1MO Prognostic and biologic significance of HER2-low expression in early breast cancer

Approximately 50% of HER2-negative breast cancers (BC) show HER2-low expression. It is unclear however whether BC should be considered an individual biologic entity, prognostically distinct from HER2-zero BC. Data were collected institutional database including all consecutive patients with who underwent surgery at Dana-Farber Brigham Cancer Center 1/2016 to 3/2021. Tumors defined as if they had a HER2 IHC score 1+ or 2+ negative FISH, and 0. Clinicopathologic characteristics disease outcomes compared between the two cohorts. 5235 eligible for analysis; 4429 estrogen receptor (ER)+, 67 ER-low (1-9%), 739 ER-negative. Hormone receptor(HR)-expression was significantly more common among (89.9% vs 80.9%, p<0.001). Most other clinicopathological differences explained by different rate HR+ tumors. When evaluated continuous variable, ER expression associated (p<0.001), tumors increased progressively increasing (Table). Among receiving neoadjuvant chemotherapy (n=657), those higher pCR rates (27% 17%, p=0.002). However, statistical difference lost when separately analyzing (8% 14%, p=0.078), (25% 38.9%, p=0.46), without (6.9% 10.4%, p=0.277), TNBC (30.8% 35.4%, p=0.40) adjusting confounders. No in disease-free survival overall observed depending on expression.Table: 1MOProportion versus according tumor subtype expressionTNBCER-low (1-9%)ER-moderate (10-49%)ER-high (50-95%)ER-very-high (>95%)HER2-low40%46%55%58%62%HER2-zero60%54%45%42%38% Open table new tab Our results do not support interpretation subtype. continuously level are enriched cases may confound prognostic analyses.