HER2 mRNA Score From Quantitative ERBB2 mRNA Expression of Oncotype Dx

As novel human epidermal growth factor receptor-2 (HER2) and drug conjugates have proven to be effective treatments for both HER2-positive breast cancer (BC) and HER2-low BC, the need to develop more accurate methods to quantify HER2 status has increased. We compared the correlation between the HER2 mRNA score (HS), obtained using the Oncotype DX (ODX) test, and HER2 immunohistochemistry (IHC) to verify the accuracy of HER2 quantification and its correlation with clinicopathologic characteristics. We retrospectively collected ODX test data from 1524 estrogen-receptor positive, HER2-negative patients with BC. No significant differences in clinicopathologic characteristics, including ODX Recurrence Score (RS), were observed between HER2-0 and HER2-low BC. The median HS value of the HER2-low subgroup was significantly higher than that of the HER2-0 subgroup ( P <0.001) and increased significantly between the 4 subgroups classified by HER2 IHC ( P <0.001). The receiver operating characteristic curve showed acceptable utility in distinguishing HER2-0 from HER2-low (area under the curve=0.76) and HER2-null and HER2-ultralow subgroups (area under the curve=0.81), but the overlap between subgroups was also prominent. After defining 8.9 as a suboptimal cutoff mRNA score, multivariate analysis revealed that low Ki-67 (<20%) and RS (≤25) were statistically associated with higher HS (>8.9), whereas progesterone receptor negativity, high Ki-67, high nuclear grade, lower HS, and older age (>50 y) were statistically associated with high RS. Our study revealed that HS is significantly associated with HER2 IHC results and clinicopathologic parameters other than HER2 IHC.