Innovations in Breast Cancer Treatment!

The most common type of cancer in women, breast cancer d. Risk factors leading to breast cancer in women include hormonal factors such as having breast cancer in the vicinity of the first degree in the family and seeing menstruation at an early age, cutting off from the body at an advanced age (late menopause), excessive weight gain and using hormone uncontrolled in menopause. At first grade, mother, daughter and sister should come to mind as a relative. About 10-15% of genetic breast cancers are encountered. BRCA1 and BRCA2 genes are genes responsible for hereditary breast / ovarian cancer syndrome. Hereditary or familial breast cancer is characterized by the presence of breast and / or ovarian cancers in a large number of females within the family, the emergence of disease in the 20s and 30s, and the presence of bilateral breast cancer patients. For women who have a very high genetic risk, following this definition, it may be advisable to take protective ovaries after completing their births and to evacuate the inside of two protective nipples (protective mastectomy for the skin and nipple).

Early recognition of breast cancer increases chances of healing. Screening for breast cancer begins at age 40 for mammograms. For those who have regular mammography, this method can be used to diagnose cancer before the mammary gland appears. In high-risk patients, imaging with mammography and magnetic resonance imaging (MRI) is recommended. More recently, "tomosynthesis" has used imaging. In this method, thin sections such as tomography are taken. According to the results of the clinical study, the visualization of the lesion increases, border evaluation becomes easier, recall and close follow-up rate decrease, and lesion localization is better. This imaging method, which is used in several centers in Istanbul, increases the early diagnosis possibilities.

When mammograms are taken, sometimes the focus can be seen with tiny calcification called "microcalcification". These foci can be a sign of an early breast cancer and biopsies can be taken from these foci for imaging. Biopsies are usually taken with ultrasonography, but with advanced MR technology, biopsies can only be obtained from MR lesions.

Occasionally, these small foci, which are not recognized by the hand specimen, are surgically removed by marking them with a wire or radioactive substance. If marked with a radioactive substance within a few hours when the wire is marked, surgery should be performed within a day. According to the biopsy result, the lesions observed to be cancer are being widened, while the sublingual lymph nodes are also checked.

Nowadays, apart from some special cases, only a limited part of the mammary is removed, and under the armpit, there is no attempt as wide as the old one. For this purpose, a method called "sentinel lymph node biopsy" is used. In this method, it is essential to inject a special blue dye or a radioactive substance into the cancerous region of the breast, to spread this dye or radioactive substance under the armpit and to remove the stained lymph nodes (sentinel lymph node). If these lymph glands are not found in the cancer cell, there is no need for additional interventions. Thus, an unwanted problem such as swelling in the cord is not allowed. However, in cases where cancer cells pass into the lymph nodes, a second operation requires the removal of all of these lymph nodes, ie axillar krajing.

Sometimes the tumor can be quite large, or it can lead to nipple retraction, shape and color change in the breast skin, inflammation. In this case, chemotherapy is applied before the surgery, the tumor is minimized and the skin changes are corrected and then given to the surgeon. Over the past year, we have seen very successful treatment results in this patient group. In particular, it has been shown that patients treated with high-risk HER2 oncogen expression can undergo complete tumor recurrence with targeted therapies (such as trastuzumab, pertuzumab, lapatinib). Considering the age of the patient and other diseases present in the hormone sensitive tumors, this tumor reduction can be performed with hormone therapy.

However, if the disease has jumped to other organs, in other words metastasized, it is suggested that systemic treatment and, if necessary, radiotherapy should be discontinued without surgery. That is, the type of treatment is determined by taking into account the regional prevalence of the disease (breast and axillary) and the extent of spread to other organs. We define this prevalence as staging of the disease.

