#4.
Trans-RESPECT HER2DX Prognostic Value in Older Patients with HER2-Positive Early Breast Cancer: A Correlative Analysis from the RESPECT Phase III Trial Kazuki Nozawa1,2, Masataka Sawaki3, Yukari Uemura4, Naruto Taira5, Michiko Tsuneizumi6, Toshimi Takano7, Naomi Gondo8, Fumikata Hara9, Michiko Harao10, Mercedes Marín-Aguilera11, Patricia Villagrasa11, Aleix Prat11,12,13, Hiroji Iwata1 (1) Department of Advanced Clinical Research and Development, Nagoya City University Graduate School of Medical Sciences, (2) Department of Breast Surgery, Nagoya City University Graduate School of Medical Sciences, (3) Department of Breast Oncology, Nagoya Medical Center, (4) Biostatistics Section, Department of Data Science, Center for Clinical Sciences, Japan Institute for Health Security. (5) Department of Breast and Thyroid Surgery, Kawasaki Medical school, (6) Department of Breast Surgery, Shizuoka General Hospital, (7) Department of Breast Medical Oncology, The Cancer Institute Hospital of JFCR, (
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Background ➢HER2DX1), the first multigene assay specifically designed for HER2+ breast cancer, has demonstrated potential to guide treatment decisions. ➢However, its validation in the context of de-escalated chemotherapy regimens, including trastuzumab monotherapy, in older patients remains limited. ➢In the RESPECT trial (NCT01104935) 2), 1-year of trastuzumab monotherapy was shown to be a clinically meaningful adjuvant option compared to de-escalated chemotherapy and trastuzumab in older patients with HER2+ early breast cancer. ➢This exploratory analysis of HER2DX within the RESPECT trial (Trans-RESPECT study) aimed to evaluate the assay's prognostic value (NCT01104935). 1) Prat A, et al. EBioMedicine. 2022 Jan;75:103801. 2) Sawaki M, et al. J Clin Oncol. 2020; 38(32): 3743-3752.
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RESPECT trial 3-y DFS 92.4% vs. 95.3% Trastuzumab monotherapy approach may be considered a therapeutic option in the management of elderly patients. J Clin Oncol. 2020; 38(32): 3743-3752.
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HER2DX is based on 4 different gene signatures comprising 27 genes EBioMedicine. 2022; 75: 103801.
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Prognostic Value of the HER2DX Risk Score for Long-term Outcomes RFS Median follow-up 9.1 years OS Nozawa K, Sawaki M, et al. Nat Commun. 2025 Nov 4;16(1):9585. Statistically significant difference in OS was observed between the HER2DX low-risk and high-risk groups, whereas only a trend was observed for RFS.
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Prognostic Value of Individual HER2DX Biological Signatures and Composite Score Heatmap of percentile scores for immune, luminal, and proliferation signatures across 154 tumors profiled in Trans-RESPECT, illustrating biological heterogeneity. Boxplots showing the association between TIL levels and each HER2DX biological signature (IGG/Immune). Nozawa K, Sawaki M, et al. Nat Commun. 2025 Nov 4;16(1):9585.
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Conclusions • HER2DX provides long-term prognostic information in older patients with HER2+ early breast cancer. • When combined with the HER2DX pCR score, it may help identify individuals most likely and least likely to benefit from chemotherapy, supporting a more personalized approach to treatment in this understudied population. • Prospective trials are essential to validate its use for guiding treatment decisions, particularly for patients classified as HER2DX low risk. HER2DX may help identify candidates for de-escalation strategies,