A Review of Systemic Treatment in Metastatic Triple-Negative Breast Cancer

Abstract

Patients with breast cancer along with metastatic estrogen and progesterone receptor (ER/PR)- and human epidermal growth factor receptor 2 (HER2)-negative tumors are referred to as having metastatic triple-negative breast cancer (mTNBC) disease. Although there have been many new treatment options approved by the Food and Drug Administration for ER/PR-positive and Her2/neu-amplified metastatic breast cancer, relatively few new agents have been approved for patients with mTNBC. There have been several head-to-head chemotherapy trials performed within the metastatic setting, and much of what is applied in clinical practice is extrapolated from chemotherapy trials in the adjuvant setting, with taxanes and anthracyclines incorporated early on in the patient's treatment course. Select synergistic combinations can produce faster and more significant response rates compared with monotherapy and are typically used in the setting of visceral threat or symptomatic disease. Preclinical studies have implicated other possible targets and mechanisms in mTNBC. Ongoing clinical trials are underway assessing new chemotherapeutic strategies and agents, including targeted therapy and immunotherapy. In this review, we evaluate the standard systemic and future treatment options in mTNBC.

Keywords: hormone receptor-negative breast cancer; metastatic breast cancer; triple-negative breast cancer.

Figure 1

Molecular classification of triple-negative breast cancer.– Abbreviations: TNBC, triple-negative breast cancer; BL, basal like; EGFR, epidermal growth factor receptor; CK, cytokeratin; ER, estrogen receptor; PR, progesterone receptor; BRCA, breast cancer susceptibility gene; HER2, human epidermal growth factor receptor 2.

Figure 2

Systemic treatment algorithm for mTNBC. Abbreviations: mTNBC, metastatic triple-negative breast cancer; ECOG PS, Eastern Cooperative Oncology Group performance status.

Figure 3

Schematic overview of the therapeutic targets that are currently being tested in clinical trials among patients with mTNBC. Abbreviations: PI3K, phosphatidylinositol 3-kinase; MEK, mitogen-activated protein kinase kinase; Akt, v-Akt murine thymoma viral oncogene; mTOR, mammalian target of rapamycin; HSP-90, heat shock protein 90; CXCR, chemokine receptor; HDAC, histone deacetylase; PARP, poly adenosine diphosphate-ribose polymerase; Trop-2, tumor-associated calcium signal transducer 2; GPNMB, glycoprotein nonmetastatic b; EGFR, epidermal growth factor receptor; VEGFR, vascular endothelial growth; PD1, programmed death 1; PDL1, programmed death ligand 1; CTLA4, cytotoxic T-lymphocyte-associated protein 4; AR, androgen receptor; CYP17A1, cytochrome P450 17A1; CSF1R, colony-stimulating factor 1 receptor; JAK1/2, janus kinase 1 and 2; Sine XPO1, selective inhibitor of nuclear export exportin 1; VDR, vitamin D pathway receptor genes; HMGCR, HMG-CoA reductase; RAS, rat sarcoma; RAF, B-raf and v-Raf murine sarcoma viral oncogene homolog B; ERK, extracellular signal-regulated kinases; STAT, signal transducer and activator of transcription; GRB2, growth factor receptor-bound protein 2; TNBC, triple-negative breast cancer.