Investigation of the prevalence of HER2-ultralow and the effects of HER2 status (HER2-null vs. HER2-ultralow) on survival in HER2-negative early-stage breast cancer
Clinical and Translational Oncology, cilt.28, sa.3, ss.924-933, 2026 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 28 Sayı: 3
- Basım Tarihi: 2026
- Doi Numarası: 10.1007/s12094-025-04095-6
- Dergi Adı: Clinical and Translational Oncology
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, EMBASE, MEDLINE, DIALNET, Health Research Premium Collection (ProQuest)
- Sayfa Sayıları: ss.924-933
- Anahtar Kelimeler: Breast cancer, Early-stage, HER2-ultralow, HER2 status
- Sağlık Bilimleri Üniversitesi Adresli: Evet
Özet
Purpose: Investigation of ‘HER2-ultralow’ prevalence and the effects of HER2 status (HER2-null vs. HER2-ultralow) on prognosis in patients with early-stage (non-metastatic) breast cancer. Methods/patients: This single-center, retrospective study analyzed 424 patients with early-stage, CerbB2 immunohistochemistry (IHC) score 0 breast cancer. Pathological re-review classified tumors as HER2-ultralow (≤ 10% of tumor cells with faint, incomplete membrane staining) or HER2-null (no staining). The cohorts were stratified by estrogen receptor (ER) status into ER + (≥ 1%) and triple-negative breast cancer (TNBC) groups. Results: This study included 235 ER + and 189 TNBC patients. HER2-ultralow frequency was 30.6% (n = 72) in the ER + group and 18% (n = 34) in the TNBC group. In the ER + group, higher Ki67 and increasing stage were associated with worse 5 year disease-free survival (DFS) (p = 0.006 and p < 0.001, respectively), while HER2 status had no significant effect on 5-year DFS (p = 0.269). In the TNBC group, HER2-ultralow patients had worse 5-year DFS than HER2-null patients (67% vs. 74.1%, p = 0.048). In multivariate analysis, HER2 status was a statistically significant prognostic factor [(HR: 0.34 (0.145–0.841), p = 0.019)]. Despite a numerically worse 5 year overall survival (OS) rate in HER2-ultralow versus HER2-null patients (73.2% vs. 79.5%), the difference was statistically insignificant (p = 0.114). Conclusions: In TNBC, HER2-ultralow was a poor prognostic factor associated with inferior 5 year DFS compared to HER2-null, while no difference was observed in the ER + cohort. These findings suggest that HER2-ultralow status may identify a TNBC subgroup that warrants novel therapies, such as T-DXd, although validation in larger studies is needed.