The Present and Future of Clinical Management in Metastatic Breast Cancer

Abstract

Regardless of the advances in our ability to detect early and treat breast cancer, it is still one of the common types of malignancy worldwide, with the majority of patients decease upon metastatic disease. Nevertheless, due to these advances, we have extensively characterized the drivers and molecular profiling of breast cancer and further dividing it into subtypes. These subgroups are based on immunohistological markers (Estrogen Receptor-ER; Progesterone Receptor-PR and Human Epidermal Growth Factor Receptor 2-HER-2) and transcriptomic signatures with distinct therapeutic approaches and regiments. These therapeutic approaches include targeted therapy (HER-2+), endocrine therapy (HR+) or chemotherapy (TNBC) with optional combination radiotherapy, depending on clinical stage. Technological and scientific advances in the identification of molecular pathways that contribute to therapy-resistance and establishment of metastatic disease, have provided the rationale for revolutionary targeted approaches against Cyclin-Dependent Kinases 4/6 (CDK4/6), PI3 Kinase (PI3K), Poly ADP Ribose Polymerase (PARP) and Programmed Death-Ligand 1 (PD-L1), among others. In this review, we focus on the comprehensive overview of epidemiology and current standard of care treatment of metastatic breast cancer, along with ongoing clinical trials. Towards this goal, we utilized available literature from PubMed and ongoing clinical trial information from clinicaltrials.gov to reflect the up to date and future treatment options for metastatic breast cancer.

Understanding Breast Cancer Aggressiveness and Its Implications in Diagnosis and Treatment

“…BC aggressiveness is associated with metastasis, relapse, and high mortality rates. The aggressiveness of BC can vary according to the disease stage and other related factors such as glucose metabolism, hormone receptors, and gene signature expression [ 1 ]. Clinical characteristics of BC show that it is intrinsically a heterogeneous complex of diseases with specific molecular subtypes.…”

“…Clinical characteristics of BC show that it is intrinsically a heterogeneous complex of diseases with specific molecular subtypes. Markers for each subtype are characterized by histological, genomic, and gene expression analysis levels, each of which provides signatures that can be used to categorize breast cancers as luminal A (proximal), luminal B (distal), luminal-HER-2, and basal-like phenotypes [ 1 ].…”

“…In addition, the absence of these receptors limits treatment options for TNBC patients. While TNBC can resist hormone- and immunotherapy, it is often sensitive to chemotherapeutic agents and radiotherapy [ 1 ].…”

HS‐10352 in hormone receptor‐positive, HER2‐negative advanced breast cancer: A phase 1 dose‐escalation trial

“…Hormone receptor (HR)‐positive, human epidermal growth factor receptor 2 (HER2)‐negative subtype accounts for over two‐thirds of all breast cancer cases 2,3 . The current standard of care for HR‐positive, HER2‐negative advanced breast cancer (ABC) involves endocrine therapy, with or without cyclin‐dependent kinase 4/6 (CDK4/6) inhibitors 4–6 . PIK3CA mutations are present in approximately 40% of patients with this subtype, 3,7 with a higher prevalence in the Chinese population than Whites 8 .…”

DNA Mismatch Repair System Imbalances in Breast Adenocarcinoma

“…For this reason, BrCa categorization based on these proteins is critical for optimal oncological handling by designing and applying specific targeted and chemotherapeutic regimens. Besides them, new immunotherapy strategies are applied alone or in combination with radiotherapy (8,9). HER2/ER/PR gene expression signatures are critical for the development of sporadic BrCa, whereas BrCa genes, such as BRCA1/2, are involved in hereditary/familial cases (10,11).…”