Human epidermal growth factor receptor 2 (HER2)–low breast carcinoma is a clinical entity that has targeted therapy.
To evaluate the effect of antibody clone/sample size on HER2 status and reinterpret archived HER2-stained slides following current guidelines.
We collected 86 estrogen-receptor+/HER2− breast carcinoma core needle biopsy (CNB) samples with archived slides stained with HER2 (HercepTest) and for Oncotype DX (ODX) assay. These slides were scored by 3 pathologists (consensus score) and then compared to the reported scores. The CNB and excisional biopsy (EB) samples were stained with 4B5. We performed a 3-way comparison between CNB-4B5, CNB-HercepTest, and EB-4B5. The mRNA values were abstracted from the ODX report. The mRNA values were compared with the EB-4B5 scores (semiquantitative [H-score] and categorical [zero, 1+, and 2+] system), the consensus score of CNB-HercepTest, and then with the consensus scores of CNB-4B5.
Upon rescoring the archived CNB-HercepTest slides, 45.3% were discordant; 12 of 19 (63.2%) reported as 1+ were HER2-zero. The discordance rate between CNB-4B5 and EB-4B5 was 24.4%; between CNB-4B5 and CNB-HercepTest, 59.3%; and between CNB-HercepTest and EB-4B5, 62.8%. The mRNA values correlated with EB-4B5 when using the H-score (P = .003) or the categorical system (zero, 1+, 2+) (P = .008), and with CNB-4B5 (P = .002), but did not correlate with CNB-HercepTest.
The discordance of HER2 staining depended on the sample size and antibody clone. Tissue stained with 4B5 (CNB or EB), but not with CNB-HercepTest, correlated with mRNA values.
Author notes
Alqassim and Yasmeen contributed equally to the project
Khoury serves as a pathology faculty advisor for Daiichi Sankyo and AstraZeneca; he is also a collaborator with Cepheid. The other authors have no relevant financial interest in the products or companies described in this article.
Supplemental digital content is available for this article. See text for hyperlink.