Low doesn’t mean no.

When the breast pathology report reads HER2 low, that’s the same thing as HER2 negative, right? Not so fast, my friend. HER2 IHC of 0 or 1+ is considered negative while 3+ is positive. 2+ is equivocal and considered positive or negative depending on the results of FISH. This study sought to determine if tumors with low HER2 expression have different clinical behavior than those that are completely negative among patients treated on four prospective neoadjuvant therapy trials. Among all patients, a neat one-third were HER2+, one-third HER2- but hormone receptor (HR)+, and one-third triple-negative. These groups had very different clinical outcomes. HER2 low tumors, which were associated with HR+ and low grade, had lower rates of pathologic complete response (pCR) to neoadjuvant therapy (29%) compared to HER2 zero tumors (39%) which were more likely HR- and high grade. However, survival was longer for HER2 low (92% at 3 years) than for HER2 zero (86%). | Denkert, Lancet Oncol 2021