Internodal HER2 heterogeneity of axillary lymph node metastases in breast cancer patients

Determination of human epidermal growth factor receptor 2 (HER2) status is important for adequate treatment of breast cancer (BC) patients. The novel HER2 gene protein assay (GPA) is particularly convenient, as it allows the simultaneous assessment of HER2 protein expression and gene amplification at individual cell level. Here we investigated the frequency of internodal HER2 heterogeneity in axillary lymph node macrometastases of BC patients and compared HER2 status between primary breast tumor and its metastases. We included a total of 41 female patients operated between 2014 and 2015 for primary BC with axillary lymph node macrometastases. Representative paraffin blocks of metastatic lymph nodes were sectioned and the slides were stained using the GPA in 38 BC cases. GPA results were assessed according to the ASCO/CAP 2013 criteria. We analyzed 12586 individual tumor cells, 120 cells per section of each metastatic lymph node. HER2 status differed between the primary tumor and its metastases in 5/38 cases (13.2%). In patients with at least two metastatic nodes, the HER2 status of lymph node metastases was only slightly different in 4/23 cases (17.4%). Our results indicate rare but substantial differences in HER2 status between primary breast tumor and its axillary lymph node metastases that may direct the choice and outcomes of targeted therapy in BC patients. The impact of the rare and subtle internodal HER2 heterogeneity evidenced in this study remains uncertain. Determining the HER2 status of lymph node metastases in BC seems to be rational, but assessing a limited number of metastatic nodes may be sufficient.