THE USE OF DOCETAXEL IN VARIOUS LINES OF CHEMOTHERAPY FPR BREAST CANCER

Full Text

Relevance. Breast cancer (breast cancer) ranks first in morbidity and mortality from malignant neoplasms among women worldwide. According to experts from the World Health Organization (WHO), over 2.2 million cases of this disease were registered in 2020. The etiology has not been fully identified and remains the object of study. According to scientists at the Dana-Farber American Cancer Institute, the initiation of breast cancer is caused by transformative (genetic and epigenetic) events in one cell. The subsequent progression of the tumor is due to the accumulation of additional genetic changes in combination with clonal expansion and selection [1].
The main method of treating this pathology is considered to be a surgical method- removal of the breast together with regional lymph nodes and pectoral muscles. However, this operation, which is difficult for patients, the purpose of which is to achieve maximum radicalism, does not always affect the natural course of the disease and does not guarantee the absence of metastases and relapse in the future [2].
Today, in addition to the surgical method, radiation therapy is used, the purpose of which is effective and safe treatment of the tumor with radiation. Safety is ensured by minimizing damage to a number of localized healthy tissues and organs.
Also, chemotherapy is used in the treatment, the basis of which is the appointment of antitumor drugs and their various combinations. The goals of chemotherapy are to control the symptoms of the disease, eliminate pain and improve well-being, increase life expectancy, reduce the risk of relapses, palliative treatment. At the initial stages of therapy, the most rational approach is to conduct consecutive lines, that is, chemotherapy courses.
Despite the large range of antitumor drugs on the pharmaceutical market, not all drugs have a wide spectrum of action. Some of them are active only in the first line of chemotherapy. With the help of a properly selected drug, remission can be achieved faster and the risk of death can be reduced. The beginning of the synthesis of taxanes served as a catalyst in the treatment of breast cancer. Taxanes belong to the group of cytostatics, the mechanism of action of which is directed at the microtubules of the mitotic spindle of division, consisting of the protein tubulin. Taxanes bind to tubulin, increase the rate and degree of its polymerization, stimulate the assembly of microtubules, stabilize the formed microtubules, prevent the depolymerization of tubulin and the decay of microtubules, and also cause the induction of independent apoptosis, thus disrupting the functioning of the cell in the mitosis phase and interphase [2].
The taxane drugs include Docetaxel (Docetaxel) – one of the main drugs chosen by oncologists for chemotherapy. The drug causes disruption of cell division in the G2 and M phases of the cell cycle, thereby inhibiting mitosis. The effectiveness of this drug has been proven in studies of clinical pictures of various forms of cancer, including breast and prostate cancer, head and neck cancer, ovarian cancer, as well as non-small cell lung cancer. Initially, the drug was developed for the treatment of breast cancer, but over time, based on the results of various studies, it can be argued that docetaxel is widely used among the treatment of other pathologies. Docetaxel is included in the standards of metastatic breast cancer therapy in adjuvant and neoadjuvant regimens both in combination with other cytostatics and in combination with anti-HER2 agents.
Goal. To analyze clinical cases of the use of docetaxel in various lines of chemotherapy in patients diagnosed with breast cancer of stages 1 and 3, as well as to evaluate the effect of the drug on the general well-being of patients.
Materials and methods. The study was conducted on the basis of the BUZ VO VOCOD in January 2023. Two clinical cases of docetaxel use in the first and eleventh lines of chemotherapy, stage 1 and stage 3 of breast cancer were studied. In one case, docetaxel was used as monotherapy, in another - in combination with other drugs. Both patients in the department underwent a Madden mastectomy, then chemotherapy was prescribed. Laboratory tests of blood, urine, biochemical analysis, coagulogram of patients were studied. Patients were also examined, medical records were analyzed, anamnesis was collected, and the general condition was compared during the course of docetaxel chemotherapy.
Results. Patient L., born in 1964, applied to the VOCODE Medical Center in 2015 with complaints of pain in the area of the mammary glands with the presence of seals. From anamnesis: previously there was no pain, the patient leads an active lifestyle, denies the presence of bad habits. There are no oncological diseases in the family, the cause of death of both parents is a pathology of the heart. Also, all family members have arterial hypotension. The patient noted early menopause at the age of 35.
Mammography was performed, in the conclusion of which the doctor noted the suspicion of a tumor.
