Clinicopathological features and prognosis of breast cancer with low HER2 status evaluated by fluorescence <i>in situ</i> hybridization

Although trastuzumab deruxtecan improves the prognosis of patients with HER2-low breast cancer, the characteristics and prognostic value of low HER2 status remains to be elucidated. A prospective database of patients with clinical stage I to III breast cancer who underwent surgery between September 2012 and October 2022 at Teikyo University Hospital (Tokyo, Japan) were analyzed. HER2 was evaluated using fluorescence <i>in situ</i> hybridization assay, and HER2-low and HER2-negative was defined as HER2/CEP17 ratio ≥1.0, and <1.0, respectively. The median age and Ki67 score of the 1,024 patients were 56.0 years (range, 23.0-93.0 years) and 15.0% (range, 0.5-99.0%), respectively. Overall, 908 (88.7%) patients were hormone receptor positive. Among all patients, 902 (88.1%) had HER2-low tumors and 122 (11.9%) had HER2-negative tumors. Positive rates for estrogen receptor (ER) and progesterone receptor (PgR) were significantly higher in HER2-low compared with HER2-negative patients [ER: 804 (89.1%) patients vs. 99 (81.1%) patients, P=0.021; PgR: 723 (80.1%) patients vs. 86 (70.5%) patients, P=0.023]. The median Ki67 score was significantly lower in HER2-low compared with HER2-negative patients (14.5 vs. 18.5%; P=0.013). With a median follow-up time of 46.2 months, the overall survival (OS) was significantly improved in HER2-low compared with HER2-negative patients (97.4 vs. 96.7%; P=0.029). Multivariate logistic regression analyses revealed that HER2-low status was not an independent factor for OS. The findings of the present study suggest that HER2-low status may not have a significant association with prognosis, despite a significant association between Ki67 and hormone receptor expression.