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Cryoablation in early breast cancer.
Cryoablation: Nonsurgical treatment option in breast cancer

Breast cancer

Radiologic appearances of breast cancer.
Radioembolization in breast cancer liver metastases.
Intraarterial chemotherapy in breast cancer liver metastases.
Intraarterial chemotherapy in breast cancer.
Cryoablation is a viable option in breast cancer.
Cryoablation in breast cancer.
In cryoablation, the ablation area can be seen on ultrasound.
Complete removal of a benign breat mass bt BLES.
Complete removal of fibroadenoma using vacuum biopsy.
Image-guided breats biopsy.

For breast cancer patients, aggressive surgical operations has been the only option for many years. Today, thanks to the new technological developments, the vast majority of breast cancers can be treated with cryoablation. In this method, a cryo needle is inserted from the skin and placed into the center of the tumor under local anesthesia and ultrasound guidance. Then the tumor and the surrounding 1cm normal tissue is killed by freezing at -140 degrees. Recent studies have shown that the local recurrence rate is less than the surgical treatment in this method. Cryoablation is done through the needle hole, it takes 1 hour and the patient can go home immediately. There is no incision, no stitching, no deformation and no deterioration of breast aesthetics.


Breast cancer is the most common type of cancer in women; It was estimated that in one of every 8 women breast cancer would develop in a certain time. Breast cancer accounts for approximately 25% of all cancers in women. It is also seen in males but occurs about 100 times more common in females than males.


Breast cancer most often originates from milk channels called 'ducts' (ductal carcinomas) or units of milk glands called 'lobules' (lobular carcinoma). Approximately 10% of breast cancers show familial transition, in which BRCA1 and BRCA2 gene mutations can be detected. In addition, it has been shown that the incidence of breast cancer increases with obesity, sedentary life, hormone medications taken in menopause, alcohol consumption, early puberty and less breastfeeding. However, a significant proportion of patients may not have any risk factors.


Imaging methods in breast cancer

Breast cancer can be felt in the form of a mass during self-examination by the person or the doctor. Or, it can give other symptoms like breast thickening, stiffness, deformity, nipple retraction, bloody discharge. In such cases, ultrasound and mammography examinations are usually performed to determine if there is a suspicious mass in the breast. But sometimes, there is no complaint in the patient, and ultrasound and mammographies performed during routine controls may show a suspicious mass in the breast.


Ultrasound and mammography are the classical examination methods in the breast. Ultrasound is a cheap, practical and harmless (no radiation) method and it is the most commonly used examination in women under the age of 40 years. In mammography, the patient receives a small amount of radiation, but it is an indispensable diagnostic method especially for women over 40 years of age. Mammography shows cancer much clearly in breasts with a lot of fat. It cannot show cancer very well if the breast contains little fat and more fibroglandular tissue (dense breast)  which is more common in young women. In such dense breasts, one out of two cancers may be overlooked if only mammography is performed.

Ultrasound and mammography show different tumor structures better. For example, ultrasound shows the cystic masses in which the fluid is collected, and these masses are very well distinguished from solid ones.On the other hand, mammography demonstrates calcification areas better, which are hardly seen on ultrasound. Due to these complementary features, ultrasound and mammography are usually used together in the evaluation of breast masses. When mammography and ultrasound are used together, it is possible to determine 75-80% of all breast cancers.


Another method increasingly used recently in breast imaging is MRI (Magnetic resonance imaging). MRI does not use radiation, but it is more expensive and time-consuming. It is the most sensitive method (around 95%) to show the masses in the breast. Therefore, if a patient suspected of having a breast mass, has a normal MRI, the likelihood of breast cancer is largely ruled out. However, MRI also show benign masses more frequently than ultrasound and mammography and may cause confusion since it is not successful enough to differentiate cancer from benign masses (the specificity is low). Therefore, it is recommended MRI be used only supplementary to ultrasound and mammography in suspected cases and in high-risk patient groups. PET-CT is not used in routine breast examinations because it uses a higher radiation dose, but it is an extremely successful method for demonstrating the extention of breast cancer.


How is it diagnosed?

In the breast, benign masses are also frequently; about 80% of breast masses are benign while 20% prove to be cancer. In some of the breast masses (eg simple cysts, some fibroadenomas), the possibility of cancer can be practically ruled out by mammography and ultrasonography, and only routine follow-up is sufficient in such patients. In some patients however, the images are considered suspicious, and the degree of doubt is expressed by a classification called BIRADS. In BIRADS 1, 2 and 3 the mass is unlikely to be cancer and therefore, only regular follow-up is recommended. In BIRASDs 4 and 5, the possibility of cancer is high and biopsy is necessary.


