Metastatic triple-negative breast cancer (TNBC) has been one of the most challenging breast cancer subtypes to treat, with limited targeted therapy options and poorer outcomes compared with other forms of breast cancer. However, the treatment landscape has changed rapidly in recent years as immunotherapy, PARP inhibitors, antibody-drug conjugates (ADCs), and biomarker-driven therapies continue expanding treatment possibilities.
At ASCO’s 2026 Annual Meeting, presenter Rita Nanda, MD, FASCO, Associate Professor of Medicine and Breast Oncology Program Director at The University of Chicago, discussed recent advances in systemic treatment for metastatic TNBC and how biomarker testing is shaping treatment decisions.
The presentation was part of a broader session focused on evolving treatment strategies across both early-stage and metastatic TNBC.
Chemotherapy has typically been the primary treatment option for metastatic triple-negative breast cancer. Today, clinicians have more therapy options available, making treatment selection increasingly individualized.
Dr. Nanda emphasized that selecting the most effective therapy early in the disease course is especially important because many patients may not receive multiple subsequent lines of treatment. “About half of our patients with metastatic disease don’t go on to receive another line of therapy,” she said.
Key factors influencing treatment decisions may include:
PARP inhibitors remain an important treatment option for patients with BRCA-associated metastatic triple-negative breast cancer and may also benefit select patients with PALB2 mutations or somatic BRCA alterations.
Dr. Nanda reviewed new data showing that PARP inhibitors can improve progression-free survival while maintaining quality of life compared with chemotherapy. She also highlighted ongoing research aimed at overcoming PARP inhibitor resistance and expanding their use through combination strategies.
“They are excellent drugs associated with efficacy and a wonderful quality of life,” she said.
One of the biggest shifts in metastatic TNBC treatment has been the growing use of antibody-drug conjugates (ADCs). These therapies are designed to deliver chemotherapy directly to cancer cells while limiting damage to surrounding healthy tissue. Researchers continue to evaluate how ADCs may improve outcomes for patients whose disease has progressed after prior treatment.
Researchers are actively investigating why some patients respond well to an initial ADC but receive less benefit from subsequent ADCs. Understanding resistance mechanisms may help clinicians determine which drugs to use first.
For patients with PD-L1-positive disease, in which tumor cells or surrounding immune cells overexpress the Programmed Death-Ligand 1 (PD-L1) protein, immunotherapy remains an important first-line treatment due to demonstrated survival benefits.
Researchers continue to investigate how immunotherapy may be combined with chemotherapy or other targeted treatments to improve outcomes and extend survival. However, clinicians must also weigh potential benefits against immune-related adverse events, treatment burden, and quality-of-life considerations when developing treatment plans.
Shared decision-making remains an important part of care as patients navigate complex treatment choices throughout the course of disease.
Dr. Nanda’s ASCO presentation highlighted how systemic treatment for metastatic triple-negative breast cancer is becoming increasingly guided by biomarkers that help match patients to immunotherapy, PARP inhibitors, ADCs, and other targeted therapies. As treatment options continue to expand, researchers are working to address challenges related to treatment sequencing, resistance mechanisms, and quality of life while advancing a more personalized approach to care.
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