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Cancer is a disease that manifests itself by the increase and displacement of abnormal cells in an uncontrolled manner. The most common type of cancer in women is breast cancer. Among the risk factors that lead to breast cancer in women are the presence of breast cancer in the first-degree relatives of the family and menstruation at an early age, discontinuation of menstruation (late menopause), gaining excess weight, and taking uncontrolled hormones in menopause. The mother, daughter and sister should be considered as first-degree relatives. Genetic breast cancers are seen in approximately 10-15%. The BRCA1 and BRCA2 genes are responsible for hereditary breast / ovarian cancer syndrome. In the definition of hereditary or familial breast cancer, the presence of breast and / or ovarian cancer in many women in the family, the emergence of the disease in the 20s and 30s, and the presence of bilateral breast cancer patients are noteworthy. Women who meet this definition and who have a very high genetic risk may be recommended to have their ovaries removed after their birth and to empty the two breasts (protective mastectomy of the skin and nipple).
Early recognition of breast cancer increases the chance of healing. Screening mammography for breast cancer begins from the age of 40 years. Patients who have regular mammography can be diagnosed with cancer before the breast appears. In high-risk patients, breast ultrasonography and magnetic resonance imaging (MRI) are recommended in addition to mammography. More recently, “tomosynthesis görüntüleme imaging has been introduced. In this method, thin sections such as tomography are taken from the breast. According to the results of the clinical study, the visibility of the lesion is increased, border assessment is easier, recall and close follow-up rates are reduced and lesion localization is better performed. This imaging method, which is being used in several centers in Istanbul, increases the possibility of early diagnosis.
When the mammography is taken, the foci can be seen with tiny calcification, sometimes called “microcalcification”. These foci may be a precursor to an early breast cancer and biopsy can be performed with imaging. Although biopsies are usually performed under ultrasound guidance, biopsies can be taken from lesions detected by MR only with advanced MR technology.
Sometimes, these small foci, which cannot be noticed by hand examination, are removed by surgery by being marked with wire or radioactive material. Surgery should be performed within a few hours when marked by wire and within one day if marked by radioactive material. According to the biopsy results, the lesions that are observed to be cancerous are removed wider and the axillary lymph nodes are controlled.
Nowadays, except in some special cases, only a limited portion of the breast is removed and under the armpit, no attempt is made as large as before.
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 radioactive material into the cancerous area of the breast, to spread this dye or radioactive material under the armpit and to examine the lymph nodes (sentinel lymph node) it has stained. If no cancer cells are found in these lymph nodes, additional intervention under the armpit is not necessary. Thus, an undesirable problem such as swelling of the arm is not allowed. However, in cases where cancer cells have been transmitted to lymph nodes, all of these lymph nodes should be cleaned with a second operation, that is, axillary curage.
Sometimes the tumor can be quite large or it can cause withdrawal in the nipple, change the shape and color of the breast skin, and inflammatory symptoms. In this case, chemotherapy is applied prior to surgery, the tumor is reduced and skin changes are corrected and then given to surgery. Over the past year, successful treatment results have been announced in this patient group. Especially in patients with high-risk HER2 oncogene expression, it was shown that the tumor could completely regress with the use of targeted therapies (trastuzumab, pertuzumab, lapatinib). In the case of hormone-sensitive tumors, this tumor reduction may be performed by hormone therapy, taking into account the patient's age and other diseases.
However, if the disease has spread to other organs, that is to say metastasis, it is recommended to discontinue surgery and to apply systemic treatment and, if necessary, radiotherapy. In other words, the type of treatment is determined by considering the regional extent of the disease at the time of diagnosis (breast and armpits) and the spread to other organs. We describe this prevalence as staging of the disease.
It is accepted that breast cancer is a systemic disease and micrometastases are present even at the time of diagnosis.
