The impact of Staging investigations in HER2-low, low risk patients

Background: 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 early breast cancer (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 • 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%) (p = 0.65). A total of 205 patients with confirmed HER2-low status (IHC 1+ or 2+ with negative FISH) were further analyzed regarding staging procedures and follow-up examinations. Due to suspicious findings during initial staging, additional imaging was required in 30 cases (6.4%). In total, 466 staging tests were performed in the HER2-low cohort, resulting in 40 (9.1%) follow-up examinations. Metastases were confirmed in three patients (0.8%) following these additional investigations, corresponding to a positive predictive rate of 6.4% in this group. Conclusion: Distant metastases are rare in HER2-low early breast cancer (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.