Clinical and molecular characteristics of HER2-low-positive breast cancer: pooled analysis of individual patient data from four prospective, neoadjuvant clinical trials

2,310 patients with HER2-non-amplified primary breast cancer treated in GeparSepto, GeparOcto, GeparX and GAIN-2 with prospective central HER2 testing were pooled. 1,098 (47.5%) were HER2-low-positive (IHC 1+ or 2+/ISH-negative) and 1,212 HER2-zero; 703 (64.0%) of HER2-low versus 445 (36.7%) of HER2-zero tumours were hormone receptor-positive, so 395 of 1,162 hormone receptor-negative tumours (34.0%) were HER2-low. pCR was lower in HER2-low tumours overall (29.2% versus 39.0%) and in the HR-positive subgroup but not in the HR-negative subgroup (50.1% versus 48.0%). HER2-low patients had longer three-year disease-free (83.4% versus 76.1%) and overall survival (91.6% versus 85.8%), with the differences seen in HR-negative tumours (DFS 84.5% versus 74.4%; OS 90.2% versus 84.3%).