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Yusupova Dilnoza Bakhtiyarovna, assistant of the oncology department of the Tashkent Medical Academy Mirza Allayarovich Gofur-Okhunov, professor, Head of the Oncology Department of the Institute for Advanced Medical Studies Tashkent Medical Academy, Tashkent E-mail: www.ballack16@mail.ru
THE RESULTS OF COMPLEX TREATMENT OF BREAST CANCER IN PATIENTS OF ELDERLY AND SENILE AGE
Abstract: The incidence of breast cancer is a serious medical and social problem in the world. The course of breast cancer in the elderly has a number of features, which is associated with an increased risk of developing various kinds of complications, given the presence of comorbidities. To date, there are no specific clinical guidelines for this age group, which makes this article relevant.
Keywords: breast cancer, advanced age, complex therapy.
The incidence of the female population of breast cancer for several decades remains the 1st place in the world, and an increase in the incidence is noted not only in Europe and America, but also among countries in Asia and Africa. In recent years, significant progress has been made in the diagnosis and treatment of breast cancer due to the effective work of screening and an individualized approach to treatment [1].
Epidemiological studies indicate a slow but steady decline in the average age at which the disease is determined, however, more than half of new cases of breast cancer occur in women over 65 years of age. The average life expectancy for healthy women over the age of 70 is 15.7 years, and for 80-year-olds it is 8.6 years. It is statistically proved that breast cancer reduces the life expectancy in women 50-65 years, without significantly affecting this indicator in women 75-80 years. [2].
The extremely complex nature of malignant tumors of the mammary glands has determined the need for an accurate extended diagnosis taking into account the luminal type of the tumor, and as a result, the choice or use of all existing methods of treatment - surgical, radiotherapy, medication (chemotherapy and hormone therapy). The fundamental task in conducting adjuvant therapy is to obtain the maximum therapeutic effect and minimal side effects. [3]
Material and methods
We treated for the period from 2010 to 2018 years 111 patients with breast cancer over the age of 60 years on the basis of the city branch of the city branch of the republican specialized scientific and practical medical center of oncology and radiology. The average age of patients was 67 years.
As seen from the table, the high detectability of patients with malignant neoplasms of the mammary glands in postmenopausal maximum account for process stage II. The main
complaints at admission were the presence of a tumor in 100 patients (90%), the presence of a tumor + pain in 9 (9%) and discharge from the nipple in 2 patients (1%).
Table 1. - The distribution of patients by stage
Stage of the process Number of patients (n=111)
I 10(9%)
II 68(61%)
III 20(18%)
IV 13(12%)
Basically, the tumor was localized in the upper-outer quadrant in 55 patients (49.1%), in the lower-outer quadrant in 30 patients (26.8%), in the upper-inner in 12 (10.9%), total lesion occurred in 5 patients (4.9%), in the lower-inner quadrant in 5 (4.4%) patients and central localization was in 4 patients (3.9%).
Patients were comprehensively examined, mammogra-phy, ultrasound, cytological and histological examination were performed on all patients. The diagnosis in all patients was histologically verified. (table number 2).
Table 2.- The distribution of patients depending on the histological structure of the tumor
Histological type of tumor The number of patients (n=111)
Infiltrative ductal carcinoma 75(67%)
Infiltrative lobular cancer 11(9.4%)
Slimy cancer 8(7.4%)
Nonspecific cancer 9(8.4%)
Medullary cancer 1(1%)
Papillary cancer 3(2.9%)
Cancer in situ 4(3.9%)
Medical science
As can be seen from table № 2, infiltrative ductal carcinoma is the most common (67%), infiltrative lobular carcinoma (9.4%), least often the medullary type (1%).
