In later stages where surgery is not possible or the cancer has spread from the initial localised area, treatment is limited to chemotherapy and in some cases further targeted therapy.
Thus, triple-negative tumors may be distinguished from other breast cancer subtypes by a unique pattern of common and rare germline alterations.
[13] Although TNBC has a variety of different subtypes that may vary depending on how they are determined, to date the disease is still uniformly treated with chemotherapy although they may have additional targeted treatments.
Early stage TNBC is generally very susceptible to chemotherapy and can lead to a pathological complete response (pCR) i.e. no detectable cancer cells in the breast or lymph nodes.
Treatment depends on whether the tumour tests positive for the programmed death cell ligand 1 (PD-L1) protein or BRCA gene mutation.
The following treatment is recommended by the American Society of Clinical Oncology (ASCO) for metastatic TNBC:[23] Sacituzumab govitecan (Trodelvy) is an anti-Trop-2 antibody linked to SN-38, developed by Immunomedics Inc. (now Gilead Sciences).
[24] Sacituzumab govitecan had previously received FDA priority review, breakthrough therapy, and fast track designations.
[28] A novel antibody-drug conjugate known as glembatumumab vedotin (CDX-011), which targets the protein GPNMB, has also shown encouraging clinical trial results in 2009.
[30] An accelerated approval Phase II clinical trial (METRIC) investigating glembatumumab vedotin versus capecitabine began in November 2013, expected to enroll 300 patients with GPNMB-expressing metastatic TNBC.
[31] Three early stage trials reported TNBC results in June 2016, for IMMU-132, Vantictumab, and atezolizumab in combination with the chemotherapy nab-paclitaxel.
[32] In 2019, CytoDyn initiated a Phase 1b/2 trial with its humanized monoclonal antibody, leronlimab (PRO 140), in combination with chemotherapy following strong results in animal murine models.
On November 11, 2019, CytoDyn reported that the first TNBC patient injected under its naïve protocol (not previously treated for triple-negative breast cancer) demonstrated significantly reduced levels of circulating tumor cells (CTCs) and decreased tumor size at two-week and five-week observation intervals compared to baseline observations.
[33][34] As of 2022[update] a combination of ostarine, a selective androgen receptor modulator, and sabizabulin is under investigation in a phase II trial.
Epidemiologic and preclinical lab studies indicate that metformin has anti-tumor effects, via at least two mechanisms, both involving activation of the AMP-activated protein kinase (AMPK).
[40] Triple-negative breast cancer cells rely on glutathione-S-transferase Pi1, and an inhibitor (LAS17) shows encouraging results in a pre-clinical study.