Hormone-Positive Her2-Negative Metastatic Breast Cancer: Decision Making in Real Clinical Practice

Abstract

Breast cancer (BC) is the most common female cancer and the first leading cause of cancer death in women. Luminal phenotypes represent about 70% of this disease. Treatment for metastatic hormone-dependent HER2-negative breast cancer in most cases involves various lines of endocrine therapy since their sequential use improves overall and relapse-free survival while maintaining a high quality of life. Disease progression during such therapy may be associated with the development of primary or secondary resistance to the treatment. The reason for the secondary resistance is both a mutation of receptors for steroid hormones and activation of new signaling pathways. The study of these mechanisms has led to the creation of highly effective drug combinations for the treatment of hormone-positive HER2-negative metastatic breast tumors. To date, clinical trials of three agents from the group of cyclin-dependent kinases has been developed and successfully completed: palbociclib, ribociclib and abemaciclib. These agents in combination with non-steroidal aromatase inhibitors or estrogen receptor antagonists in randomized clinical trials increased direct treatment efficacy, overall survival and progression-free survival rates. Clinical case of a menopausal patient with metastatic hormone-positive HER2-negative breast cancer with visceral metastases who received successive chemotherapy and a combination of the highly selective oral kinase inhibitor CDK4\6 ribocyclib with the aromatase inhibitor letrozole allowed to achieve a response to therapy for 27 months with CR for 8 months. The safety profile was satisfactory; side effects included grade 2 neutropenia, grade 1 arthralgia, grade 1 hyperglycemia and grade 1 increase in urea which did not had an adverse effect on the patient's quality of life.

Antitumor efficacy of liposomal doxorubicin hydrochloride in combination with tamoxifen. Experimental study

“…1). We recorded a significant inhibition of tumor node growth in the second group of rats on the 18th day from the beginning of the experiment compared to the first and third groups: 36604.90, 71652.26 and 69781.11 mm 3 , respectively (p<0.05). We also noted by the end of 3 weeks of the experiment the formation of a tumor regression tendency in the 2 nd and 3 rd groups of animals, which was reliably maintained until the end of observation ( Fig.…”

“…use adjuvant chemotherapy to achieve several goals: reducing the volume of the primary tumor; reducing the size and number of affected lymph nodes; increase in the number of conservative surgical interventions; elimination of distant micrometastases, etc. [3,6,7].…”

“…The number of lung metastases in rats on 30 th days of the study hydrophilic polymers of methoxypolyethylene glycol (liposomes) in contrast to non-liposomal doxorubicin hydrochloride. This creates an advantage for the first drug, since the protection of the molecule from the reaction of the host phagocytic system is formed, which allows extending the time of circulation of the cytostatic substance in the bloodstream and ensuring its higher concentration in the tumor tissue[3]. Fukuda A. et al claim that liposomal doxorubicin hydrochloride causes less pronounced myelosuppression, cardiotoxicity, and alopecia compared to non-liposomal doxorubicin[9].…”

Prognostic role of clinical and biological factors and parameters of hormonal profile in patients with primary inoperable HER2-negative breast cancer

“…Для пациенток с гормон-позитивным HER2-негативным РМЖ в менопаузе, у которых наблюдается прогрессирование заболевания после эндокринотерапии тамоксифеном через 2 года, появилась новая опция лечения с применением препаратов группы высокоселективного ингибитора киназ CDK4/6 и ингибиторов ароматазы. У больных, получавших указанную выше комбинацию противоопухолевых лекарственных препаратов, по данным литературы, достигнут длительный ответ на терапию 27 мес, с достижением полного ответа на лечение в течение 8 мес [10].…”