Dr Natsuhara on Treatment Advances and Research Considerations in TNBC

Kelsey H. Natsuhara, MD, a health sciences clinical professor and medical oncologist at the University of California, San Francisco Helen Diller Family Comprehensive Cancer Center, discussed recent treatment progress in triple-negative breast cancer, emerging antibody-drug conjugates, and the need for clinical trials.

Her insights were based on discussions from the 2026 Bridging the Gaps in Breast Cancer Meeting.

The triple-negative breast cancer (TNBC) field has seen considerable progress in recent years, Natsuhara said, noting that she is excited about novel antibody-drug conjugates moving into the early-stage setting, where investigators are asking whether more patients can be cured. As these agents advance into the neoadjuvant and adjuvant settings, they will complicate treatment decisions in the metastatic setting, she noted, but the breast cancer paradigm has historically followed a paradigm of using the best therapies early. Natsuhara also highlighted bispecific antibody-drug conjugates (ADCs) and ADCs with novel targets and diverse payloads, a big area of need, as well as treatment approaches like targeted radioligand therapy.

Given how much is changing in the field, trials should be considered at every point of therapy change for patients with TNBC, Natsuhara said. In the first-line setting, more studies are expected as patients treated per the phase 3 KEYNOTE-522 trial (NCT03036488) regimen of pembrolizumab (Keytruda) plus chemotherapy develop metastatic disease, she noted. In the second-line setting, emerging data suggest that sequencing ADCs with the same payload does not appear to work, so therapies must be chosen carefully, and oncologists should look for trial options that can both generate practice-informing data and improve patient care, according to Natsuhara.

Finding those trials has been a challenge, Natsuhara acknowledged. She said that artificial intelligence tools have helped match patients to available studies, and that academic oncology centers are working to build relationships with community oncologists to streamline referrals so that patients can access trials regardless of where they live. Correlative studies with laboratory-based colleagues are also needed to understand resistance and identify new biomarkers, she said.

Natsuhara concluded by highlighting that the Bridging the Gaps meeting brings leaders together to confront shared clinical questions and define the next steps in trial and drug development.