MABs and TKIs
MABs have a range of activity. Drugs such as trastuzumab or pertuzumab control or shrink the tumour by blocking production of human epidermal growth factor. They target over-expression of HER2 receptors by binding with the receptors. This prevents cell division, stopping HER2+ cancer cell proliferation.11,12,16
Atezolizumab (in combination with paclitaxel) and pembrolizumab are indicted for triple negative breast cancer. Programmed death ligand (PD-L1 or PD1) is a protein expressed on tumour cells and tumour-infiltrating immune cells and can stop the immune response working properly. Atezolizumab and pembrolizumab block PD1 proteins, stimulating the immune system to target and kill tumour cells.16,17
Tyrosine kinase inhibitors (TKIs), such as lapatinib, neratinib, tucatinib, and pyrotinib target HER2 and other receptors of the epidermal growth factor receptor family. TKIs can block the production of cell growth factors and subsequently inhibit cell division (mitosis). Neratinib binds to HER2 receptors and reduces epidermal growth factor receptors (EGFRs). Tucatinib inhibits HER2 phosphorylation and the growth of HER2 driven cancer cells.16,19
Other protein kinase inhibitors include everolimus which blocks serine-threonine kinase activity which can be upregulated in breast cancer. It also reduces levels of vascular endothelial growth factor (VEGF), a compound which can promote vascular growth in tumour cells.16
Ribociclib, abemaciclib and palbociclib selectively inhibit cyclin-dependent kinase (CDK) 4 and 6, interfering in the signalling pathways which promote cell cycle progression and cellular proliferation, especially in ER+ tumours.16
Poly-ADP ribose polymerase (PARP) is an enzyme which helps repair damaged DNA. PARP inhibitors help prevent cancer cells from repairing their own damaged DNA leading to their cell death, and can stop cancer cells that have harmful variants of BRCA1 or BRCA2. PARP inhibitors licensed for breast cancer use include olaparib and talazoparib.20,21
Eribulin is a microtubule dynamics inhibitor, stopping the formation of tubules in the cell cytoskeleton which impairs mitosis causing cell death.16
Some patients may require bisphosphonates to treat or reduce bone damage associated with the breast cancer, or if the breast cancer has spread to the bones. Bisphosphonates can also protect against osteoporotic side effects of other treatments and reduce the risk of breast cancer returning.7,22