Pivotal progress in triple-negative breast cancer | ASCO 2026

A change in the tone of the TNBC conversation was evident in a session on May 30 at the 2026 meeting of the American Society of Clinical Oncology (ASCO) focused on progress in treating this type of breast cancer. Three physician researchers provided updates in progress in TNBC by stage. In contrast to how TNBC was discussed just a decade ago, the presentations focused on new treatment protocols across all stages of the disease as well as curative options for early-stage TNBC.

The challenge of TNBC

TNBC is defined by what it lacks. Triple-negative breast cancers do not test positive for hormone receptors (estrogen or progesterone) or the protein HER2.

The past several years have seen new drug approvals in TNBC, but have also raised new questions. Among people with early-stage TNBC, who will respond well to treatment? How can doctors identify these patients? How and when are drug therapies best given for maximum impact at all stages? How best to maintain quality of life while still treating effectively? The new research findings discussed in this session offer some insight into potential answers to these questions.

For stage I TNBC, balancing risk and benefit

Up to one-third of triple-negative breast cancers are diagnosed at stage I. The five-year prognosis for these cancers is very favorable, as small tumors generally respond well to treatment. TNBCs are identified as low or high risk, yet doctors still have little ability to predict which cancers will return.

Research presented at ASCO focuses on when and how to use drug therapies, as well as finding biomarkers and other tools to guide treatment decisions.

Chemotherapy in the form of anthracyclines is often given before surgery, yet it is not needed for many people with stage I disease. These very potent drugs can cause side effects that affect quality of life and increase risk of serious health events. Several studies are exploring ways to maintain cure rates with less toxic treatment. At the same time, biomarker research in stage I TNBC tries to understand which tumors to treat more or less aggressively.

Targeting immune activity

One biomarker is the level of tumor-infiltrating lymphocytes (TILs) in a tumor. This tells us how that cancer is likely to interact with a patient’s immune system. The ongoing OPTimal, ETNA, and TIL-CHOICE trials study the role of TILs in stage I TNBC.

Tumors with TILs greater than 50% have a lower risk of recurrence because the patient’s own immune system is more engaged. In stage I TNBC, this group has over a 90% five-year recurrence-free survival, distant-free survival, and overall survival without chemotherapy.

The NeoSTOP and WSG-ADAPT-TN studies, discussed at Saturday’s session, both support not using anthracycline-based chemotherapy before surgery in certain patients. The ongoing SCARLET (SWOG 2212) study is testing the use of a shorter chemo-immunotherapy regimen without anthracyclines based on TIL status.

Other trials are testing the use of PARP inhibitors before surgery in BRCA-positive TNBC to avoid chemotherapy altogether.

Targeting cancer division

Proliferation rate is another biomarker that measures how fast cells divide and spread. Low proliferation and high TILs together are associated with better outcomes, even when residual disease remains after neoadjuvant chemotherapy.

Other ongoing studies incorporate imaging or lab tests to evaluate how the cancer is responding to treatment and how to best adapt treatment plans based on those results.

TILs and proliferation rate may be biomarkers that we could use to determine whom to treat with which type of chemotherapy.

Future approaches to treatment will likely incorporate all of these strategies to help understand as much as possible about the tumor and how to treat it.

Immunotherapy benefits confirmed for stage II and III TNBC

Finding the most effective treatments for stage II and stage III TNBC is key to helping prevent the cancer from coming back.

The results of the KEYNOTE 522 clinical trial support the use of pembrolizumab (Keytruda) immunotherapy with chemotherapy before and after surgery in stage II and III TNBC. This combination therapy has been the standard of care since 2021.

The final report from this study, presented on Saturday at ASCO, confirms with a full seven years of data that the addition of immunotherapy to chemotherapy improved event-free survival at 84 months by 8.5% (78.3% vs. 69.8%) and overall survival by 7.9% (85.1% vs. 77.2%). KEYNOTE 522 is very significant because chemotherapy after surgery alone is not effective in this group.

Ongoing research also focuses on:

• Better options for tumors that still have signs of cancer after pre-operative treatment with chemotherapy or immunotherapy
• The use of drugs, especially antibody drug conjugates (ADCs), in early-stage disease that have been effective against metastatic TNBC
• Whether immunotherapy is needed after surgery: The OptimeICE-PCR study, enrolling now, will test immunotherapy in people who achieve a pCR (pathologic complete response) after neoadjuvant chemotherapy.
• Tumor freezing (cryoablation): One study showed that combining this with immunotherapy improved cure rates by almost 10% compared to the use of chemotherapy alone.
• Radiation combined with immunotherapy before surgery, including favorable results of the PEARL study
• New treatments including copper chelation, targeted therapies, and new immune strategies. Examples of promising drugs being developed and tested include the ADC emiltatug ledadotin (Emi-le) and the bispecific antibody drugs pumitamig and ivonescimab.

Metastatic TNBC

In approximately one-third of people with early TNBC, the cancer will ultimately return as metastatic triple-negative breast cancer (mTNBC).

Metastatic TNBC has fewer treatment options than other types of breast cancer; however, targeted therapies, immunotherapy, and a changing understanding of HER2 positivity offer hope and options. A robust research effort focuses on new drug development, creative combinations and sequencing of therapies and better ways to predict and assess response to therapy to extend life for as long as possible.

Using the most effective drugs as the first line of therapy is critical in mTNBC, as half of patients will not live long enough to try another treatment. Tests for biomarkers, especially PDL-1 and BRCA, determine the treatment path. A PDL-1 result can be positive or negative (more or less than 10). The PDL-1 protein is active in the body’s immune response. Tumors that test positive are more likely to respond to immunotherapy in the form of pembrolizumab. People whose tumors are negative for PDL-1 may still receive immunotherapy through a clinical trial.

The recent approval of datopotamab deruxtecan (Datroway) introduces a new first option for tumors that are negative for PDL-1. Participants in the TROPION-Breast02 trial continued an average of 5.2 months longer on this medicine compared to participants who were given chemotherapy. The drug extended life by five months as well (23.7 months vs. 18.7 months). The ADC sacituzumab govitecan (Trodelvy) is recommended by NCCN guidelines as a first option for this group as well, but FDA approval for this use is still pending. It is also offered as a second- and third-line option in TNBC.

PARP inhibitors continue to be a standard treatment for anyone who tests positive for an inherited BRCA mutation. Studies also support their use in people who develop, rather than inherit, BRCA mutations and people who inherit the PALB2 gene. Some people with TNBC may have HER2 levels high enough to qualify for anti-HER2 therapy.

Four ADCs are now approved for TNBC, as they have proven to be more effective than chemotherapy in controlling mTNBC. Research shows that the second ADC is often less effective, so it is very important to determine how to choose the most effective drug first.