Significance and possible causes of hormone receptor expression loss in metastatic breast cancer. Phenotypic evolution of luminal BRCA1-associated breast cancer to triple negative subtype in lung metastasis and PARP inhibition strategy in early-line therapy

Current clinical recommendations indicate the need for a biopsy of a metastatic focus in metastatic breast cancer (BC), but the optimal frequency of additional molecular analysis remains unclear. The discordance of hormonal receptors (HR) between the primary tumor and metastatic foci has prognostic significance, while the transition from HR-positive BC to a triple negative phenotype is associated with a worse clinical prognosis. Acquisition of HR expression in primary triple negative BC is more favorable due to the wide range of options for HR-positive BC treatment. Over the past few years, PARP inhibitors have become an important therapeutic option for the treatment of various tumor types, including BC and luminal surrogate subtypes. However, some questions still remain unresolved, the most important of which are: what is the optimal sequence of the use of CDK4 / 6 inhibitors as part of combined hormone therapy and PARP inhibitors in luminal types of BRCA-associated BC and how effective is the strategy of PARP inhibition after the use of combined hormone therapy with CDK4 / 6 inhibitors? It is obvious that the answers to the questions can be partially obtained by performing a biopsy of the most clinically significant metastatic focus and selecting therapy according to the phenotypic surrogate subtype. A clinical case of the phenotypic evolution of HR-positive BRCA1-associated BC into a triple negative phenotype during metastasis to the lungs and the luminal phenotype of tumor metastasis in soft tissues is presented. Biopsy of the most clinically significant metastatic lesion in the lungs in this case changed the strategy of early-line therapy for estrogen-receptor-positive disease, when in the absence of a biopsy, a combined hormone therapy regimen with CDK4 / 6 inhibitors could be applied. At the same time, the strategy of using PARP inhibitor talazoparib, which has shown efficacy in all surrogate subtypes, should certainly be prescribed in the early line of therapy for BRCA-associated disease with loss of estrogen receptor expression. Despite the luminal phenotype of metastasis in the soft tissues of the back and the unknown status of bone metastases, the drug demonstrates efficacy in these cases as well. It should be noted that partial response according on RECIST 1.1 months with an improvement in the quality of life and the disappearance of pain syndrome was evaluated after 10 weeks of treatment. The response duration was an unprecedented 10 months.

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