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HER2 Expression and Axillary Metastasis in Treatment-Naïve Early Breast Cancer
Ferit Aydin1, Cemil Yuksel2, Cuneyt Akyuz2
1Department of Surgical Oncology, Ankara Etlik City Hospital, Yenimahalle, Ankara, Turkey.
Breast Cancer (Dove Medical Press)
|July 14, 2026
Summary
In early-stage breast cancer, human epidermal growth factor receptor 2 (HER2)-low status does not independently predict axillary metastasis risk. Lymphovascular invasion is the strongest predictor of metastasis in treatment-naïve patients.
Area of Science:
- Oncology
- Breast Cancer Research
- Molecular Diagnostics
Background:
- The clinical significance of HER2-low breast cancer, especially in early-stage, treatment-naïve patients, is debated.
- Neoadjuvant therapy can alter tumor biology and nodal status, necessitating evaluation of upfront surgery cohorts.
- The HER2-ultralow subgroup's impact on axillary metastasis requires investigation.
Purpose of the Study:
- To evaluate the association between HER2 expression (including HER2-ultralow) and axillary metastasis in hormone receptor-positive, early-stage breast cancer patients.
- To determine if HER2 status predicts sentinel lymph node (SLN) positivity in treatment-naïve patients.
- To identify predictors of axillary metastasis in this cohort.
Main Methods:
- Retrospective analysis of 407 hormone receptor-positive, early-stage breast cancer patients undergoing upfront surgery (2017-2023).
- Categorization into HER2-ultralow (IHC 0), HER2-low (IHC 1+ or 2+/FISH-negative), and HER2-positive (IHC 3+ or 2+/FISH-positive) groups.
- Comparison of SLN positivity rates and multivariable logistic regression/ROC analyses for metastasis predictors.
Main Results:
- Similar SLN positivity rates across HER2-ultralow (29.0%), HER2-low (30.6%), and HER2-positive (31.3%) groups.
- HER2 expression was not an independent predictor of SLN positivity.
- Lymphovascular invasion (LVI) was the strongest determinant of axillary metastasis (OR=5.42), followed by tumor size and proliferative activity.
Conclusions:
- HER2 expression is not independently associated with axillary metastasis risk in treatment-naïve, early-stage breast cancer patients undergoing upfront surgery.
- Lymphovascular invasion, tumor size, and proliferative activity are the primary determinants of axillary involvement.
- Further research with longer follow-up is needed to confirm survival differences.