HER2-low breast cancer: a new concept in breast cancer treatment strategy

HER2, a human epidermal growth factor, being activated by amplification, is a negative prognostic factor in breast cancer. HER2 is the target of anti-HER2 antibodies (Trastuzumab, Pertuzumab.). For more than 10 years, breast cancers have been classified into HER2 positive and HER2 negative. However, the advent of new cytotoxic drugs combined with anti-HER2 antibodies, such as TDM1 or trastuzumab deruxtecan, have shown very promising therapeutic activity in patients with low HER2 expression breast cancer. These new therapeutic perspectives encourage a better identification of low HER2 tumours in order to identify patients who could benefit from them. Thus, the classification of breast tumours evolves to individualize HER2-negative tumours (score 0), HER2-positive tumours (score 3+ and 2+ amplified) and HER2-low tumours (scores 1+ and 2+ not-amplified). HER2-low tumours are common and represent more than half of all breast cancers. To identify these HER2-low tumours, pathology laboratories should not change their usual technique calibrated according to ASCO/CAP and GEFPICS recommendations. Until more clinical data about response to these new treatment strategies are available, GEFPICS does not require pathologists to identify this HER2-low category. Nevertheless, this designation will allow clinicians to identify patients whose tumours fall into this category in the very short term and offer them new treatment options.