Triple negative breast cancer (TNBC) is a biologically heterogeneous disease that is treated according to stage at diagnosis. Early steps toward treatment personalization used staging for prognostication and later incorporated residual disease burden after neoadjuvant therapy to guide adjuvant treatment decisions. Therapeutic advances, particularly with immunotherapy and poly (ADP-ribose) polymerase inhibitors, have progressed more rapidly than the ability of clinical trials to adapt accordingly, leaving many critical questions regarding treatment combinations and sequencing unanswered. Adapting neoadjuvant and adjuvant strategies according to dynamic changes in the tumor, tumor microenvironment (TME) and novel biomarkers dynamics offers a compelling framework for both treatments escalation and de-escalatation. This review traces the historical evolution of TNBC treatment, examines the challenges of tumor heterogeneity and residual disease after neoadjuvant therapy, and explores the prognostic impact of the TME. We then appraise the latest evidence on poly (ADP-ribose) polymerase inhibitors, antibody-drug conjugates, and immunotherapy in the early setting, outlining a path toward more individualized therapeutic approaches.
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