Filling in the Gaps of Examining Human Epidermal Growth Factor Receptor 2 (HER2)-Low and HER2-Ultralow in Breast Cancer: Clone Choice, Sample Size, and Reevaluating Scores Made on Archived Samples.

Context.—: Human epidermal growth factor receptor 2 (HER2)-low breast carcinoma is a clinical entity that has targeted therapy.

Objectives.—: To evaluate the effect of antibody clone/sample size on HER2 status and reinterpret archived HER2-stained slides following current guidelines.

Design.—: 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.

Results.—: 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.

Conclusions.—: 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.