Triple Negative Breast Cancer: Updates on Classification and Treatment in 2021

Abstract

Breast cancer (BC) is the most common malignancy affecting women. It is a highly heterogeneous disease broadly defined by the differential expression of cell surface receptors. In the United States, triple negative breast cancer (TNBC) represents 15 to 20% of all BC. When compared with other subtypes of BC, TNBC tends to present in younger women, and has a higher mortality rate of 40% in advanced stages within the first 5 years after diagnosis. TNBC has historically had limited treatment options when compared to other types of BC. The mainstay of treatment for TNBC remains cytotoxic chemotherapy despite the emergence of new biologic and targeted agents. Defining the specific tumor molecular profile including PDL-1 and androgen receptor testing is expanding treatment options in the clinical setting. Identifying more targetable, novel biomarkers that may better define therapeutic targets or prognostic markers is currently underway. TNBC nomenclature is expected to be updated in favor of other nomenclature which would help direct therapy, and further redefine TNBC's heterogeneity. Given the continuous advances in the field of TNBC, this review assesses the latest developments in basic characterization, subtyping, and treatment of TNBC, including novel drug developments with antibody-drug conjugates, immune checkpoint inhibitors, PARP inhibitors and androgen receptor targeted agents. Future trials are necessary in the face of these innovations to further support the use of new therapies in TNBC and the detection of the appropriate biomarkers.

Keywords: Poly (ADP-ribose) polymerase inhibitors; immune checkpoint inhibitors; immunoconjugates; triple negative breast neoplasms.

Figure 1

TNBC classification over the years.

Figure 2

Treatment of metastatic triple negative breast cancer. PARP = Poly (ADP-ribose) polymerase PD-L1 = Programmed death-ligand 1 TMB = tumor mutational burden MSI = microsatellite instability. In general, the first line treatment for mTNBC depends on the PDL-1 status. If the status is confirmed to be PD-L1 +ve, then the patient is treated with Pembrolizumab along with a second agent that is determined by the duration of treatment (12 months cutoff) from adjuvant chemotherapy. If the status is confirmed to be PD-L1 −ve, then the patient is treated with chemotherapy if no BRCA mutation is detected. PARPi inhibitors can be used when a BRCA mutation is detected irrespective of PD-L1 status. The second line of treatment is Sacituzumab Govitecan or other novel ADCs or checkpoint inhibitors.