ER staining levels affect HER2 staining and heterogeneity

Purpose This study explored the relationship of ER expression levels with HER2 staining properties and heterogeneity and discussed the differences in HER2 assessment caused by the 2018 ASCO/CAP guideline updates from that of the 2013 version. Methods HER2-positive breast cancer was divided into three groups of the high hormone receptor expression (LH-high) group, low expression (LH-low) group, or negative (NLH) group to (1) compare differences in the percentage of the HER2 IHC test score of 2 + based on the 2013 ASCO/CAP guideline and in the intratumor heterogeneity of HER2 expression for breast cancer with an IHC score of 3 + among these groups, (2) compare the HER2/CEP17 ratio and the average HER2 copy number, and classified ISH groupings according to the 2018 ASCO/CAP guideline algorithm. Results (1) Of 244 HER2-positive breast cancers, the cases with a HER2 IHC score of 2 + (n = 54, 22.1%) were significantly more common in the LH-high group (n = 45, P < 0.001). The frequency of heterogeneity was low (n = 25, 10.2%) for the HER2 score of 3 + (n = 190, 77.9%), and significantly higher in the LH-high group (n = 19, 76%, P = 0.002). (2) In a HER2 IHC score of 2 + , Group 2 which is deemed HER2 negative according to the revised 2018 ASCO/CAP guideline was observed in 17 (39.5%) out of 43 cases, of which 16 cases (94.1%) were in the LH-high group. Conclusions The LH-high group is a heterogeneous group largely consisting of heterogeneous cases with HER2 IHC scores of 2 + or 3 + . NLH, in contrast, is a homogenous group.