The patient underwent an immunohistochemical study of the material. The study was carried out on slices of paraffin blocks of the tumor by immunohistochemical method using HercepTest Kits antibodies and EnVision imaging system.
The study revealed intensive staining of tumor cell cytolemmas with antibodies to HER 2-neu (3+).
The presence and expression of estrogen and progesterone proteins was assessed by calculating the percentage of stained nuclei and the intensity of expression.
Er clone 1B5 (estrogen receptors) - moderate and bright expression in 65% of nuclei
PgR clone PgR636 (progesterone receptors) - moderate expression in 2% of nuclei
Ki 67 clone MIB1 (proliferative activity) - 25% of nuclei
HercepTest Kits (Her2-neu) - (3+).
An immunohistochemical study with antibodies to E was also carried out-
Cadherin, the reaction in tumor cells is positive.
Conclusion: morphoimmunohistochemical picture of infiltrating breast carcinoma of nonspecific type G2. In the tumor, the expression of estrogen receptor proteins is high, progesterone expression is weak, proliferative activity in 25% of nuclei. Expression of Neg2-neu at the (3+) level.
According to the results, a clinical diagnosis was made: cancer of the left breast, stage 3A, T2N2M0.
Additional studies included:
UAC from 02/21/2015: gem 128, er 4.1, Leu 8.4, c 85, C03 7
OAM from 02/21/15: without pathology
BH from 02/21/15: GL 4.9, AM 48, KR 57, ASAT 15, ALAT 13
Coagulogram from 02/21/15 MNO 0.78, PTI 115%
A fine needle biopsy was performed.
Conclusion: infiltrating carcinoma G2.
In February 2015, a Madden mastectomy was performed, and a course of chemotherapy was prescribed, including combinations of drugs-taxotere and herceptin. Docetaxel was absent in these combinations. According to the results of the UAC, the level of leukocytes increased sharply.
During the treatment, another diagnosis was made-chronic pancreatitis. The chemotherapy line was extended to 7 courses. In the same year, they were able to achieve remission.
However, in 2018, metastases to the right lobe of the liver were detected during a routine medical examination. Chemotherapy with tamoxifen+ trastuzumab was prescribed. Docetaxel was still missing from this combination. Additionally, a course of remote radiation therapy was prescribed, the radiation dose was 40 Gy.
In 2019, metastases appeared in the left lateral mass of the sacrum. The patient's complaints of severe pain in this area have been noted, which have not stopped until now. They prescribed a course of chemotherapy again, changed the combination of drugs: trastuzumab + exemestane. Docetaxel was not included in the list of appointments. They changed the drugs for hormone therapy.
During the treatment, another diagnosis was made: somatotrophic anxiety pain disorder. Symptoms manifested themselves as weakness, malaise, burning pain on the palms, passing by itself. The patient noted severe itching of the skin from the drugs. She complained of pain in the peritoneum after targeted therapy. There are no mental disorders in the family. A course of neuroleptics has been prescribed.
In the summer of 2021, according to the results of a biopsy, metastases appeared in the pancreas. The eleventh line of chemotherapy was performed using a new combination of antitumor drugs: docetaxel + trastuzumab + pertruzumab. During the treatment, the leukocyte level decreased to normal, then below normal. To date, during the conversation with the patient, it was revealed: the general condition has improved, sleep and appetite have normalized-since the appointment of taxanes, the weight gain has been +11 kg. The pain in the sacrum area has decreased. The patient noted that since the appointment of docetaxel, she feels better and in her free time from therapy, she is engaged in physical labor.
Another clinical case.
The patient, born in 1968, was examined at a medical institution at the place of residence. There were no complaints about well-being. Mammography revealed a tumor localized in the left breast. With the result obtained, I applied to the VOCODE Medical Center in December 2022, where additional studies were conducted: trepan biopsy, general blood analysis, general urine analysis, biochemical tests. According to the results of the studies, the previously diagnosed cancer of the left breast, stage 1, was confirmed. The size of the tumor was 1.8x1.2 cm. No tumor growth was detected in the nipple. There was no tumor growth in the tissue of the studied 14 regional lymph nodes. In January 2023, a mastectomy operation was performed on Madden's left, and docetaxel monotherapy was prescribed, the first line. During the conversation with the patient, it was found out that docetaxel does not show side effects in this patient. The state of health, as before the diagnosis, is satisfactory.

About the authors

Polina Vladimirovna Papieva

Voronezh State Medical University named after N. N. Burdenko

Author for correspondence.
Email: polinapapieva30@gmail.com
ORCID iD: 0000-0002-5135-9326
SPIN-code: 0000-0000
ResearcherId: ГВУ-1309-2023
https://new.vestnik-surgery.com/index.php/2415-7805/user/register

Student

Russian Federation, 10 Studentskaya str., Voronezh, 394036, Russia

References