When the binary “HER2-positive vs HER2-negative” model collapsed under the weight of DESTINY-Breast04 and 06, the real work began: deciding who should receive trastuzumab deruxtecan (T-DXd), when to leapfrog chemotherapy, and how to keep quality of life front-and-center. In this interactive Live from Seattle stream, translational researcher & clinician Dr. V.K. Gadi and high-volume breast oncologist Dr. Fengting Yan wrestle with that nuance in front of a virtual audience. Drawing on SABCS sub-analyses, ASCO 2025 biomarker updates, and their own experience and anecdotes, they outline a decisional playbook that blends disease-burden triage, endocrine-resistance patterns, and the evolving spectrum of HER2 testing from IHC 3+ to “ultralow” 0.1 %.

Whether you manage trials, beds, or databases, this hour distills the fast-moving ADC landscape into pragmatic rules of thumb and flags the knowledge gaps that still separate evidence from art.

Topics include:

• HER2 re-imagined: from a rigid binary to a four-tier lexicon (positive, low, ultralow, zero) and why pathologists now add “ultralow” to reports.

• DESTINY-Breast04 vs 06 head-to-head: why chemo-naïve, HR-positive patients doubled objective response (57 % vs 32 %) and what that means for first post-endocrine standard of care.

• Disease-burden triage: T-DXd first for “angry livers” and visceral-crisis lung mets; oral agents still reasonable for indolent bone-only progressors.

• Endocrine exhaustion vs sub-optimal use: ESR1 mutation, shrinking ER staining, and ≤6-month PFS as triggers to skip another endocrine line and go straight to an ADC.

• Sequencing before traditional chemo: weighing physician-choice capecitabine against IV T-DXd after DB-06 — and the lingering fear of closing off later options.

• Safety & survivorship: keeping ILD in check while troubleshooting weight-gain, nausea, and fatigue before cutting the dose.

• ADC-after-ADC Sandwich? emerging data on payload switching and why some clinicians are abandoning the “sandwich” doctrine to front-load the most active agents.

• Real-world evidence 2.0: how AI-curated registries are validating clinical-trial deltas across messy geographies and comorbidity spectra.

• Future watch-list: DB-09, NeoCARHP and biomarker-guided de-escalation trials, e.g. ATEMPT 2.0 that might finally limit indefinite therapy.

🎧 Like, share, and subscribe for more CHM Conversations that translate headline data into bedside decisions

#BreastCancer #HER2Low #Ultralow #TDXd #OncologyPodcast #CHMConversations

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Community Health Media (CHM) is your full service healthcare communications partner, combining our production expertise with targeted multi-channel campaigns. We connect companies and healthcare brands with key opinion leaders, patients, and consumers through compelling content and live experiences.

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