Dr Traina on Integrating T-DXd and Biomarkers Into Early-Stage HER2-Positive Breast Cancer Care

“At the present time, no one tool is the perfect biomarker. What we’ll be working toward is some sort of integrated system and biomarker that helps us to best predict benefit from therapies.”

Tiffany A. Traina, MD, FASCO, a breast medical oncologist, vice chair of Outpatient Operations in the Department of Medicine, and section head of the Triple Negative Breast Cancer Clinical Research Program at Memorial Sloan Kettering Cancer Center, discussed how to incorporate new neoadjuvant and adjuvant fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu; DS-8201a) data into the treatment of patients with early-stage HER2-positive breast cancer, as well as the role of biomarkers in treatment selection.

Notably, her insights stemmed from discussions that took place at the 2026 Bridging the Gaps in Breast Cancer Meeting.

New agents and new indications for existing agents have been approved in breast cancer, generating considerable controversy about how to apply the data in practice, Traina said. For instance, in early-stage HER2-positive disease, the neoadjuvant phase 3 DESTINY-Breast11 trial (NCT05113251) showed dramatic pathologic complete response results with T-DXd followed by a taxane, trastuzumab (Herceptin), and pertuzumab (Perjeta; THP), vs dose-dense doxorubicin and cyclophosphamide followed by THP. The adjuvant phase 3 DESTINY-Breast05 trial (NCT04622319) also demonstrated great success with T-DXd in high-risk patients with residual disease after neoadjuvant therapy vs ado-trastuzumab emtansine (Kadcyla). The trials ran simultaneously, and now both datasets are available and contribute to uncertainty regarding how to incorporate both regimens into clinical practice, she explained.

Much of the discussion at the meeting centered on how biomarkers could help select patients who need an escalated regimen vs those who may benefit from treatment de-escalation, according to Traina. Traditional markers, such as imaging response to therapy and pathologic complete response, can guide treatment and identify an at-risk population that needs more therapy in the adjuvant setting, she noted. The meeting discussants also noted the importance of baseline molecular and tissue-based biomarkers and highlighted that circulating tumor DNA is a dynamic marker.Traina concluded that the field will work toward an integrated biomarker system to best predict benefit from therapy.