Correlation of HER2 levels expression through HER2 mRNA PCR vs immunohistochemistry (IHC) in hormone receptor positive (HR+)/HER2 negative (HER2−) early breast cancer

Abstract Purpose To evaluate the correlation between HER2 expression levels measured by HER2 mRNA using Oncotype DX and by immunohistochemistry (IHC) in hormone receptor-positive (HR+) and HER2-negative (HER2−) early breast cancer. In addition, we assessed whether low HER2 expression is associated with distinct clinicopathological characteristics and prognosis in our series. Methods We conducted a retrospective study that included 500 patients diagnosed with stage I–III HR+/HER2− breast cancer who underwent surgery and had Oncotype DX recurrence score determined between 2009 and 2023 at Hospital Clínico San Carlos, Madrid, Spain. HER2 mRNA levels obtained through Oncotype DX were compared across IHC groups (HER2 0+, HER2 1+, HER2 2+/ISH-negative). Event-free survival (EFS) was analyzed according to HER2 expression. Results Although HER2 mRNA levels increased with higher IHC HER2 categories, variability and overlap were observed between subgroups. Median Oncotype DX recurrence scores also rose slightly across HER2 IHC groups but did not reach statistical significance. EFS did not differ between HER2 expression levels. Conclusions We found that HER2 mRNA measurement by Oncotype DX provides a quantitative approach to assess HER2 expression. However, its results overlap within traditional IHC categories. While HER2-low classification may have therapeutic implications for new antibody–drug conjugates, its prognostic relevance appears limited. Further studies are needed to improve HER2 quantification methods for improved clinical decision-making.