breast and to look for signs of cancer recurrence, it is recommended that you receive follow-up imaging studies (e.g., mammograms, ultrasound and breast MRI) at regular intervals after cryoablation.  Your cryoablation doctor should help you figure out the right screening regimen after cryoablation based on your age, cancer characteristics, and estimated risk of recurrence. In addition, you should consider undergoing a needle biopsy of the cancerous area sometime after cryoablation to confirm that the cancer has been completely killed by cryoablation.  Failure to perform one or more of the breast imaging and/or needle biopsy procedures could lead to a delay in the detection of a cancer recurrence.  

 

Since cryoablation is a relatively new procedure for treating breast cancer, most radiologists do not have extensive experience interpreting mammograms, ultrasounds, and contrast-MRI of patients treated with cryoablation. This lack of experience could contribute to a delay in detection of cancer recurrences or result in additional and perhaps unnecessary biopsies being recommended to evaluate unclear imaging findings.  Despite these challenges, it is recommended that you undergo regular breast imaging with mammograms, ultrasound, and/ or MRI to reduce the chance of missing a cancer recurrence.  

 

It should also be noted that some radiologists are uncomfortable interpreting mammograms, ultrasound, and contrast-MRI images after cryoablation.  As a result, it might be necessary for you to shop around for a radiologist willing to interpret your imaging studies.  Dr. Holmes can also help you locate a radiologist experienced with interpreting post-cryoablation imaging studies.

 

 

8. WHEN IS SURGERY REQUIRED AFTER CRYOABLATION?
 

Lymph node surgery is commonly recommended before or after cryoablation to check for cancer in the lymph nodes or to remove cancerous lymph nodes.  

 

In addition, your doctor will recommend surgery after cryoablation if any of the following occur:
 

-- A needle biopsy of a suspicious area shows that your cancer was not completely killed or has recurred.  However, in most instances, cryoablation can be repeated on the recurrence.

--Your cryoablation procedure cannot be completed. Reasons why the procedure might not be completed include technical difficulties or your anxiety or discomfort.

--You develop a breast cancer in a different area of the same breast. However, in most instances, cryoablation can be repeated on the recurrence.

--Needle biopsy of a suspicious lymph node shows that cancer has developed or recurred in the lymph nodes.

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9. WHAT ARE ADDITIONAL SIDE EFFECTS AND RISKS OF CRYOABLATION?
 

In most cases, the side effects of cryoablation are much less severe than the side effects of surgery.  Many side effects go away soon after you recover from cryoablation.  In some cases, side effects can be serious, long-lasting, or may never go away.

 

Common Risks:

--Temporary pain with injection of anesthetic agent (e.g., Lidocaine, Marcaine)

--Brief period of pain during the cryoablation procedure

--Mild bleeding or drainage of bloody fluid from cryoprobe insertion site

--Swelling of the breast after cryoablation

--Bruising of the breast after cryoablation

--Tenderness of the breast at the cryoablation site

--Shoulder stiffness lasting a short time after cryoablation

--Skin blisters caused by bandages

--Skin redness caused by freezing

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Uncommon Risks (seen in less than 5% of procedures):

--Freezing and damage to skin

--Wound infection

--Significant bleeding from cryoprobe insertion site requiring placement of a suture

--Allergic reaction to anesthetic agent (e.g., Lidocaine, Marcaine)

--Skin blister or ulcer caused by freezing

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 Rare Risk (seen in less than 1% of procedures):

--Puncture of lung (rare). Dr. Holmes has never had this complication.

 

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10. WHAT OTHER OPTIONS ARE THERE?

 

If you choose not to undergo cryoablation:

 

---You may choose to receive standard surgery (lumpectomy or mastectomy and lymph node surgery), radiotherapy, and drug therapy in some combination.

--You may choose to seek alternative therapy for your breast cancer.

--You may choose to have no treatment for your breast cancer.

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11. CAN POSITIVE LYMPH NODES BE CRYOABLATED?

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The answer to the question is "it depends."  Lymph nodes are a common site of cancer metastasis. If it is possible to cryoablate a breast tumor, it's reasonable to assume that lymph nodes may also be cryoablate.  However, the safety and effectiveness of lymph node cryoablation depends on the lymph node's location and the number of lymph nodes believed to be involved.   Why is lymph node location important?  Unlike the breast, the underarm area is a VERY busy place. It contains lots of lymph nodes mixed among criss-crossing blood vessels, lymphatic vessels, and nerves coming to and from the breast and arm.  Any of those structures are potentially at risk of injury when a lymph node is cryoablated.  The SAFEST location for lymph node cryoablation is a node that is located close to the breast, typically below the hair-bearing area of the axilla, where there are fewer criss-crossing structures.  Fortunately, this is where most positive nodes are found. On the other hand, cryoablation of lymph nodes in the upper axilla can cause collateral damage (freezing) to nearby blood vessels, lymphatic vessel, and nerves, which can increase the risk of lymphedema and chronic nerve pain. Furthermore, the high blood flow of warm blood in large blood vessels in the upper axilla can interfere with effective freezing. As a result, surgical removal of high-lying nodes MIGHT actually be a safer and more effective solution, especially when combined with axillary reverse mapping and other surgical techniques to identify and spare nearby lymphatic structure. (This is yet another reason why having cryoablation performed by a surgeon is preferred---he or she can offer the most effective and safest solution--ablation +/- surgery for your unique problem. The number of suspicious or positive lymph nodes also matters.  Ablation of 1 or 2 adjacent nodes can usually be perform safely.  However, ablation of a larger number of nodes will likely create a large freeze zone that will unintentionally injure adjacent normal nodes as well as other nearby structures.