Biology-Driven Care and AI Tools Steer the Future of Breast Oncology

In this episode of Oncology Unplugged, host Chandler Park, MD, MSc, FACP, a medical oncologist at Norton Cancer Institute in Louisville, Kentucky, was joined by Jame Abraham, MD, FACP, the enterprise chairman of the Department of Hematology and Medical Oncology at Cleveland Clinic and a professor of medicine at the Cleveland Clinic Lerner College of Medicine in Ohio.

Their discussion centered on recent practice-changing advances in breast cancer, spanning treatment de-escalation, antibody-drug conjugates, and the growing role of artificial intelligence (AI) in oncology. Drs Park and Abraham first addressed findings from the phase 3 ASCENT-04 trial (NCT05382286), in which sacituzumab govitecan-hziy (Trodelvy) plus pembrolizumab (Keytruda) improved progression-free survival over physician’s choice of chemotherapy in the first-line setting in patients with PD-L1–positive metastatic triple-negative breast cancer. Dr Abraham offered guidance on management strategies for neutropenia and diarrhea associated with this combination.

The conversation then turned to treatment de-escalation, highlighting data from the phase 3 OPTIMA trial (ISRCTN42400492), which demonstrated that patients with high-risk, node-positive, hormone receptor–positive early breast cancer and low recurrence scores derived no benefit from adding chemotherapy to endocrine therapy. Dr Abraham underscored the biology-driven rationale for sparing chemotherapy and advocated for ovarian function suppression in high-risk premenopausal patients, citing data from the phase 3 SOFT (NCT00066690) and TEXT (NCT00066703) trials.

Drs Park and Abraham also examined the May 2026 FDA approvals of fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) for the treatment of patients with early HER2-positive disease, focusing on the results of the phase 3 DESTINY-Breast05 trial (NCT04622319), in which T-DXd reduced the risk of invasive disease or death vs ado-trastuzumab emtansine (Kadcyla). Dr Abraham detailed the importance of interstitial lung (ILD) disease monitoring with T-DXd use and highlighted the reassuring lack of added ILD risk with concurrent radiation that was seen in the trial.

Finally, the experts explored AI’s transformative potential in oncology, emphasizing the importance of clinician involvement in its development, tools like OpenEvidence, and takeaways from the Cleveland Clinic’s AI Summit for Healthcare Professionals, which took place in August 2026. Overall, Drs Park and Abraham affirmed that a patient-centered focus for cancer care should always ultimately guide treatment decisions.