Therefore, in the last 30 years, in addition to the surgical treatment of early stage breast cancer, preventive (adjuvant) chemotherapy and hormone therapy aimed at eradicating microscopic metastases has resulted in a significant increase in both disease-free survival and overall survival rates. Recently, a biological treatment has been added. In planning an appropriate adjuvant therapy, several factors are considered. Patient's age, tumor size, number of axillary metastatic lymph nodes, expression of hormone receptors (estrogen receptor, ER and progesterone receptor, PR for short), other diseases of the patient and HER2 / neu gene expression are among the parameters that determine the course of the disease and the mode of treatment. . Anti-estrogen therapy is not used in breast cancer patients without hormone receptors, and in breast cancer cases without HER2 / neu gene expression, biological treatment called trastuzumab cannot be expected. More recently, the risk profile of the disease is further elaborated 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 important support to physicians in order to guide the patients who are konusunda hesitant about adjuvant therapy ”.
The biological characteristics of the tumor are very important in the choice of treatment. Three types of breast cancer are identified by taking into account the molecular and pathological features; Disease with HER2 / neu gene, hormone receptors (ER, PR) and disease without HER2 / neu gene expression (basaloid) and ER positive disease. In adjuvant therapy, biological treatment planning is performed according to the targets. For example, hormone therapy is recommended for ER positive patients, whereas ER negative patients do not benefit from this treatment. Trastuzumab is highly effective in HER2 positive disease, but does not provide benefit in HER2 negative patients. Trastuzumab is a monoclonal antibody developed against HER-2 / neu oncogen which is detected in 20-25% of breast cancers. It is used intravenously and has proven to be useful in both preventive therapy and common disease. A more recent drug called "lapatinib" has been introduced in patients who are resistant to this drug. The mechanism of action of lapatinib is different from that of trastuzumab and has been shown to play a role in breaking resistance to hormone therapy.
The first adjuvant chemotherapy studies in breast cancer started in Europe in the 1970s with the studies of Bonadonna et al. In this study, both disease-free and overall survival were significantly increased in patients receiving chemotherapy. Subsequently, in the American study by Fisher et al., It became clear that adjuvant chemotherapy prolonged survival. Adjuvant chemotherapy decreases the risk of recurrence in breast cancer patients without any difference in age, status of lymph nodes, status of hormone receptors and menopause.
However, the absolute superiority of chemotherapy varies depending on the risk of recurrence and decreases in older ages. Optimal adjuvant chemotherapy duration is 4-6 months. When choosing treatment, attention should be paid to drug side effects and other existing diseases of the patient. Most chemotherapy-related side effects are transient; hair loss, nausea, vomiting, weakness, diarrhea or constipation, menstrual irregularities, nail and skin changes are among them. In addition, the risk of early menopause among chemotherapy-related side effects should be kept in mind. One of the most emphasized issues during treatment is the measures to be taken against infectious diseases. During treatment, the risk of transient bone marrow suppression and the risk of infectious disease that may be caused by this should be kept in mind. Weekly blood counts are monitored especially for those who are new to treatment, and if necessary, drugs that stimulate the operation of the bone marrow are used. Appropriate antibiotics should be used in cases where body temperature rises.
Among the patients whose chemotherapy has been completed, hormone receptors are recommended for hormone therapy after the end of chemotherapy. For non-menopausal patients, tamoxifen, a selective antiestrogen, is given for 5 years. In addition, medications that temporarily stop ovarian functions are used for women under 40 years of age for at least 2 years. Although tamoxifen can be used for the adjuvant hormone therapy of menopausal patients, a different antiestrogen treatment option is offered under the title of aromatase inhibitor. There are 3 types of aromatase inhibitors that we use today; anastrazole, letrozole and exemestane. Aromatase inhibitors are planned to be used either as an adjuvant therapy for 5 years alone, for 2-3 years after tamoxifen treatment for 2-3 years, or for an additional 5 years after completion of 5 years of tamoxifen treatment. During the use of these drugs, regular gynecological examinations, osteoporosis patients should be checked annually and serum cholesterol levels should be monitored especially in aromatase inhibitors. It should be kept in mind that tamoxifen-induced liver fat, flushing, uterine cancer, vascular blockages and visual disturbances may be very rare. In patients treated with aromatase inhibitors, it should be known that muscle and bone pain may occur and the risk of osteoporosis may increase, blood cholesterol levels may increase, and complaints such as flushing and sweating may occur.