In the studied group, all patients revealed comorbidities. At the same time, 80% of patients had hypertensive disease, fatty hepatosis in 66.6%, coronary heart disease in 64.6% chronic cholecystitis in 52.7%, cholelithiasis in 49.2%, chronic bronchitis in 46.2%, varicose veins of the lower extremities in 27.3%, chronic pyelonephritis in 9.4%, chronic hepatitis in 8.4%, obesity in 6.4% of patients, diabetes in 4.7% of patients. A total of 42 associated pathologies were identified. Treatment of comorbidities was carried out after consultation with specialists of the appropriate profile. Combined therapy of patients included: neoadjuvant chemotherapy mainly 4 courses, surgery, adjuvant chemotherapy (4 courses on average) and radiation therapy on a radical program.
The volume of the operation was represented by Radical mastectomy according to Madden in 86 patients (77.4%), Sectoral resection in 6 patients (5.9%), Radical resection in 10 patients (10.5%), RME according to Patty in 5 patients (3, 9%), palliative mastectomy in 2 patients (1.9%), Blokhin operation in 1 patient and simple amputation in 1 patient. The volume of the operation depended on the stage of the disease, the severity of the accompanying pathologies and the compensatory reserves of the body.
Chemotherapy was given to all patients in neoadjuvant and adjuvant regimens. Most often as a first line therapy used FAC circuit, CAF, AC, CMF as the therapy line 2 after failure of therapy 1 line or at relapse of the disease were applied schemes PA (paclitaxel, doxorubicin) Navelbin and platinum drugs capecitabine in tablet form in standard approved dosages. In 48 patients (43.2%) there was a reduction in the dose of chemotherapy drugs, taking into account age and concomitant pathologies by 10% and in 24 by 20%.
Of the patients receiving hormone therapy, there were 63 patients (56.8%), namely, 27 patients (24.3%) received tamoxifen preparation 20 mg per day, aromatase inhibitors (anastrozole 1 tablet daily) received 36 patients (32.4%) in the period from 3 to 5 years.
All patients who had metastases to bones, was appointed bisphosphonate therapy (primarily Zoldron 4 mg per month 1 time per 28 days).
Radiation therapy was also carried out to all patients in an adjuvant mode according to a radical program: 2 Gr, 5 times a week, S0D50 Gr. Patients received radiation therapy taking into account the extent of the spread of the tumor and the volume of the operation.
In 80 patients, an immunohistochemical study was performed.
Table 3.- The distribution of patients depending on the biological subtype of the tumor
Biological tumor subtype The number of patients (n = 111)
1. Luminal A-subtype 36(44.8%)
2. Luminal B-subtype HER positive 8(10.6%)
3. Luminal B-subtype HER negative 19(23.3%)
4. Triple negative 15(18.1%)
5. Non-HER Positive 2(3.2%)
As can be seen from (table 3), in women of elderly and senile age, the luminal type A was more common in 44.8% of patients, the Luminal B subtype of HER positive in 10.6%, the Lumininal B subtype of HER negative in 23.3%, Triple negative cancer in 18.1% and less likely non-membrane HER positive in 3.2% of patients.
If the patient has an immunohistochemical analysis, the treatment tactics changed depending on the luminal type of the tumor. So with luminal type A with N2-3 lymph node status, with T3-4 tumor size, with a high risk of recurrence, neoadjuvant chemotherapy was followed, followed by surgery, adjuvant chemotherapy and radiation therapy, endocrinother-apy was also added. In the case of Luminal B-subtype HER positive for endocrine therapy, the drug Trastuzumab was added to the adjuvant regimen (in parallel with the initiation of treatment with taxanes according to the scheme within 1 year). In the luminal B-subtype of HER negative, endocrine therapy was performed in all patients, while adjuvant chemotherapy was performed in the presence of risk factors. Triple negative type received treatment according to the standard scheme, but taxanes were preferred. In the non-HER positive type, adjuvant therapy included anthracyclines and taxanes + trastuzumab.
