# Clinical and molecular characteristics of HER2-low-positive breast cancer: pooled analysis of individual patient data from four prospective, neoadjuvant clinical trials

Source: https://onco.cc/key-papers/paper-denkert-her2-low-pooled-neoadjuvant-lancet-oncol-2021/  
OnCo record `paper-denkert-her2-low-pooled-neoadjuvant-lancet-oncol-2021` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Among 2,310 patients in four German neoadjuvant trials, 34% of hormone receptor-negative tumours were HER2-low; they responded to chemotherapy as often as HER2-zero tumours but had better three-year survival.

## Summary

2,310 patients with HER2-non-amplified primary breast cancer treated in GeparSepto, GeparOcto, GeparX and GAIN-2 with prospective central HER2 testing were pooled. 1,098 (47.5%) were HER2-low-positive (IHC 1+ or 2+/ISH-negative) and 1,212 HER2-zero; 703 (64.0%) of HER2-low versus 445 (36.7%) of HER2-zero tumours were hormone receptor-positive, so 395 of 1,162 hormone receptor-negative tumours (34.0%) were HER2-low. pCR was lower in HER2-low tumours overall (29.2% versus 39.0%) and in the HR-positive subgroup but not in the HR-negative subgroup (50.1% versus 48.0%). HER2-low patients had longer three-year disease-free (83.4% versus 76.1%) and overall survival (91.6% versus 85.8%), with the differences seen in HR-negative tumours (DFS 84.5% versus 74.4%; OS 90.2% versus 84.3%).

## Fields

- Kind: Key paper
- Last checked: 2026-09-24
- Journal: The Lancet Oncology
- Year: 2021
- DOI: 10.1016/S1470-2045(21)00301-6
- Authors: Denkert C, Seither F, Schneeweiss A, et al.
- Findings: HER2-low in 395 of 1,162 hormone receptor-negative tumours, 34.0%.; pCR in HR-negative disease 50.1% HER2-low versus 48.0% HER2-zero.; HR-negative HER2-low: three-year DFS 84.5% versus 74.4%, OS 90.2% versus 84.3%.
- What it means: The trial-grade HER2-low share for TNBC is about a third, and the survival difference hints that HER2-zero triple-negative disease is the more aggressive group.
- Caveats: Pooled trial populations with different regimens.; Survival data available for 1,694 patients.

## Sources

- Denkert et al., Lancet Oncol 2021: HER2-low-positive disease in 2,310 patients from four neoadjuvant trials: https://doi.org/10.1016/S1470-2045(21)00301-6
- PubMed: https://pubmed.ncbi.nlm.nih.gov/34252375/

## Connected records

- biomarkers: [HER2-low (IHC 1+ or IHC 2+/ISH-negative)](https://onco.cc/biomarkers/her2-low-ihc/)
- cancers: [Early triple-negative breast cancer](https://onco.cc/cancers/tnbc-early/), [HER2-low and HER2-ultralow metastatic breast cancer](https://onco.cc/cancers/her2-low-metastatic-breast-cancer/), [Triple-negative breast cancer (TNBC)](https://onco.cc/cancers/tnbc/)
- targets: [HER2](https://onco.cc/targets/her2/)
- companies: [German Breast Group (GBG)](https://onco.cc/companies/gbg/)
- terms: [HER2-low and HER2-ultralow](https://onco.cc/terms/her2-low/), [Pathologic complete response (pCR)](https://onco.cc/terms/pcr/)
- people: [Carsten Denkert](https://onco.cc/people/carsten-denkert/), [Sibylle Loibl](https://onco.cc/people/sibylle-loibl/)
- journals: [The Lancet Oncology](https://onco.cc/journals/lancet-oncology/)

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