Surgical oncology · 2026
Predictive factors and prognostic significance of HER2-low early breast cancer with long-term follow-up.
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Niwa Yuka, Terada Mitsuo, Wanifuchi-Endo Yumi, Fujita Takashi, Asano Tomoko, Kawaguchi Hidetoshi, Nozawa Kazuki, Matsumoto Nana, Isogai Ayaka, Kawahara Hikaru, Mizumoto Marie, Toyama Tatsuya
Аннотация
BACKGROUND: Human epidermal growth factor receptor type2 (HER2)-low breast cancer has emerged as a clinically relevant subtype with novel HER2-targeted therapies. This study aimed to investigate the clinicopathological features and prognostic implications of HER2-low status in patients with early breast cancer undergoing long-term follow-up.
METHODS: We retrospectively analyzed patients with HER2-negative early breast cancer who underwent surgery between 2003 and 2022. We investigated clinicopathological factors associated with HER2-low status and the clinical impacts of HER2-low/zero status on disease-free survival (DFS), distant DFS (DDFS), and overall survival (OS) according to hormone receptor (HR) status using univariate and multivariate analyses.
RESULTS: Among 3663 patients with early breast cancer, we identified 2519 HER2-negative patients (HER2-low 57%, HER2-zero 28%). HER2-low status was associated with high estrogen-receptor (ER) positivity (Allred score 8) and less mucinous histology, but there was no association with progesterone receptor (PgR) expression. HER2-low status also tended to be associated with pre/perimenopausal status and higher nuclear grade (≥2), but not with tumor size or lobular/metaplastic type. Pathological complete response rates after neoadjuvant chemotherapy were comparable between HER2-low (18.9%) and HER2-zero (21.6%), with no survival differences. HER2 status (low vs. zero) was not significantly associated with DFS, DDFS, or OS, and had no prognostic impact in patients with either HR-positive or -negative disease.
CONCLUSION: HER2-low breast cancer was characterized by distinct biological features, including high ER positivity (especially Allred score 8) without PgR association, but did not confer a prognostic advantage over HER2-zero disease. HER2-low status may reflect biological heterogeneity that could be relevant when interpreting treatment response rather than serving as an independent prognostic marker.
METHODS: We retrospectively analyzed patients with HER2-negative early breast cancer who underwent surgery between 2003 and 2022. We investigated clinicopathological factors associated with HER2-low status and the clinical impacts of HER2-low/zero status on disease-free survival (DFS), distant DFS (DDFS), and overall survival (OS) according to hormone receptor (HR) status using univariate and multivariate analyses.
RESULTS: Among 3663 patients with early breast cancer, we identified 2519 HER2-negative patients (HER2-low 57%, HER2-zero 28%). HER2-low status was associated with high estrogen-receptor (ER) positivity (Allred score 8) and less mucinous histology, but there was no association with progesterone receptor (PgR) expression. HER2-low status also tended to be associated with pre/perimenopausal status and higher nuclear grade (≥2), but not with tumor size or lobular/metaplastic type. Pathological complete response rates after neoadjuvant chemotherapy were comparable between HER2-low (18.9%) and HER2-zero (21.6%), with no survival differences. HER2 status (low vs. zero) was not significantly associated with DFS, DDFS, or OS, and had no prognostic impact in patients with either HR-positive or -negative disease.
CONCLUSION: HER2-low breast cancer was characterized by distinct biological features, including high ER positivity (especially Allred score 8) without PgR association, but did not confer a prognostic advantage over HER2-zero disease. HER2-low status may reflect biological heterogeneity that could be relevant when interpreting treatment response rather than serving as an independent prognostic marker.