Clinicopathological features and prognosis of breast cancer with low HER2 status evaluated by fluorescence in situ 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 in situ 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.