Trucut (core) biopsy is the most commonly used biopsy method in breast. In trucut biopsy, a few millimeters wide and 1-2 cm long strips are taken from the suspected tissue and examined in pathology. In this way, the cancer is diagnosed, the subtypes of cancer are identified and receptor + genetic studies can be done, which can guide chemotherapy. The trucut biopsy is performed most frequently under ultrasonography guidance, if the mass is not seen on ultrasound, it can be performed on mammography and if it is not seen on mammography, it can be performed under the MRI guidance.














In some cases, it may be necessary to take a greater amount of tissue from the suspicious mass, or even remove the entire mass. In the past, this procedure could only be performed surgically, whereas today, it can be performed under local anesthesia through a hole of a few millimeters using vacuum biopsy or BLES methods. In the vacuum biopsy, a special needle placed in the breast apply suction on the mass and cut it into thick strips and remove them into a small container. In BLES (Breast Lesion Excision System) method, the sharp wires coming out from the edge of a special needle cut the surrounding tissue by heating with radiofrequency energy and grasp the mass as a whole and easily take it out. Both methods allow treatment of small benign masses, such as fibroadenoma, through a small incision without surgery. In some centers, BLES is also used for the percutaneous removal of  small breast cancers without surgery.


In breast biopsy, there are still some common mistakes: 1. Biopsy is performed by some surgeons by manual palpation without using ultrasound. In this method,  there is always a risk that biopsies will not be taken from the right place. 2. Thin needle use for biopsy instead of a trucut needle: Thin needle is used in thyroid nodules but is not suitable for breast and can cause many breast cancers to be missed. 3. Unnecessary use of surgical biopsy (excisional biopsy) after wire marking. On excisional biopsy, if the result is cancer, the patient will be operated for the second time, and this will not only be technically more difficult but also it will reduce the accuracy of the sentinel lymph biopsy for the evaluation of armpit lymph metastases. If the biopsy result is not cancer, the scar tissue may cause cancer-like appearances on ultrasound and mammography and makes follow-up difficult. In addition, the cost of surgery is higher than needle biopsy and it can disrupt breast aesthetics. For these reasons, the excisional biopsy should not be preferred except in mandatory cases.




In breast cancer, the stage of the disease should be determined in order to decide which treatment should be applied. As in other cancers, breast cancer is also divided into four stages. In stage 0, the cancer is limited to a milk canal or lobule (ductal carcinoma in situ, lobular carcinoma in situ). In stage 1, the tumor is less than 2 cm and there is no metastasis to the armpit lymph nodes. Surgical treatment or percutaneous cryoablation (freezing treatment) can be performed at this stage. In stage 2 and 3, the cancer may be larger in size, but it is still in the breast, but regional lymph nodes or even the chest wall may be involved. Surgical treatment is possible in these stages and chemotherapy and radiotherapy may be given. In stage 4, there are metastases in distant organs such as bone, lung, liver and surgery is useless. In this phase, the main treatment method is chemotherapy, and in cases where metastases are few or slow-growing, local treatment methods such as cryoablation may be added.


In breast cancer, there are some other factors that influence the clinical course and treatment. The most important of these are estrogen, progesterone and HER2 receptor levels in tumor cells. Estrogen, progesterone and HER2 bind to these receptors to provide rapid proliferation of tumor cells. Therefore, if these receptors can be blocked by certain drugs, the proliferation of cancer cells can be stopped or slowed down. Therefore, the presence of such receptors in breast cancer cells is considered a positive factor for the patient. The amount of these receptors can be determined from the pieces taken from breast biopsy and indicated in the biopsy reports to guide the treatment.


Classical treatments in breast cancer

As with many other cancers, classical treatment methods in breast cancer are surgery, radiotherapy and chemotherapy. In surgery, only the tumor itself (lampectomy), the region where the tumor is located, or the entire breast (mastectomy) may be removed. Nowadays, surgical methods that take the tumor and a portion of the breast are preferred, and mastectomy is considered the last option. During or after such operations, plastic surgery operations are also performed to protect breast aesthetics as much as possible. In breast-conserving surgical techniques, radiotherapy is also usually applied.


In breast cancer, methods such as manual examination, ultrasound + needle biopsy or sentinal (node) lymph node biopsy are performed to determine whether the tumor is spread to the armpit lymph nodes. If there is an intense involvement in these lymph nodes, the axillary lymph node dissection will remove the lymph nodes under the arm.


Most breast cancer patients require chemotherapy. Chemotherapy is given to reduce tumor burden in some patients and to facilitate surgical operation and is called "neoadjuvant chemotherapy". In some patients, it is given to reduce the likelihood of recurrence after surgery (adjuvant chemotherapy) and to improve survival. In estrogen, progesterone or HER2 receptor positive patients, drugs that block these receptors can be used besides the standart chemotherapy drugs.


