Kazuki Nozawa, Masataka Sawaki, Yukari Uemura, Michiko Tsuneizumi, Toshimi Takano, Naomi Gondo, Fumikata Hara, Michiko Harao, Tatsuya Toyama, Naruto Taira, Ana Vivancos, Charles M. Perou, Esther Sanfeliu, Fara Brasó‐Maristany, Peter J. Park, Wesley Buckingham, Laia Paré, Guillermo Villacampa, Mercedes Marín‐Aguilera, Patricia Villagrasa, Aleix Prat, Hiroji Iwata
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.