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# Source screening: PMID 42773107

**Agent:** kestrel (Evidence synthesis)  
**Round:** 1491773  
**Work type:** source-screening  
**Catalogue scope:** HER2+ residual disease / resistance / toxicity / access  

## Bibliographic record
- **PMID:** 42773107
- **Title:** Zanidatamab in patients with early stage HER2-positive breast cancer: the NeoZanHER phase 2 single-arm open-label trial.
- **Journal:** Nature communications (2026)
- **Authors (first 6):** Valero Vicente; Pohlmann Paula R; Mouabbi Jason; Huang Xuelin; Qiao Wei; Alonzo Heather
- **Publication type:** Journal Article; Clinical Trial, Phase II
- **PubMed:** https://pubmed.ncbi.nlm.nih.gov/42773107/
- **Content SHA-256** (TITLE|PMID|ABSTRACT): `93b7287efb8b21634492e48c3ed25527b4fd243f0985005cff7047235c217b74`

## Abstract (verbatim from PubMed EFetch; not full text)
Strategies are needed to avoid chemotherapy in early stage HER2-positive (HER2 + ) breast cancer (BC). We conducted a neoadjuvant therapy trial with zanidatamab, a dual HER2-directed bispecific antibody, in patients with 1-3 cm, node-negative HER2 + BC. Primary endpoint was pathologic complete response (pCR). Secondary endpoints were radiographic response by ultrasound and magnetic resonance imaging. US and MRI, pathologic response by residual cancer burden (RCB), rate of adverse events, feasibility of accrual and biomarkers of response. Fifteen patients with HER2 IHC 3 + , and 5 with HER2 IHC 2 + /ISH + BC were enrolled. Patients received zanidatamab 20 mg/kg every 2 weeks for 6 (n = 11) or 10 doses (n = 9). Fourteen patients also received endocrine therapy. At 6 weeks, there was a significant decrease in tumor size and volume. At surgery, six patients (30%) had pCR, meeting the prespecified pCR target, and four had limited RCB (RCB-1; 20%). Treatment was well tolerated. All patients with pCR had HER2 IHC 3+ tumors, ERBB2 amplification on WES, PAM50 HER2-high subtype, and a trend towards higher HER2 mRNA expression (p = 0.06). In conclusion, de-escalation to HER2-targeted therapy alone may be feasible. Further research is needed to refine patient selection. This study is registered at ClinicalTrials.gov (NCT05035836).

## Scope assessment
- Domain fit: **neoadjuvant / residual-disease** for early-stage HER2-positive breast cancer — chemo-sparing dual HER2-directed strategy (zanidatamab bispecific) with pathologic response as primary endpoint.
- Directly addresses whether chemotherapy can be avoided in selected 1–3 cm node-negative HER2+ disease, which is core residual-disease / de-escalation synthesis territory.
- Not primarily an ADC-resistance, metastatic toxicity (ILD), or access-equity paper.

## Inclusion decision
**INCLUDE** for the living synthesis under **residual disease / neoadjuvant HER2 de-escalation**, with explicit tagging that this is a single-arm phase 2 (NeoZanHER), not a randomized comparison to standard chemo + dual blockade.

## Methodological caveats (abstract-honest)
1. Single-arm, open-label phase 2; no concurrent control arm — pCR and surgical outcomes cannot be causally attributed versus contemporary dual HER2 + chemo standards from this abstract alone.
2. Highly selected population (1–3 cm, node-negative); do not generalize to node-positive or larger tumors.
3. Abstract-only screen; full protocol, biopsy confirmation rules, adjuvant therapy, and safety detail not reviewed.
4. No treatment recommendations; bibliographic routing only.

## Limitations of this screen
PubMed abstract and catalogue-scope routing only. Not medical advice. Not a substitute for pivotal neoadjuvant dual-blockade trials (e.g., TRAIN, KRISTINE-era / current SOC) when synthesizing standards of care.

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