Radiotherapy is used to kill tumor cells in breast and armpit that cannot be removed by surgery. Radiotherapy may not be necessary in some patients with mastectomy, but it is strongly recommended for patients undergoing breast conserving surgery.


Cryoablation and other interventional treatments in breast cancer

Breast cancer treatment has evolved over decades; once, the only treatment was radical mastectomy (removal of the breast and chest muscles) followed by mastectomy (removal of the breast only), quadrantectomy (removal of a portion of the breast) and finally lumpectomy (removal of the tumor only). Similarly, once, all patients undergoing breast surgery had also their armpit lymph nodes removed, followed by removal of nodes only if biopsy proves cancer, and finaly removal of lymph nodes only if the biopsy shows a "high tumor burden". In other words, surgical methods in breast cancer are becoming less and less aggressive and minimally invasive.
















As expected, the next step of this trend may be total abandonment of surgery and use of percutaneous ablation instead, for the treatment of breast cancer. In fact, during the last decade, many studies have shown that parcutaneous methods like cryoablation and even radiofrequency are very promising in the treatment of early stage breast cancer. In a multicentre study presented in 2018, 190 patients were treated with cryoablation and only 2 (1%) patients had local recurrence (relapse). These figures are even lower than the reported recurrence rates after surgery. Besides, cryoablation treatment has the following advantages over surgical operation.


1. Due to the natural pain relieving effect of cold, cryoablation is painless. Therefore, it can be applied using local anesthesia and can be done easily even in the doctor's office.

2. Since it is done through a needle hole at the skin, there is no incision, suture and scar, no deformation occurs in the breast and breast aesthetics will not deteriorate.

3. The ablation zone (iceball) is easily seen on ultrasound and it can be made sure that the entire tumor is frozen.

4. The patient can go home and return to normal life almost immediately following the operation.

The disadvantage of cryoablation is its relatively high cost. However, since there is no deterioration in breast aesthetics, the patient will not have to undergo additional cosmetic operations which may be more expensive.


For cryoablation of breast cancer, first the location of the tumor is determined on ultrasound, and then the area around the skin entrance and the tumor is numbed by local anesthesia. Subsequently, cryoprobes are placed in the tumor under ultrasound guidance. The ablation process lasts for an average of one hour. After the operation, the needles are taken out and the patient may be discharged after a few hours observation. If desired, the ablated area may be taken out by the vacuum biopsy device and is examined pathologically to make sure the tumor is completely dead. After cryoablation, radiotherapy may be given to the breast if necessary. Following  ablation, patients are examined for recurrence or metastasis at regular intervals by ultrasonography, MRI or PET-CT.


In some cases, intraarterial chemotherapy can be very useful in breast cancer. In this treatment, angiography is performed from the groin artery and the arteries feeding the breast tumor are identified. A tiny catheter is then inserted into these vessels and the chemotherapy drug is administered directly into the tumor. The chemotherapy given directly to the breast instead of whole body is more effective on the tumor and the systemic side effects may be reduced. This method can improve treatment response in locally advanced breast cancers and inflammatory breast cancer that do not respond well to standard therapy.






















New interventional treatments in breast cancer metastases

Interventional oncologic therapies are used extensively in breast cancer metastases. The standard treatment for breast cancer metastases is chemotherapy and currently, metastatic breast cancers can survive much longer than before as a result of improvements in chemotherapy drugs. During this long survival periods, some metastases in the body may not respond to chemotherapy, or previously extensive and multiple metastases may become more localized and few in number. In such cases, tumors may become suitable for local treatments like percutaneous ablation (e.g. RF, microwave, cryoablation).


Percutaneous ablation is most commonly used in the treatment of lung and liver metastases in breast cancer. "Heating" methods such as radiofrequency and microwave have been used successfully in both lung and liver. Cryoablation is a very good option in the breast itself and in the lung, in some cases it may also be preferred in the liver.

















In patients with breast cancer, if the metastases are only in the liver, or if they are predominantly in the liver, intraarterial chemotherapy, chemoembolization or radioembolization treatments can be applied. Intraarterial chemotherapy is based on the direct delivery of the chemotherapy drug from the feeding vessels into the tumors, and makes chemotherapy more effective. In liver metastases, intra-arterial chemotherapy can be performed with angiographies performed every 2-3 weeks. Or, a permanent  arterial port catheter is inserted from the groin, with its tip placed into the liver artery. In this way,  chemotherapy drugs can be given for a longer time at desired intervals.

Interventional oncology in cancer management

Prof Saim Yilmaz, MD

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