Re: “Evolution of low HER2 expression between early and advanced-stage breast cancer”

In a phase 3, multicentre, open-label, randomised trial, trastuzumab deruxtecan (TD) was superior to the standard of care trastuzumab emtansine in patients with HER2-positive metastatic breast cancer (mBC) previously treated with trastuzumab and a taxane [ [1] Cortés J. Kim S.B. Chung W.P. Im S.A. Park Y.H. Hegg R. et al. DESTINY-Breast03 trial investigators. Trastuzumab deruxtecan versus trastuzumab emtansine for breast cancer. N Engl J Med. 2022 Mar 24; 386 (PMID:35320644): 1143-1154https://doi.org/10.1056/NEJMoa2115022 Crossref PubMed Scopus (232) Google Scholar ]. Then, a phase 3 trial with HER2-low mBC patients (defined as 1+ and 2+ by immunohistochemistry [IHC] or negative by in situ hybridisation [ISH]) who had received previous lines of chemotherapy was performed [ [2] Modi S. Jacot W. Yamashita T. Sohn J. Vidal M. Tokunaga E. et al. Trastuzumab deruxtecan in previously treated HER2-low advanced breast cancer. N Engl J Med. 2022 Jul 7; 387 (Epub 2022 Jun 5. PMID:35665782): 9-20https://doi.org/10.1056/NEJMoa2203690 Crossref PubMed Scopus (360) Google Scholar ]. In this trial TD resulted in significantly longer progression-free and overall survival than the physician's choice of chemotherapy. Evolution of low HER2 expression between early and advanced-stage breast cancerEuropean Journal of CancerVol. 163PreviewLow human epidermal growth factor receptor 2 (HER2) expression is emerging as an actionable biomarker for the treatment of breast cancer (BC) with novel anti-HER2 drugs. However, the evolution of this biomarker during the course of disease is still poorly characterised, and controversial data exist on its prognostic implications. Full-Text PDF Response to letter entitled: Re: “Evolution of low HER2 expression between early and advanced-stage breast cancer”European Journal of CancerVol. 179PreviewWe thank Dr. Bravaccini et al. for their thoughtful comments on our work [1] on the evolution of HER2-low expression between early and advanced breast cancer. The authors highlight some important challenges existing in the diagnosis of HER2-low breast cancer, an entity still under definition. Full-Text PDF