HER2DX in older patients with HER2-positive early breast cancer: extended follow-up from the RESPECT trial of trastuzumab ± chemotherapy
Older adults with HER2-positive early breast cancer are underrepresented in clinical trials, and the benefit of chemotherapy in this population remains uncertain. We evaluated the HER2DX genomic assay within the randomized RESPECT trial (NCT01104935), which compared adjuvant trastuzumab with or without chemotherapy in patients aged 70-80 years. In this prespecified translational analysis (Trans-RESPECT), HER2DX scores were available for 154 patients. The HER2DX risk score classified 74.0% as low risk and 26.0% as high risk. Ten-year relapse-free and overall survival were higher in the low-risk group. HER2DX remained independently associated with overall survival in multivariable analysis. The HER2DX immune, luminal, and proliferation signatures that compose the risk score were also prognostic. While the HER2DX pCR score was not prognostic overall, exploratory subgroup analyses suggested a potential survival benefit from chemotherapy in the pCR-high group. HER2DX offers prognostic value and may guide chemotherapy use in older patients with HER2-positive early breast cancer. Clinical Trial Information NCT01104935.
Authors
- Michiko Harao (ORCID: https://orcid.org/0000-0002-3138-062X)
- Yukari Uemura (ORCID: https://orcid.org/0000-0002-3013-7775)
- Fara Brasó‐Maristany (ORCID: https://orcid.org/0000-0001-5440-9643)
- Peter J. Park (ORCID: https://orcid.org/0000-0001-9378-960X)
- Fumikata Hara (ORCID: https://orcid.org/0000-0001-8025-3494)
- Tatsuya Toyama (ORCID: https://orcid.org/0000-0003-4713-7795)
- Guillermo Villacampa (ORCID: https://orcid.org/0000-0003-4868-6585)
- Toshimi Takano (ORCID: https://orcid.org/0000-0002-8417-5291)
- Michiko Tsuneizumi
- Masataka Sawaki (ORCID: https://orcid.org/0000-0002-2927-9258)
- Charles M. Perou (ORCID: https://orcid.org/0000-0001-9827-2247)
- Naruto Taira (ORCID: https://orcid.org/0000-0003-4266-1117)
- Esther Sanfeliu (ORCID: https://orcid.org/0000-0002-7974-3346)
- Laia Paré (ORCID: https://orcid.org/0000-0002-4904-558X)
- Ana P. Vivancos (ORCID: https://orcid.org/0000-0003-2888-6512)
- Hiroji Iwata
- Patricia Villagrasa (ORCID: https://orcid.org/0000-0002-8662-3641)
- Wesley Buckingham (ORCID: https://orcid.org/0009-0006-4707-9803)
- Mercedes Marín‐Aguilera (ORCID: https://orcid.org/0000-0002-2205-3459)
- Aleix Prat (ORCID: https://orcid.org/0000-0003-2377-540X)
- Kazuki Nozawa (ORCID: https://orcid.org/0000-0002-0277-8196)
- Naomi Gondo
Institutions
- University of North Carolina at Chapel Hill (US)
- Jichi Medical University (JP)
- Kawasaki Medical School (JP)
- Breast Cancer Research Foundation (US)
- Nagoya City University (JP)
- National Center for Global Health and Medicine (JP)
- Vall d'Hebron Institut de Recerca (ES)
- Hospital Quirónsalud Barcelona (ES)
- National Sagamihara Hospital (JP)
- Cancer Clinic (US)
- Vall d'Hebron Hospital Universitari (ES)
- Aichi Cancer Center (JP)
- Shizuoka General Hospital (JP)
- The Cancer Institute Hospital (JP)
- Oryzon Genomics (Spain) (ES)
- Nagoya Medical Center (JP)
- Consorci Institut D'Investigacions Biomediques August Pi I Sunyer (ES)
- UNC Lineberger Comprehensive Cancer Center
- Universitat de Barcelona (ES)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-11-04
- DOI
- https://doi.org/10.1038/s41467-025-65599-x
- Citations
- 1
- Primary Topic
- HER2/EGFR in Cancer Research
- Type
- article
- Field-Weighted Citation Impact
- 1.05
Funders
- American Society of Clinical Oncology
- Chugai Pharmaceutical