Triple negative breast cancer (TNBC) is classified by its lack of expression of oestrogen/progesterone and human epidermal growth factor receptor 2 (HER2) status. This subtype of breast cancer is highly proliferative and therefore usually responsive to chemotherapy. It accounts for 10-15% of all breast cancer diagnoses, is more commonly diagnosed in women aged under 40 and associated with inherited mutations such as BRCA1/2. Compared to other breast cancer subtypes, TNBC is more likely to distantly recur in visceral sites such as liver, lung, and central nervous system whereas hormone positive disease more commonly recurs in bone. TNBC has a worse short-term prognosis with a higher risk of recurrence within the first 2 years after diagnosis.
For patients with early stage TNBC, the majority will receive neoadjuvant chemotherapy with the addition of immunotherapy for those with stage II/III disease. The goals of this treatment are to reduce the risk of distant recurrence, induce downstaging, reduce extent of surgery, assess response to systemic treatment which then assists with guiding adjuvant therapies. Adjuvant treatment depends on response to neoadjuvant therapy as well as breast cancer susceptibility gene (BRCA) mutation status.
Unfortunately, up to 30% of patients will develop distant metastatic disease after their early-stage diagnosis. Metastatic TNBC treatment is guided by tumour burden, previous neoadjuvant/adjuvant therapies received, BRCA status and programmed cell death ligand 1 (PD-L1) status. Chemotherapy in combination with immunotherapy for patients with a PD-L1 combined positive score (CPS) >10 or chemotherapy alone if the CPS score <10 is indicated for first line treatment. For patients with a BRCA mutation, poly (ADP-ribose) polymerase (PARP) inhibitors have shown efficacy but are not currently listed on the pharmaceutical benefits scheme (PBS). Antibody drug conjugates (ADCs) such as Sacituzumab Govitecan in the second line setting has shown efficacy compared to standard of care chemotherapy agents. Despite this, the prognosis for patients with metastatic TNBC remains poor compared to advanced hormone positive disease. Further research into predictive and prognostic biomarkers as well as utilising differing combinations of chemotherapy, immunotherapy and ADCs are currently being investigated to further improve patient outcomes.