Kyoto first Red Cross hospital

Abstract Background: To assess recurrence risk in ER-positive, HER2-negative early breast cancer, multigene assays (MGAs) are useful in addition to clinicopathological factors. In Japan, Curebest™ 95GC was developed in 2011 and introduced clinically in 2013. Oncotype DX® was added to national health insurance in 2023. While adjuvant chemotherapy is often considered for patients classified as high-risk by any MGA, treatment decisions can be complex. Furthermore, breast cancers identified as high-risk by MGAs often exhibit higher pathological complete response (pCR) rates, suggesting increased sensitivity to chemotherapy. This study aimed to evaluate MGAs from two perspectives—prognostic prediction and NAC sensitivity—to inform individualized treatment strategies. Materials and Methods: We analyzed microarray gene expression data from public databases to identify patients with ER-positive, HER2-negative early breast cancer. In this study, Curebest™ 95GC, developed in Japan, was used post-analysis for research purposes only. Based on microarray expression data, we calculated PAM50, 21GC (Oncotype DX® surrogate analyses), EndoPredict (EP), and either 95GC or 155GC. In Study 1(n=555), we assessed the prognostic value of each MGA and evaluated recurrence risk based on the number of high-risk classifications. In study2(n=550), we evaluated the predictive value of each MGA for pCR rate and analyzed the relationship between NAC sensitivity and the combined assessment of the number of high-risk classifications treated with NAC. Results: In Study 1, all four MGAs (PAM50, 21GC, EP, and 95GC) significantly stratified DRFS between high- and low-risk groups (p =8.93e-08, 2.31e-08, 3.64e-07, and 9.25e-10), with comparable prognostic performance. Patients were grouped by the number of high-risk classifications. A 5-year DRFS of 97% was observed in patients with 0 high-risk classifications, compared to 66% in those with 4. Patients were further stratified into two groups: those with 0 or 1 high-risk classification and those with ≥2. The 0-1 group showed a 5-year DRFS of 96.7%, while the ≥2 group had a significantly worse prognosis at 79.0% (p=2.04e-11). The combined assessment provided better prognostic accuracy than any individual MGA alone. Notably, patients with only one high-risk result showed excellent outcomes, suggesting endocrine therapy alone may suffice. Conversely, those deemed low-risk by all MGAs may not require adjuvant chemotherapy.In Study 2, high-risk patients had significantly higher pCR rates across all MGAs. 155GC showed the strongest stratification (p=1.62e-08). Patients classified as high-risk by all four MGAs had significantly higher pCR rates than those with 0-3 high-risk classifications (p=9.37e-11). 95GC provides CEL files containing expression data for all 20,000 genes. This allows concurrent calculation of multiple MGAs, facilitating evaluation and reducing cost. Use of CEL files supports integrated MGA analysis, and may support precise personalized treatment. Conclusion: Combining four MGAs improves prediction over single MGAs. This integrated genomic approach offers a promising strategy to optimize individualized treatment in ER-positive, HER2-negative early breast cancer. Citation Format: M. Nishida, R. Tsunashima, N. Hirotani, S. Kitano, C. Matsui, S. Matsumoto, A. Watanabe, C. Kato, M. Morita, K. Sakaguchi, Y. Naoi. Integrated Prognostic and Chemotherapy Sensitivity Assessment Using Multiple Gene Assays in ER-positive, HER2-negative Early Breast Cancer [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS3-08-25.

<title>Abstract</title> Purpose Although image-enhanced endoscopy (IEE) is useful, its benefit over white light imaging (WLI) for the detection of superficial non-ampullary duodenal epithelial tumors (SNADETs) remains unclear. We evaluated whether narrow-band imaging (NBI) and texture and color enhancement imaging (TXI) could improve SNADET visibility compared to WLI under CO ₂ insufflation and underwater conditions. Methods We conducted a post-hoc analysis using a prospectively collected image database from patients with SNADET enrolled in a multicenter observational study. We used the EVIS X1 system with a GIF-H290Z or GIF-EZ1500 endoscope to compare the visibility scores for the recognition of SNADETs. We also measured the color difference (ΔE*), saturation difference (ΔC*), and lightness difference(ΔL*) between the tumor and background mucosa. Results We analyzed 50 lesions, comprising 46 intramucosal adenocarcinomas and 4 adenomas. Under CO ₂ insufflation, TXI provided a significantly higher visibility score than the WLI (2.7 ± 0.8 vs 2.5 ± 0.9, <italic>P</italic> = 0.002); however, no significant differences were observed between TXI and NBI (2.7 ± 0.8 vs 2.6 ± 0.7, <italic>P</italic> = 0.072). Underwater conditions yielded significantly higher visibility scores than CO ₂ insufflation across the three modes (WLI, 3.1 ± 0.6 vs. 2.5 ± 0.9, <italic>P</italic> &lt; 0.001; NBI, 2.9 ± 0.7 vs. 2.6 ± 0.7, <italic>P</italic> &lt; 0.001; TXI, 3.2 ± 0.5 vs. 2.7 ± 0.8, <italic>P</italic> &lt; 0.001). The ΔC* in TXI was significantly higher than that in WLI under CO ₂ insufflation (8.5 ± 6.0 vs 5.9 ± 3.9, <italic>P</italic> &lt; 0.001) and underwater condition (9.2 ± 5.6 vs 6.6 ± 3.5, <italic>P</italic> &lt; 0.001). Conclusion TXI significantly improved SNADET visibility compared to WLI under CO ₂ insufflation and underwater conditions, likely due to the increased saturation difference.

Weerda

Treating chronic hepatitis C virus infection with direct-acting antivirals (DAAs) results in a sustained virological response (SVR) in most cases, but hepatocellular carcinoma (HCC) can occur in some patients after achieving SVR. Thus, this study comprehensively assessed the risk factors associated with the development of HCC during long-term follow-up in patients who achieved SVR. Furthermore, we aimed to identify a group of patients without prior HCC treatment who are at extremely low risk for HCC long after achieving SVR. This retrospective cohort study included patients who achieved SVR after DAA therapy, and predictors contributing to the incidence of HCC were determined via Cox regression analysis. Specifically, we evaluated the factors contributing to the incidence of HCC among patients without previous HCC treatment later than 5 years after achieving SVR, and these were used to construct a predictive scoring system for HCC. Overall, 267 cases of HCC were observed during follow-up. Male sex, older age, previous HCC treatment before starting DAA therapy, excessive alcohol use, diabetes mellitus, elevated γ-GTP, low albumin, and low platelet count were independent predictors of HCC. Since previous HCC treatment strongly influenced the incidence of HCC after SVR, we further analyzed the risk factors for HCC among patients without previous HCC treatment. In that cohort, parameters at 5 years after achieving SVR that contributed to the incidence of HCC later than 5 years after SVR were an age of ≥ 70 years, diabetes mellitus (DM), and fibrosis-4 index(Fib-4) of ≥ 2.67. These three factors were used to create a scoring system, with scores of 0 to 3 predicting a 0.8%, 2.7%, 11.9%, and 28.8%, respectively, cumulative incidence rate of HCC later than 5 years after SVR. Using long-term follow-up data, we investigated the risk factors for HCC among patients who achieved SVR after DAA therapy. Previous HCC treatment strongly predicted HCC after SVR. Although this was a retrospective cohort study, among patients without previous HCC treatment, those younger than 70 years, without DM and with a Fib-4 index of < 2.67 had a very low risk of developing HCC later than 5 years after SVR.