Results and discussion
Elderly patients belong to a heterogeneous group, which has its own characteristics and requires further study. Current treatment approaches are based on clinical studies that include young women with breast cancer without marked comorbidities. The results ofthese studies cannot be extrapolated to elderly patients [5]. In 2007, the FOCUS study "The Breast Cancer in the Elderly: Optimizing Clinical Guidelines Using Clinico-Pathological and Molecular Data" was launched. The FOCUS database is the largest, most detailed source of information based on a sample of elderly patients with breast cancer. The database includes 3672 patients who, in the period from 1997 to 2004, were diagnosed with breast cancer 65 years of age and older at the time of diagnosis. It has been revealed that the prognosis in women with breast cancer worsens with age, regardless of the molecular tumor subtype and treatment methods. This was confirmed by data from the National Cancer Registry, and
the cohort study "FOCUS" and the study "TEAM" [6]. It is worth noting that recommendations for the treatment ofbreast cancer in the elderly are contradictory - from radical operations to predominantly conservative therapy [4].
Literature data demonstrate a clear advantage of postoperative radiotherapy in elderly patients. Postoperative radiotherapy improves local control and overall survival. Radiation therapy can be recommended to all patients who are able to tolerate treatment and do not have associated life-threatening diseases. Hormone therapy should be offered to all patients with receptor-positive tumors as an adjunct to surgical treatment or in single mode. The selection of chemotherapy should be thorough and individual for each patient, taking into account all associated diseases and an assessment of possible complications and risks [3].
According to our research, it was revealed that women with a large number of comorbidities have a greater number of postoperative complications. The postoperative period was considered complicated if there was an abundant lymphorrhea, skin necrosis, wound suppuration, complications of therapeutic status, which required treatment. The average indicators of imparai in patients who underwent RTMs on Madden had the following: 28% insignificant, 27%, moderate, 45%.- abundant. The average indicators of lymphorrhea in patients who underwent radical resection of the mammary gland were: in 20% insignificant, in 16%, moderate, in 4%.- abundant. Skin necrosis in both groups of patients met in 24% of cases.
Evaluating the results presented, it should be noted that there is a tendency to an increase in imparai with age and a large percentage after radical surgery (in 90% of patients).
The incidence of skin necrosis also increased with age in patients who underwent Madden Radical Mastectomy. In the appearance of these complications, of course, a large role is played by the degree of vascular lesion by the atherosclerotic process and angiopathy associated with diabetes mellitus.
To calculate the 3- and 5-year survival among elderly and senile patients with breast cancer, the Kaplan-Meier method was used. Takes into account the past tense in months from the time of diagnosis (the beginning of observation) before the onset of death (critical event) as a result of the progression of breast cancer. Patients who died from other causes were censored at the time of death. The data were analyzed using MS Excel. We also studied the results of 5-year survival of elderly patients depending on the extent of surgical intervention. It was found that after radical operations, 60% lived for 5 years, and after radical resection, 56% of patients.
When analyzing the timing of the occurrence of relapse, the average duration of the disease recurrence was 25.2 months. The frequency of metastases and relapses: distant metastases appeared in the period after 63 months after the end of treatment. Most of the lungs and bones were affected. Life expectancy in months averaged 56.68 ± 2.32 months. Three and five year survival rates were 80 and 75%.
Conclusions
1. Breast cancer in elderly and senile patients is most often detected in early stage I-II in 55.2%, in 3.9% it occurs in the stage of cancer in situ.
2. In 66.7% of cases, infiltrative ductal carcinoma occurs. Such histological forms as mucous cancer (7.4%), non-specific type (8.4%) and medullary cancer (1%) were less common.
3. The luminal type A (34.8%) and the luminal type B Her 2 negative (33.3%) are most common in elderly and senile persons. These tumors differed a favorable course and prognosis of the disease. The choice of treatment method depended on the indicators of immunohistochemical research.
4. Comprehensive treatment allows to reduce the frequency of recurrence and distant metastases, increasing the life expectancy of patients. At the same time, the median survival was 56.7 ± 2.3 months, and the 5-year survival rate was 75%.
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