Cardiotoxicity of breast cancer drug treatments

Fig. 1. An overview of breast cancer treatment by subtype. HR+ (ER+/PR+) = hormone positive breast cancers; HER2+ (human epidermal growth factor receptor 2 positive breast cancer); TNBC = triple negative breast cancer; ET= endocrine therapy; ChT = chemotherapy; RT = radiotherapy; OFS = ovarian function suppression. Treatment shown for early and metastatic breast cancer with fundamental differences explained in terms of goals of treatment and use of the different therapies involved. T1 (T1a, T1b, and T1c): tumour is 2 cm or less. T2: tumour is more than 2cm but less than 5cm. N0: cancer not spread to nearby lymph nodes. N+: cancer spread to the nearby lymph nodes. Image created in CorelDRAW.

Fig. 2. PRISMA flowchart showing the study selection process to identify relevant clinical trials reporting on the cardiac safety of breast cancer treatments. Image created in CorelDRAW.

Fig. 3. An overview of the mechanisms underlying treatment-related cardiotoxicity. Anthracyclines can induce cardiotoxicity by upregulation of death receptors in cardiomyocytes. Alkylating agents directly bind to DNA and cause DNA strand breaks. Taxanes can stimulate histamine receptors in cardiac cells causing damage. HER2 targeted therapy e.g. Trastuzumab can cause cardiac cell disruption by interfering with the ErbB/NRG-1 signalling pathway and affect myocyte development. Endocrine therapy such as Aromatase Inhibitors can cause cardiotoxicity by reducing the amount of endogenous oestrogen which increases the risk of CVD (cardiovascular disease). Image created using Inkscape.

Fig. 4. Mechanism of action of Trastuzumab Deruxtecan on breast cancer cells. Trastuzumab (a monoclonal antibody) is covalently linked to Deruxtecan. Trastuzumab attaches to the HER2 protein and delivers the cytotoxic drug directly to the cancerous cell. The cell internalises the cytotoxic compound, killing the cell and releases it to neighbouring cells in a phenomenon called the bystander effect. Image created using Inkscape.