The Impact of Staging Investigations in HER2-Low, Low-Risk Patients.

Introduction: Staging examinations have historically not been standard practice in low-risk early breast cancer (EBC). This study aimed to assess the frequency, modalities, and clinical implications of staging diagnostics in this population, including the incidence of additional imaging, false-positive findings, and metastatic rates, with a comparative focus on HER2-low subgroups. Methods: This retrospective single-center cohort study included all patients diagnosed with low-risk EBC at the University Medical Center Freiburg between 2017 and 2023. Low-risk criteria comprised clinical stage T1/2, node-negative (N0), hormone receptor-positive (HR+), HER2-low (IHC 1+/2+ with negative FISH) or HER2-negative (IHC 0) status, and asymptomatic presentation. Demographic, clinicopathological, and staging data were analyzed, including modalities and frequency of staging diagnostics, incidence of subsequent imaging/biopsies triggered by indeterminate findings, false-positive rates, and metastatic outcomes. HER2 status was classified as: HER2-low: IHC 1+ or 2+ with FISH-negative and HER2-negative: IHC 0 without membrane staining. Comparative analyses examined how metastatic rates and the use of staging procedures differed between the HER2-low subgroups. Results: Of the included patients, 158 (43.5%) had a HER2 IHC 0, 153 (42.2%) had a HER2 IHC 1+, and 52 (14.3%) had a HER2 IHC 2+ with a negative FISH test. The overall risk of distant metastases was 0.8%. Among patients with a HER2 IHC 1+, the metastasis rate was 1 (0.7%); in the HER2 IHC 2+ group, no metastases were observed (0.0%); and in the HER2 IHC 0 group, the metastasis rate was 2 (1.3%) ( Conclusion: Distant metastases are rare in HER2-low EBC. Overall, staging tests should not be routinely performed in this patient population. This study found no significant difference in the rate of metastasis between patients with a HER2 IHC 0 and those with a HER2-low status.