It is accepted that micrometastases are present even at the time of diagnosis that breast cancer is a systemic disease.
For this reason, in the last 30 years, both disease free survival and overall survival rates have been significantly increased by adjuvant chemotherapy and hormonotherapy aimed at eliminating microscopic metastases in addition to surgical treatment of early stage breast cancer. Recently, biological therapy has been added to these. In planning an appropriate adjuvant treatment, some factors are noted. The age of the patient, the diameter of the tumor, the number of metastatic lymph nodes under the arm, the expression of hormone receptors (estrogen receptor, briefly ER and progesterone receptor, briefly PR), other diseases present in the patient and HER2 / neu gene expression are among the parameters determining the course and treatment of the disease . Anti-estrogen therapy is not used in cases of breast cancer that does not carry hormone receptor, and in the case of breast cancer without HER2 / neu gene expression, the benefit of biological treatment called trastuzumab is not expected. More recently, the risk profile of the disease has been elaborated more precisely by looking at the gene profile of the tumor. With this method, it is tried to determine the groups that need preventive treatment more clearly. This method, which is very costly, provides an important support to physicians to guide the "uncertainty about adjuvant treatment".

In the choice of treatment, the biologic features of the tumor are very important. Three types of breast cancer are defined by considering the molecular and pathological features; HER2 / neu disease, hormone receptors (ER, PR) and HER2 / neu gene expression (basaloid) disease and ER positive disease. Biological treatment planning is being done according to the targets of adjuvant treatment. For example, ER positive disease hormone therapy is recommended, while ER negative patients do not benefit from this treatment. While trastuzumab is highly effective in HER2 positive disease, it does not benefit HER2 negative patients. Trastuzumab is a monoclonal antibody against HER-2 / neu oncogenes that is present in 20-25% of breast cancers. It is used intravenously and proven to be beneficial both in preventive treatment and widespread disease. In those patients who have gained resistance, a newer drug called lapatinib, which is used orally, has been used. The mechanism of action of lapatinib is different from trastuzumab and has been shown to play a role in the breakdown of resistance to hormone treatment.

The first conservative (adjuvant) chemotherapy trials in breast cancer began in the 1970s in Europe with the work of Bonadonna and his colleagues. In this study, it has been shown that both patients without chemotherapy and patients with chemotherapy have significantly improved overall survival. Afterwards, in an American study by Fisher and colleagues, it is clear that adjuvant chemotherapy extends survival. With adjuvant chemotherapy, patients with surgically treated breast cancer are at a reduced risk of recurrence without age, lymph node status, hormone receptor status, or menopausal status.

However, the absolute advantage created by chemotherapy varies depending on the risk of recurrence and declines at older ages. Optimal adjuvant chemotherapy lasts 4-6 months. When choosing a treatment, attention should be paid to side effects of the drug and other diseases of the patient. Most of the chemotherapeutic side effects are temporary; hair loss, nausea, vomiting, weakness, diarrhea or constipation, menstrual irregularities, nail and skin changes. Also, it should be kept in mind that there is a risk of early menopause among side effects due to chemotherapy. One of the most discussed issues during treatment is the measures to be taken against infectious diseases. During treatment, the risks of transient bone marrow suppression and the infectious diseases it may cause should be kept in mind. Weekly blood counts are monitored especially in the newborns, and medications are used to stimulate bone marrow functioning if necessary. When body temperature is elevated, appropriate antibiotics should be used.

Among chemotherapy-completed patients, hormone receptors are recommended for hormone therapy after chemotherapy is over. The disease, which has not entered menopause, has been given tamoxifen, a selective antiestrogen for 5 years. In addition, women under 40 years of age, for at least 2 years, ovarian function to stop temporarily drugs are used. Despite the availability of tamoxifen in the adjuvant hormone treatment of menopausal patients, a different antiestrogen treatment option under the title of aromatase inhibitor is also presented. There are three types of aromatase inhibitors we use today; anastrazole, letrozole and exemestane. Aromatase inhibitors are planned to be used as extended therapy for 5 years, either after 5 years alone, 2-3 years after tamoxifen treatment for 2-3 years, or 5 years after completion of tamoxifen treatment. Regular use of gynecological examinations during the use of these drugs, yearly control of patients for osteoporosis, and in particular serum cholesterol levels following aromatase inhibitors are required. It should be kept in mind that tamoxifen-induced liver lubrication, fever, very rarely cervical cancer, vascular occlusions and visual disturbances may occur. Those treated with an aromatase inhibitor should be aware that muscle and bone pain may occur and may increase the risk of osteoporosis, increase blood cholesterol levels, fever and sweating.