In the treatment of early stage (stage I and stage II) breast cancer, in addition to chemotherapy, radiotherapy is recommended to suitable patients. All patients undergoing breast-conserving surgery, those who have metastasized to the axillary lymph nodes, or whose tumor diameter is greater than 5 centimeters or have spread to the skin, are suitable candidates for radiotherapy. Radiotherapy increases regional control of the disease and contributes to survival. With the newly developed radiotherapy planning and application devices, 3-dimensional planning is made and it is possible to perform radiation therapy by protecting organs located in the chest, such as lung and heart, and to protect the skin from side effects.
Cosmetic and functional problems are not experienced after radiotherapy. It has been shown that 3 weeks of radiotherapy instead of 6 weeks increases the quality of life and results are good in women over 65 years of age. In addition, partial breast irradiation was initiated for selected patients with small tumors and no spread to the axillary lymph nodes.
Patients who present with distant metastasis or who are found to have metastases during follow-up are treated according to tumor characteristics, site of metastasis and age and menopause status of the patient. In these patients defined as stage IV disease, different treatment modalities are recommended according to organ functions.
These include 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 made with due consideration. It is preferred to start with hormone therapy in breast cancer cases carrying hormone receptor. These drugs include tamoxifen, LHRH analogues, aromatase inhibitors, antiestrogen drugs such as fulvestran, progesterone derivatives. Various cytotoxic drugs are used alone or in combination of two or three drugs. When choosing treatment, care is taken to use a combination of compatible drugs. Single-drug chemotherapy is recommended in patients without significant symptoms, while multi-drug treatments are preferred in patients with severe complaints. In patients with HER2 / neu oncogene expression, trastuzumab in addition to chemotherapy, and those targeted to trastuzumab are added to the targeted biologic treatments called lapatinib.
In spite of the high-efficacy treatments in the treatment of metastatic breast cancer, in almost all patients, the disease recurs and resistance to the treatment developed. Trastuzumab, which is one of the antiher2 treatments, increased the life span by 50%. However, the disease may progress even under treatment. Today's standard approach is to continue antiHER2 therapy when the disease progresses; either continue trastuzumaba and change the drug next to it, or start chemotherapy with a new antiHER2 drug. For this purpose, lapatinib was introduced. When combined with trastuzumab and lapatinib, which block HER2 oncogene in different ways, it is more successful than lapatinib alone.
Radiotherapy is applied to painful metastasis sites and brain metastases. Significant symptom control is provided with appropriate analgesics. Pain, nutrition, psychological problems, such as factors affecting the quality of life starting from the initial stage of support is essential.
It is very important for the cancer patient to eat balanced and not to gain weight during the treatment. In particular, it is recommended to consume freshly washed fruit and vegetables, which are thoroughly washed and, if possible, peeled. The use of these foods during the season is a valid recommendation for all of us. When it comes to balanced nutrition, it should be understood that protein, carbohydrates and fats are taken in certain proportions and consumed as much vegetable oil and vegetable proteins as possible. It is also recommended that regular physical activity and sports be performed, especially in the prevention of breast cancer.
Nowadays, in the light of the advances in molecular oncology, very important steps have been taken in the adjuvant treatment of breast cancer. 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 that a metastatic breast cancer is treated as chronic diseases and that treatment requires continuity.
Professor Dr. Contact Nil directly Head of Medical Oncology Department American Hospital
Head of Medical Oncology Department