Overview of recent advances in metastatic triple negative breast cancer

Abstract

Metastatic triple negative breast cancer (TNBC) has an aggressive phenotype with a predilection for visceral organs and brain. Best responses to chemotherapy are predominately in the first line. Recent studies have demonstrated improved progression free survival with the combination of atezolizumab/pembrolizumab and chemotherapy in programmed death-ligand 1 positive metastatic TNBC. However, a recent trial in a similar population showed no benefit for atezoli-zumab and paclitaxel which led to a Food and Drug Administration alert. Two phase III trials (OLYMPIAD and BROCADE3) demonstrated a benefit in progression free survival (PFS) but not overall survival in patients with BRCA-associated metastatic TNBC treated with Olaparib or Talazoparib respectively. For those treated with Talazoparib, the time to deterioration in health related-quality of life was also longer compared to chemotherapy. The BROCADE3 trial demonstrated that the combination of a platinum and veliparib increased PFS in first-line metastatic TNBC but at the cost of increased toxicity. There are no head-to-head comparisons of a poly (adenosine diphosphate-ribose) polymerase inhibitors (PARPi) and platinums. There are unanswered questions regarding the role of PARPi maintenance after platinum therapy as is standard of care in BRCA-associated ovarian cancer. Other areas of therapeutic interest include targeting aberrations in the phosphoinositide 3-kinase pathway, protein kinase B, mammalian target of rapamycin or utilising antibody drug conjugates. This review focusses on recent and emerging therapeutic options in metastatic TNBC. We searched PubMed, clinicaltrials.gov and recent international meetings from American Society of Clinical Oncology, San Antonio Breast Cancer Conference and the European Society of Medical Oncology.

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“…In addition, TNBC is more likely to occur in young female patients and is highly metastatic. It can relapse within 3 years and metastasize to the brain, liver, and lungs (15). To detect the metastasis of TNBC at an early stage and improve the prognosis and survival rate of patients, researchers need to gain greater knowledge and understanding of metastasis-related signaling pathways and biomarkers.…”

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“…TNBC has the worst prognosis of all the BC subtypes and is treated with systemic chemotherapy to which it responds better than other subtypes. Unfortunately, the use of traditional cytostatics (cisplatin, paclitaxel) is limited by numerous side effects (bone marrow damage, severe renal failure, peripheral neuropathies), as well as the occurrence of resistance to therapies [ 31 , 32 , 33 , 34 ]. Due to the lack of recognized molecular targets for therapy, TNBC is an object of interest for clinical trials with novel treatment approaches [ 13 ].…”

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“…Triple negative breast cancer (TNBC), a subgroup of breast cancer, is often found as high grade of invasive ductal carcinoma with aggressive behavior ( O'Reilly et al, 2021 ). The incidence rate of TNBC accounts for approximately 15%–20% of breast cancers ( Chen et al, 2021 ; Chowdhury et al, 2021 ).…”