298P Association of luminal-androgen receptor (LAR) subtype with low HER2 in triple-negative breast cancer

Low level of HER2+ breast cancer, a subset of HER-2 negative, accounts for about 50-60% of breast cancer. A recent publication highlighting the improved survival outcomes with trastuzumab deruxtecan in this group has raised the need to redefine low HER2+ breast cancer in the context of molecular characterization. In triple-negative breast cancer (TNBC), we compared molecular TNBC subtype, PAM50 subtypes, and clinical-pathological characteristics between the low HER2 and zero HER2 groups. A study population included two cohorts with early TNBC. The adjuvant cohort consisted of 199 TNBC patients who underwent upfront surgery, while the neoadjuvant cohort comprised 124 TNBC patients treated with neoadjuvant chemotherapy (NAC). Transcriptome analysis was conducted in the adjuvant cohort to determine the TNBC molecular subtype and PAM50 types. Tumor-infiltrating lymphocyte (TIL) levels, PD-L1, and Ki67 expression were evaluated in both cohorts, along with recurrence-free survival (RFS) and event-free survival (EFS) investigations in each cohort. In 199 patients with transcriptome analysis, 66 (33.2%) had low HER2 disease, while 133 (66.8%) had zero HER2 tumors. The rates of luminal androgen receptor (LAR) and HER2-E subtypes were 13.1% (26/199) and 7.0% (14/199), respectively. Comparing the two groups, low HER2 tumors showed higher rates of LAR (22.7% vs. 8.5%, p=0.006) and HER2-E (15.2% vs. 3.3%, p=0.016), while other characteristics such as TIL, PD-L1, ROR-P score, and Ki67 did not differ between the two groups. In the neoadjuvant cohort, 31 (25.0%) had low HER2 disease while 93 (75.0%) had zero HER2 tumors, and there were no significant differences in TIL, PD-L1, and Ki67 expression between the two groups. Furthermore, low HER2 status did not significantly affect RFS and EFS in either cohort. Low HER2 status in TNBC is distinctly associated with enriched LAR and HER2-E subtypes. However, other characteristics such as TIL, PD-L1, and Ki67 expression, as well as survival outcomes, were found to be similar between the two groups.