Despite Progress in TNBC, More Biomarkers Are Needed to Improve Outcomes

Despite progress in treating triple-negative breast cancer (TNBC), further biomarkers are required to enhance patient outcomes. While immunotherapy has become more prevalent in TNBC management, treatment decisions still depend on a limited number of validated biomarkers. Pembrolizumab, a PD-1 inhibitor, has gained approval for various settings, including neoadjuvant use for high-risk early-stage TNBC and first-line metastatic treatment in combination with chemotherapy.

However, PD-L1, a biomarker indicating potential benefit from pembrolizumab, is not universally applicable, showing varying predictive value across different settings and assays.

Other targeted therapies for TNBC include PARP inhibitors for BRCA1/2 germline mutations and HER2 expression, as well as trastuzumab deruxtecan for HER2-low status. Yet, these treatments are not universally approved, with some awaiting further data. Emerging biomarkers, such as NTRK fusions and tumor-infiltrating lymphocytes, show promise in guiding therapy. Additionally, circulating tumor DNA (ctDNA) is being explored for detecting residual disease, estimating recurrence risk, and monitoring treatment response.

Prospective studies are ongoing, investigating ctDNA's potential to guide treatment decisions. Dynamic biomarkers measured during treatment may prove more informative than single pretreatment biopsies. However, there remains a need for additional biomarkers to effectively identify patients who will benefit from immunotherapy, determine appropriate escalation or de-escalation of treatments, and overcome resistance in TNBC.