In addition to chemotherapy in the treatment of early stage (stage I and stage II) breast cancer, appropriate disease radiotherapy is also recommended. All patients undergoing breast-conserving surgery, those undergoing metastasis to the axillary lymph nodes, or those with a tumor diameter greater than 5 centimeters or who have been found to have spread to the skin are eligible candidates for radiotherapy. Radiotherapy improves regional control of the disease and contributes to survival. With the newly developed radiotherapy planning and application devices, 3-dimensional planning is made, it is possible to protect the organs in the chest such as the lung and heart and to perform radiation treatment and to protect the side effects of the skin.

Cosmetic and functional problems do not occur after radiotherapy. It has been shown that applying radiotherapy for 3 weeks instead of 6 weeks in women over 65 years increases the quality of life and the results are good. In addition, partial breast irradiation has begun for selected patients with small tumors and no spread to the axillary lymph nodes.

Patients who are admitted with distant organ metastasis or who have metastases during follow-up are also treated by looking at tumor characteristics, metastatic region and age and menopausal status of the patient. In these patients, defined as stage IV disease, different treatment modalities are proposed according to organ functions.

These can be listed as chemotherapy, hormone therapy, biological treatments and radiotherapy. In the treatment of metastatic disease, importance is given to good quality of life and treatment planning is done by paying attention to this. It is preferred to start treatment with hormone treatment in case of breast cancer with hormone receptor. These drugs include tamoxifen, LHRH analogues, aromatase inhibitors, antiestrogen drugs such as fulvestrin, progesterone derivatives. Various cytotoxic drugs are used alone or in combination with two or three drugs. When choosing treatment, care is taken to use drugs compatible with each other. Chemotherapy with a single drug is recommended in patients with no obvious complaints, whereas in patients with more complaints, multiple drug treatments are preferred. Patients with HER2 / neu oncogen expression, trastuzumab in addition to chemotherapy, and biological therapies to target trastuzumab resistance to lapatinib.

Despite highly effective treatments for metastatic breast cancer treatment, almost all of the patients relapse again, resulting in treatment resistance. Trastuzumab increased the life span by 50% from AntiHER2 treatments. However, the disease can still progress under treatment. Today's standard approach is to continue antiHER2 treatment when the disease progresses; either continue the trastuzum and change the medicine next to it, or start a new antiHER2 medication with chemotherapy. For this purpose, lapatinib has been on the agenda. When trastuzumab and lapatinib, which block HER2 oncogenes from different pathways, are used together, they are more successful than lapatinib alone.

Radiotherapy is applied to painful metastases and brain metastases. Significant symptom control is achieved with appropriate pain relievers. It is necessary to support the elements that affect the quality of life such as pain, nutrition and psychological problems starting from the beginning stage.

It is very important for the cancer patient to have a balanced and balanced diet during the treatment period. Especially it is recommended to wash well, if possible peeled fresh fruits and vegetables peeled. The use of these food items during the season is a valid recommendation for all of us. In terms of balanced nutrition, it should be understood that the intake of protein, carbohydrates and fats in certain proportions, the consumption of vegetable oils and vegetable proteins as much as possible. In addition, it is recommended to provide regular physical activity and sports, especially in the prevention of breast cancer.

Today, under the light of the developments in molecular oncology, considerable steps have been taken in adjuvant treatment of breast cancer, which is increasing in frequency. With the development of targeted therapies and new technologies, the treatment of breast cancer is much more successful. However, it is necessary to be aware of the fact that a metastatic breast cancer is treated as chronic diseases and that the treatment requires continuity.