HER2: a never ending story

Access to anti-HER2 agents for breast cancer is restricted to patients with HER2-positive tumours. However, the promising activity of novel anti-HER2 antibody–drug conjugates in patients with tumours with HER2-low-positive expression 1 Modi S Park H Murthy RK et al. antitumor activity and safety of trastuzumab deruxtecan in patients with HER2-low-expressing advanced breast cancer: results from a phase Ib study. J Clin Oncol. 2020; 38: 1887-1896 Google Scholar , 2 Banerji U van Herpen CML Saura C et al. Trastuzumab duocarmazine in locally advanced and metastatic solid tumours and HER2-expressing breast cancer: a phase 1 dose-escalation and dose-expansion study. Lancet Oncol. 2019; 20: 1124-1135 Google Scholar is challenging the dichotomy of HER2-positive versus HER2-negative breast cancer. Clinical and molecular characteristics of HER2-low-positive breast cancer: pooled analysis of individual patient data from four prospective, neoadjuvant clinical trialsOur results show that HER2-low-positive tumours can be identified as new subgroup of breast cancer by standardised IHC, distinct from HER2-zero tumours. HER2-low-positive tumours have a specific biology and show differences in response to therapy and prognosis, which is particularly relevant in therapy-resistant, hormone receptor-negative tumours. Our results provide a basis for a better understanding of the biology of breast cancer subtypes and the refinement of future diagnostic and therapeutic strategies. Full-Text PDF