Developing Story: The Trial That Dares to Say Cure with Dr. Lior Braunstein

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Live from Stage 4 | Episode #035| 06/30/2026 | Developing Story

GUESTS

Dr. Lior Z. Braunstein, MD is a board-certified radiation oncologist and physician-scientist who specializes in the treatment of localized and metastatic breast cancer. He serves as an Associate Attending in the Department of Radiation Oncology at the Memorial Sloan Kettering Cancer Center (MSKCC) in New York City.

Clinical & Academic Leadership

• Vice Chair Role: Appointed as the inaugural Vice Chair of Clinical AI, Informatics, and Digital Strategy for MSKCC Radiation Oncology.

• Program Director: Leads educational efforts as a Program Director within the department.

• Professional Memberships: Holds active memberships in ASTRO, ASCO, AACR, and NRG Oncology.

Education and Training

• Medical Degree: Harvard Medical School (Graduated 2011).

• Residency: Harvard Radiation Oncology Residency Program (Completed 2016).

Research Focus

Dr. Braunstein runs the Laboratory for Innovation in Breast Cancer (LANTERN) at MSKCC, focusing on clinical and translational research. His major research initiatives include: 

• The ARCHER Trial: Serving as a primary investigator for the ARCHER trial (Ablation and Resection for the Consolidation of Oligometastatic HER2+ Breast Cancer). This Phase II randomized study evaluates whether adding surgery and local radiation to standard drug therapies can eradicate resistant cancer cells and improve long-term outcomes in patients whose HER2-positive breast cancer has spread to a few small sites. 

• The HERO Trial: Leading the national NRG-BR008 (HERO) trial, a randomized study optimizing and safely minimizing radiation therapy for early-stage HER2-positive breast cancer patients. 

• Tattoo-less Radiation: Advancing surface-guided radiation therapy (such as AlignRT) to remove the need for permanent skin tattoos while improving clinical accuracy and patient experience

Quick Summary

Dr. Lior Braunstein, radiation oncologist at Memorial Sloan Kettering, joins Victoria Goldberg and Ellen Landsberger to discuss the ARCHER trial — a groundbreaking study combining surgery and ablative radiation with standard HER2-targeted therapy in patients with oligometastatic HER2-positive breast cancer. The goal: eradicate every last cancer cell before resistance can emerge.

Key Takeaways

1. 1. Radiation oncologists treat cancer; radiologists diagnose it. They're distinct specialties — radiation is a therapeutic tool, not just an imaging one.

   2. HER2-positive breast cancer is one of the best-understood cancers in oncology. Targeted therapies have transformed outcomes, but resistance eventually emerges in many patients.

   3. Cancer develops resistance by "shape-shifting" around drugs. The cells most likely to develop resistance are those in visible tumor sites — which is exactly what the ARCHER trial targets.

   4. Oligometastatic disease (5 or fewer metastases) may behave differently from widespread metastatic disease — and may be more amenable to aggressive, potentially curative treatment.

   5. The ARCHER trial adds surgery + ablative radiation on top of standard HER2-targeted therapy — nobody gets less than their current treatment.

   6. Previous trials failed to answer this question because they included all breast cancer subtypes. HER2-positive patients were too few to detect a meaningful signal. ARCHER focuses exclusively on HER2-positive disease.

   7. Treating only the primary tumor isn't enough — the ECOG-ACRIN 2108 trial showed no survival benefit from breast surgery alone. ARCHER addresses all visible sites simultaneously.

   8. "Cure" is a loaded word in oncology — not because it never happens, but because long follow-up has shown events can occur beyond the traditional 5-year mark.

   9. The ARCHER trial is for de novo oligometastatic HER2-positive disease — first diagnosis, 5 or fewer mets, no brain metastases, all sites safely treatable with radiation.

   10. AI is transforming clinical trial matching — helping ensure patients aren't missed simply because their clinician didn't have every trial top of mind during a busy clinic day.

   11. If successful, next steps include expanding to brain mets, other subtypes, and patients with metastatic recurrence — not just de novo stage IV.

The ARCHER Trial

The ARCHER trial (Ablation and Resection for the Consolidation of Oligometastatic HER2+ Breast Cancer) is a Phase II randomized study led by Principal Investigator Dr. Lior Zvi Braunstein of Memorial Sloan Kettering Cancer Center. The trial investigates whether adding local consolidation therapy (surgery and radiation) to standard systemic treatment improves outcomes for patients with newly diagnosed oligometastatic HER2-positive breast cancer.

Key Study Details

• Objective: To assess if consolidating all sites of initial disease (locoregional breast treatment + oligometastasis-directed therapy) improves progression-free survival (PFS) compared to continued systemic therapy alone

• Target Population: Patients with HER2-positive breast cancer that has spread to 1–5 discrete metastatic sites (oligometastatic), with no central nervous system (brain) involvement

• Study Arms:

  1. Control Arm: Standard of care HER2-directed systemic therapy (e.g., trastuzumab, pertuzumab, paclitaxel) .

  2. Intervention Arm: Standard systemic therapy plus local consolidation, including:

     • Surgery (lumpectomy or mastectomy) for the primary breast tumor.

     • Locoregional radiation therapy to the breast.

     • Stereotactic Body Radiation Therapy (SBRT) or resection for metastatic sites

• Hypothesis: Local consolidation may safely eradicate resistant cancer cells during a critical window, potentially leading to a cure or significantly delaying disease progression before resistant mechanisms develop

Eligibility Criteria

• Age: ≥18 years

• Disease Status: Newly diagnosed oligometastatic HER2+ breast cancer (≤5 lesions, no brain involvement) [

• Stability: Must have received drug therapy with no worsening of cancer in the last 3–12 months‍ ‍

• Function: Able to perform routine activities for >50% of waking hours (ECOG 0–2)

• Safety: No serious side effects from prior treatments; all metastatic sites must be safely treatable with SBRT or resection

Clinical Significance

Historically, HER2-positive breast cancer had poor outcomes, but modern targeted agents have made it the most favorable subtype, with 10–15% of metastatic patients living nearly a decade without progression 3. However, the disease is still considered treatable rather than curable. The ARCHER trial is the first oligometastatic study specifically focused on this subtype, aiming to determine if aggressive local therapy can seize a window to achieve a cure

Trial Identification

• ClinicalTrials.gov ID: NCT07053085

• Protocol Number: 25-145

• Lead Organization: Memorial Sloan Kettering Cancer Center

References

A Phase 2 Study of Surgery and Radiotherapy Plus Standard Treatment in People With Breast Cancer That Spread to a Few Sites

For more information, patients can contact Dr. Braunstein’s office at 201-775-7446