Abstract
Simple SummaryBreast cancer is a heterogeneous disease, which encompasses several subgroups of entities widely varying by clinical-pathological features. Triple negative breast cancer is characterized by a particularly aggressive biological behavior. The administration of chemotherapy has long represented the most efficacious weapon in combating triple negative breast cancer in both its initial and late phase of development. A pivot point has been recently reached throughout the approval of the immunotherapic agent atezolizumab in combination with chemotherapy as first-line treatment for programmed-death ligand 1-positive, unresectable locally advanced, or metastatic triple-negative breast cancer. Results from the registrative trial, IMpassion 130, have increasingly fueled the flourishing of studies of immune-checkpoint inhibitors in the early stage of triple negative breast cancer development. We critically interpret results from the most recent literature in light of relevant issues of methodological nature and also present a quantitative summary of data from the inherent trials. Future directions are also highlighted.Chemotherapy based on the sequential use of anthracyclines and taxanes has long represented the most efficacious approach in the management of early-stage, triple-negative breast cancer, whose aggressive behavior is widely renowned. This standard chemotherapy backbone was subsequently enriched by the use of carboplatin, based on its association with increased pathologic complete response and efficacy in the metastatic setting. Following the results from the IMpassion130 trial, the recent approval of the immunotherapic agent atezolizumab in combination with chemotherapy as first-line treatment for programmed-death ligand 1-positive, unresectable locally advanced, or metastatic triple-negative breast cancer increasingly fueled the flourishing of trials of immune-checkpoint inhibitors in the early setting. In this work, we review the most recent inherent literature in light of key methodological issues and provide a quantitative summary of the results from phase II–III randomized trials of immunotherapic agents combined with chemotherapy in the setting of interest. Hints regarding future directions are also discussed.
Highlights
Triple-negative breast cancer (TNBC) is widely recognized as the most aggressive and lethal breast cancer (BC) subtype
Residual cancer burden (RCB) quantification in the pathological specimen helps identify long-term outcomes, with greater residual disease associated with worse relapse-free and overall survival (OS) in the TNBC population [9]
Consistent results in support of the efficacy of anti-PD-(L)1 agents combined with chemotherapy recently emerged from three phase I/II trials, further confirmed by a randomized, double-blind phase III trial, which showed a significant and clinically relevant benefit from pembrolizumab in the neoadjuvant setting, a longer follow-up is needed to better outline the actual survival benefit
Summary
Triple-negative breast cancer (TNBC) is widely recognized as the most aggressive and lethal breast cancer (BC) subtype. Within the TNBC category, gene-expression analysis unveiled distinct molecular subtypes differing in expression signatures and ontologies, shedding light on the existence of the molecular mechanisms underlying complex diseases and involving different patterns. Gaining knowledge concerning such mechanisms may help to identify novel targets and efficaciously enlarge the therapeutic armamentarium currently available to TNBC patients [3,4,5]. Pathological complete response (pCR) after neoadjuvant chemotherapy is able to predict long-term survival outcomes and is accepted as a surrogate endpoint in early-stage TNBC clinical trials [6,7,8]. Residual cancer burden (RCB) quantification in the pathological specimen helps identify long-term outcomes, with greater residual disease associated with worse relapse-free and overall survival (OS) in the TNBC population [9]
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