Background: Hormone-receptor positive (HR+), early stage breast cancer patients (pts) are at risk for late ( > 5 year) distant recurrence (DR) and are now considered for extended (10 year) endocrine therapy (EET) to prevent late disease relapse. Approximately 50% of all HER2+ breast cancer pts are also HR+. Clinical trials investigating the benefit of EET to reduce late DR have included HER2+/HR+ pts, but subset analyses in comparison to HER2-/HR+ have been limited. Breast Cancer Index (BCI) is a gene expression based assay validated to 1) assess risk of late DR, and 2) predict benefit from EET using the endocrine response biomarker HoxB13/IL17BR (H/I). This study compared BCI results and clinicopathologic factors in HER2+/HR+ vs HER2-/HR+ breast cancer. Methods: Consecutive cases with known HER2 status (N = 1182) submitted for BCI clinical testing were analyzed for pt characteristics and BCI reporting rates according to HER2 status. Fisher’s test was used to compare results between subgroups. Results: 12% of BCI testing was conducted on HER2+/HR+ pts. Tumor size distribution was similar for HER2+ and HER2- cohorts (P = 0.9). In converse, the HER2+ cohort was comprised of a higher proportion of grade 3 (51% vs 17%; P < 0.001) and ER+/PR- tumors (24% vs 7%; P < 0.001). In regards to risk of late DR, 3 times more tumors were classified as BCI High-Risk in the HER2+ cohort compared to the HER2- cohort (59% vs 19%, P < 0.001; Table 1). Twice as many HER2+ were predicted to benefit from EET compared to the HER2- cohort (High H/I; 69% vs 38%, P < 0.001; Table 1). Conclusions: BCI classifies a higher proportion of HER2+/HR+ tumors into a high-risk group compared to those that are HER2-/HR+, yet a subset of HER2+ tumors are classified as low-risk. Additionally, a significant proportion of the HER2+ cohort was predicted to benefit from ETT. Further studies to validate the ability of BCI to predict benefit of EET in HER2+/HR+ pts are warranted.