Clinical characteristics, metastasis patterns, and treatment outcomes of HER2-low breast cancer

Breast cancer (BC) is a heterogeneous disease, traditionally classified by hormone receptor and HER2 (human epidermal growth factor receptor 2) status. HER2-low, characterized by low HER2 expression without gene amplification, recently gained attention. While new therapies are promising, its clinical significance remains unclear. We analysed 241,510 BC patients diagnosed between 2000 and 2020 in Germany using data from the German Cancer Registry Group. HER2 status was determined using immunohistochemistry and fluorescence in situ hybridization results, and patients were classified as HER2-positive, HER2-low or HER2-zero. Clinical features, chemosensitivity and long-term outcomes - metastasis-free survival (MFS), recurrence-free survival (RFS), and overall survival (OS) - were analysed using Cox models. HER2-low comprised 42% of female and 47% of male patients, predominantly hormone receptor positive. Metastatic patterns in HER2-low and HER2-zero were similar but differed from HER2-positive, which showed more liver metastasis and multiple metastatic sites. HER2-positive showed worse MFS, RFS, and OS than HER2-zero and HER2-low subtypes. Pathological complete response (pCR) rates after neoadjuvant chemotherapy were highest in HER2-positive. HER2-low has higher hormone receptor positivity, distinguishing it from HER2-zero. While metastatic behaviour, treatment and long-term response in HER2-low were comparable to HER2-zero, the hormone receptor status seems to play a critical role in these outcomes.