Analysis of the clinical efficacy of the cyclin- dependent kinase inhibitor 4/6 Abemaciclib on the clinical case of a male with hormonereceptor- positive breast cancer

Abstract

The treatment of advanced hormone- receptor-positive (HR+) breast cancer (BC) is a rather difficult task due to the emergence of resistance to the standard treatment regimen – endocrine therapy. This circumstance has led to the investigation of the role of the tumor microenvironment in the tumor response and the realization of the treatment efficiency. A new class of antitumor drugs – inhibitors of cyclin- dependent kinases 4/6 (CDK 4/6) in combination with endocrine therapy demonstrates the efficiency in prolonging the progression free survival and significantly delays the time of cytotoxic therapy administration. In this case,an additional mechanism of tumor regression, besides inhibition of cell cycle of tumor cells is the influence on the cellular component of the tumor microenvironment. Thus, according to preclinical data and results of clinical studies, an increase in the immunogenicity of the tumor and the activation of the antitumor immune response was established. This unique mechanism can be used as a strategy to increase the efficiency of antitumor drugs prescribed in later lines, as well as to increase sensitivity to immune checkpoint inhibitors. The article presents an analysis of the clinical efficiency of an aromatase inhibitor in combination with a CDK 4/6 - inhibitor Abemaciclib in male with HR-positive breast cancer. At the same time, the appointment of aromatase inhibitors in the presented clinical case is very justified due to the possible genetic violation of the metabolism of sex hormones, taking into account the pathophysiological bases of male gynecomastia. Despite the lack of an objective response to combination therapy, the patient has a long-term stabilization. This may be due to an increase in the immunoreactivity of the tumor, a cumulative effect with the development of senescence of tumor cells and subsequent apoptosis. Also, it is very likely that after the use of the CDK 4/6 inhibitor Abemaciclib, cytotoxic chemotherapy drugs will show greater effectiveness due to the actively altered immunoreactivity of the tumor microenvironment.

Keywords

• hormone- receptor-positive breast cancer
• cyclin- dependent kinase 4/6 inhibitors
• cdk 4/6 hormone therapy
• breast cancer in men
• tumor microenvironment