Clinical application of the HM-1000 image processing for HER2 fluorescence in situ hybridization signal quantification in breast cancer.

BACKGROUND: Accurate quantification of human epidermal growth factor receptor 2 (HER2) gene amplification is important for predicting treatment response and prognosis in patients with breast cancer. Fluorescence in situ hybridization (FISH) is the gold standard for the diagnosis of HER2 status, particularly in cases with equivocal status on immunohistochemistry (IHC) staining, but has some limitations of non-classical amplifications and such cases are diagnosed basing on additional IHC and FISH. This study investigated the clinical utility of a novel super-resolution fluorescence microscopy technique for the better FISH signal visualization and HER2 FISH classification. METHODS: Fourteen breast cancer tissue samples were retrospectively collected between September 2018 and February 2022, and FISH HER2 signal quantification was evaluated by determining the HER2/chromosome 17 centromere (CEP17) ratio and the number of HER2 signals per nucleus in super- versus conventional-resolution images. RESULTS: Super-resolution images maintained the same overall HER2 diagnosis from routine, but HER2 FISH amplification changed negative to monosomy in two cases. Two Letrozole non-response relapses coincided to monosomy samples. The median number of HER2 signals per nucleus was 7.5 in super-resolution images and 4.0 in conventional-resolution images in HER2-positive samples and 2.8 and 2.1 signals per nucleus, respectively, in HER2-negative samples. CONCLUSIONS: Super-resolution images improved signal visualization, including a significant difference in the number of countable HER2 and CEP17 signals in a single nucleus compared with conventional-resolution images. Increased accuracy of signal quantification by super-resolution microscopy may provide clinicians with more detailed information regarding HER2 FISH status that allows to better FISH classification such as HER2-low samples.

Cost and Budget Impact Analysis of an Accurate Intraoperative Sentinel Lymph Node Diagnosis for Breast Cancer Metastasis.

BACKGROUND: Conventional intraoperative sentinel lymph node biopsy (SLNB) in breast cancer (BC) has limitations in establishing a definitive diagnosis of metastasis intraoperatively, leading to an unnecessary second operation. The one-step nucleic amplification assay (OSNA) provides accurate intraoperative diagnosis and avoids further testing. Only five articles have researched the cost and cost effectiveness of this diagnostic tool, although many hospitals have adopted it, and economic evaluation is needed for budget holders. OBJECTIVE: We aimed to measure the budget impact in Japanese BC patients after the introduction of OSNA, and assess the certainty of the results. METHODS: Budget impact analysis of OSNA on Japanese healthcare expenditure from 2015 to 2020. Local governments, society-managed health insurers, and Japan health insurance associations were the budget holders. In order to assess the cost gap between the gold standard (GS) and OSNA in intraoperative SLNB, a two-scenario comparative model that was structured using the clinical pathway of a BC patient group who received SLNB was applied. Clinical practice guidelines for BC were cited for cost estimation. RESULTS: The total estimated cost of all BC patients diagnosed by GS was US$1,023,313,850. The budget impact of OSNA in total health expenditure was -US$24,413,153 (-US$346 per patient). Two-way sensitivity analysis between survival rate (SR) of the GS and OSNA was performed by illustrating a cost-saving threshold: y â‰… 1.14x - 0.16 in positive patients, and y â‰… 0.96x + 0.029 in negative patients (x = SR-GS, y = SR-OSNA). Base inputs of the variables in these formulas demonstrated a cost saving. CONCLUSION: OSNA reduces healthcare costs, as confirmed by sensitivity analysis.